Repetitive Activation Patterns and Focal Impulses Identification and Ablation in Persistent AF Using the RHYTHMFINDER-192
Phase: NA
Conditions: Persistent Atrial Fibrillation
Sponsor: Biosense Webster, Inc.

 
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CLINICAL INVESTIGATION PROTOCOL 
 
 
 
 
 
 
 
 
 
 
RAPID-AF: Repetitive Activation Patterns and Focal Impulses 
Identification and Ablation 
in Persistent AF using the RHYTHMFINDER-192 
 
 
Sponsor: 
BIOSENSE WEBSTER, INC. 
 
3333 Diamond Canyon Road 
 
Diamond Bar, CA 91765 
 
 
 
Protocol number: 
CF-171 
 
Protocol Version Date:   
Version 2.0 -16 September, 2016 
 
 
 
History of Changes 
 
 
Version Date 
Description 
 
Version 1.0 – 10 November 2015 
 
Original document 
 
Version 2.0 – 16 September, 2016 
 
Updated protocol design 
 
 
 
 
The RHYTHMFINDER™ 192 Catheter or
 RF-192
 is for investigational 
device use only 
and is not commercially available anywhere in the world. 
‘(RAPID-AF)’ 
is an internal 
Biosense Webster project 
name and other than as used in the present clinical 
investigation, 
is not intended for any other external use. The final commercial or 
trade name of the RHYTHMFINDER™ 192 Catheter may be different.

 
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Repetitive Activation Patterns and Focal Impulses Identification and Ablation in 
Persistent AF using the RHYTHMFINDER-192 
 
RAPID-AF (“CF-171”) 
 
Clinical Investigation 
Number 
CF-171 
Clinical Investigation 
Name 
RAPID-AF 
Revision 
Version 2.0 
Date 
September 16, 2016 
 
Sponsor 
Biosense Webster, Inc. 
3333 Diamond Canyon Road 
Diamond Bar, CA 91765 
Tel +1 909-839-8500 
Fax +1 909-839-8804 
Contacts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Whereas, the Clinical Study is sponsored by Biosense Webster Inc.,  
Responsibilities for the conduct of this clinical study have been transferred in EMEA to 
Johnson and Johnson Medical NV/SA with registered offices at Leonardo Da Vincilaan 
15, 1831 Diegem, Belgium. 
 
Responsibilities for the conduct of this clinical study, have been transferred in Canada 
to Johnson & Johnson Medical products, a devision of Johnson & Johnson Inc., 200 
Whitehall Drive, Markham, Ontario, Canada L3R 0T5 
The sponsor maintains an updated list of principal investigators, sites and institutions 
and Contract Research Organizations (if applicable). The definitive list shall be 
integrated in the study report. 
 
 
 

 
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INVESTIGATOR SIGNATURE PAGE 
 
I have read the protocol and agree: 
 To conduct this clinical trial in accordance with the design and specific provisions of this 
protocol. 
 To await REB/IRB/EC-positive opinion for the protocol and informed consent as well as 
approval from the relevant Competent Authorities before initiating enrollment into the 
clinical trial. 
 To ensure that the requirements for obtaining informed consent are met and to obtain 
informed consent from subjects before their enrollment in the clinical trial. 
 To provide copies of the protocol and all pertinent information to all individuals 
responsible to me who assist in the conduct of this study. 
 To provide sufficient and accurate financial disclosure and update information if any 
relevant changes occur during the investigation and for 1 year following the completion of 
the clinical trial. 
 To collect and record data as required by this protocol and case report forms. 
 To maintain the confidentiality of all information received or developed in connection with 
this protocol. 
 To conduct this trial in accordance with 21 CFR Part 812 and ISO: 14155-2011 Standards 
and any other applicable local laws and regulations. 
 To permit trial-related monitoring, audits, REB/IRB/EC review, and regulatory 
inspection(s) by providing direct access 
to source data/documents. 
 To prepare annual, final adverse effect reports as required 
by this protocol. 
 To maintain clinical trial documentation for the period of time required. 
 To report all adverse events/incidents within the specified timeframe to Biosense 
Webster. 
 To report all serious adverse events/incidents immediately but no later than 3 calendar 
days after becoming aware of the event of occurrence to Biosense Webster; enter them 
into the EDC system. 
 To adhere to the publication policy of Biosense Webster for data collected during this clinical 
trial. 
 
 
 
 
 
 
Signature of Principal Investigator 
Date 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 

 
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PROTOCOL SYNOPSIS 
 
 
Sponsor 
Biosense 
Webster, 
Inc. 
3333 Diamond Canyon Road 
Diamond Bar, CA 91765 
Tel +1 909-839-8500 
Fax +1 909-839-8804 
 
Protocol 
Title 
 
Repetitive 
 
Activation 
Patterns and Focal Impulses Identification and 
Ablation 
in Persistent 
AF using the RHYTHMFINDER-192 
Abbreviated 
Title 
 
 
RAPID-AF 
Study Purpose 
The purpose of this study is to assess safety and effectiveness of the 
RHYTHMFINDER™ 192 Catheter in conjunction 
with the 
CARTOFINDER™ (CF) Algorithm when used for treatment of Persistent 
Atrial Fibrillation (PsAF). 
Study Devices 
RHYTHMFINDER basket catheter (Investigational) 
CARTOFINDER™ workstation (CE-mark) 
CARTO® 3 with CARTOFINDER™ module (CE-mark) 
 
Scope and study 
centers 
Geographic involvement may include centers worldwide, mainly 
Europe and Canada. Approximately 
6 to 10 centers 
worldwide 
will 
participate 
Study Population 
All subjects with persistent AF who are scheduled to undergo a clinically-
indicated ablation procedure for management of their persistent AF will 
be the target population for screening. 
Study Design 
The study will enroll approximately 40-70 subjects. 
 
Subjects will undergo CARTOFINDER™ 
guided ablation 
(CFGA) followed 
by PVI.  
Subjects 
will have follow-up visits at 7 days, 3, 6 and 12 months 
post-
procedure. 
Subjects where no CF ablation target is identified on the baseline 
CARTOFINDER™ map using the RHYTHMFINDER™ 192 Catheter, will exit 
the study after 7 day follow up. 
Study Duration Approximately 20 months 
(8 months recruitment, 12 months follow-up) 

 
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Study Endpoints 
 
Effectiveness 
 Acute success defined as: Rate of conversion of Atrial Fibrillation 
to Normal Sinus Rhythm 
or Atrial Tachycardia, after CFGA and PVI 
(without cardioversion) 
 Procedural success defined as: Conversion 
of Atrial Fibrillation to 
Normal Sinus Rhythm 
or Atrial Tachycardia after CFGA and PVI, 
with or without the need for cardioversion 
 Rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm 
or 
Atrial Tachycardia, after CFGA only (before PVI and without 
cardioversion) 
 Freedom from documented symptomatic AF/AT/AFL recurrence 
(episodes ≥ 30 seconds on an arrhythmia monitoring device) post 
the 3-month blanking period 
through 
the 12-month 
follow 
up. 
 Incidence of PVI (entrance block) after adenosine/isoproterenol 
challenge 
 Change of intra-cycle length from pre-CFGA to post-CFGA and 
post-PVI 
Safety 
 Incidence of early-onset primary adverse events within 7 days of 
the ablation procedure. 
 Incidence of study device and procedural related SAEs during 
follow-up period (12M) 
 Incidence of all SAEs during follow-up period (12M) 
 Incidence of study device and procedure related adverse events 
 

 
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Other Study 
Assessments 
 Number of identified CF ablation targets 
 Max #of active RF 192 electrodes during initial mapping 
procedure 
 AAD use post the 3-month blanking period 
 
 Incidence of repeat ablation procedures for AF post the 3 month 
blanking period 
 Procedural data: 
o All target sites for RF lesion application 
 Location of ablation targets 
 Number of RF applications per target 
 Total RF duration per application 
o RF ablation parameters (including but not limited to: 
power, contact force, impedance, flow rate, temperature)  
o Total fluoroscopy time and dose 
o Total procedure, mapping and ablation time 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study 
Inclusion 
Criteria 
Subjects 
must meet the following inclusion criteria: 
1. Age > 18 years. 
2. Patients who have signed the Patient Informed Consent Form 
(ICF) 
3. Scheduled to undergo a clinically-indicated catheter ablation 
procedure 
for treatment 
of 
a. persistent atrial fibrillation (defined as continuous atrial 
fibrillation that is sustained beyond seven consecutive 
days). 
b. drug-resistant atrial fibrillation. (failed 1 or more class I or 
III antiarrhythmic drugs) and demonstrating Persistent AF 
(requiring drugs or electrical shock to terminate AF) 
4. In AF at the time of the baseline CARTOFINDER™ Map 
(spontaneous) 
5. Left Atrium (LA) must demonstrate sufficient electrical activity to 
allow for the identification 
of ablation targets. 
6. Able and willing to comply with all pre-, post-, and follow-up 
testing and requirements (e.g. patients not confined by a court 
ruling) 

 
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Study Exclusion 
Criteria 
Subject who meet any of the following exclusion criteria are not 
eligible 
for enrollment. 
1. Paroxysmal Atrial 
Fibrillation 
2. Continuous 
AF > 12 months 
(1-Year) (Longstanding 
Persistent AF) 
Subjects previously diagnosed as Long Standing Persistent 
(LSP) but have demonstrated the ability to maintain Normal 
Sinus Rhythm for >30 days after cardioversion and have not 
been in AF greater than 1 year at the time of the procedure 
remain eligible for inclusion.  
3. Previous ablation procedure for PsAF (defined as ablations 
involving more than only PV isolation) 
4. Patients with a left atrial size >55 mm (echocardiography, 
parasternal 
long axis 
view). 
5. Inability to restore sinus rhythm for 30 seconds or longer in the 
opinion 
of the investigator. 
6. Significant congenital anomaly or medical problem that in the 
opinion of the investigator would preclude enrollment in this 
study. 
7. Atrial arrhythmia patients with structural atrial disease such as a 
prior history of atriotomy from prior atrial surgery, presence of an 
atrial septal defect, and/or presence of an atrial septal closure 
patch. 
 

 
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8. History of or current blood clotting or bleeding abnormalities, 
contraindication to systemic anticoagulation (i.e., heparin, 
warfarin, dabigatran, or a direct thrombin inhibitor). 
9. significant pulmonary disease, cardiac surgeries, unstable angina, 
uncontrolled heart failure, acute illness or systemic infection, or 
any other disease or malfunction that would preclude treatment 
in the opinion 
of the investigator. 
10. Current enrollment 
in a study evaluating 
another 
device or drug. 
11. A complex arrhythmia secondary to electrolyte imbalance, 
thyroid 
disease, 
or reversible 
or non-cardiac 
cause. 
12. Any cardiac surgery within the past 60 days (2 months) (includes 
PCI) 
13. Subjects that have ever undergone valvular cardiac surgical 
procedure (i.e., ventriculotomy, atriotomy, and valve repair or 
replacement 
and presence 
of a prosthetic 
valve) 
14. Prior ICD or pacemaker 
implanted 
15. Presence of intramural thrombus, tumor or other abnormality 
that precludes 
catheter 
introduction 
or manipulation. 
16. Presence 
of a condition 
that precludes 
vascular 
access. 
17. Subject has a contra-indication to the device under study per the 
IFU 
18. Women of child bearing potential whom are pregnant, lactating, 
or planning 
to become 
pregnant 
during 
the course 
of the trial. 
Treatment, 
Follow-up 
Schedule and  
Data Elements 
Baseline/Pre-procedure 
Assessments: 
 Demographics& NYHA 
 Medical 
history  
 Arrhythmia 
history 
 Cardiovascular medication history including 
anticoagulation 
regimen 
 ECG (12-lead) 
 CHADS-VASC2 score 
 Imaging (using standard detection techniques) for 
atrial size and 
thrombus detection 
 INR (before procedure), when applicable 
 Pregnancy 
test (pre-menopausal 
women only) 
 
Subjects who sign the informed consent form and who meet all 
inclusion and no exclusion criteria at screening/baseline will undergo 
a CARTOFINDER™ (CF) map using the RHYTHMFINDER™ 192 Catheter 
 

 
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Procedural Flow 
1. Baseline CARTOFINDER™ 
(CF) Mapping  
 Fast Anatomical Mapping (FAM) of the Right Atria (RA) using the 
commercially available THERMOCOOL® SMARTTOUCH™ Catheter 
and/or SMARTTOUCH® SF Catheter. 
 Baseline CF (map) recording of the RA using the RHYTHMFINDER™ 
192 Catheter 
 FAM map of the Left Atria (LA) using the THERMOCOOL® 
SMARTTOUCH™ 
Catheter and/or SMARTTOUCH® SF Catheter 
 Baseline CF (map) recording of the LA using the 
RHYTHMFINDER™ 192 Catheter 
 
2. CF Baseline Map Analysis 
 Analysis of the baseline CF map 
 Ablation Targets (FI/RAP) identification: 
 Identify areas with ablation targets including focal 
impulse (FI) or repetitive activation patterns (RAPs) 
 If an ablation target is identified, the subject will 
receive CFGA followed by PVI and be followed 
up until 12 months post procedure 
 If no CF ablation target is identified, the subject 
will be treated per investigator’s standard of 
care  and followed up until 7 days post 
procedure   
 
3. Procedure for CARTOFINDER™ Guided Ablation 
 Confirm identified ablation targets on the Baseline CF map 
 Ablate areas using the THERMOCOOL® 
SMARTTOUCH™ or 
SMARTTOUCH® SF Catheter identified by the CARTOFINDER™  map 
o If a post CFGA map is performed on the ablated atrium(a), 
analysis of the post-CFGA CF map for the existence of 
ablation targets should be performed 
 Complete above steps until one of the following conditions is met: 
o No further 
ablation 
targets 
are identified 
on the CF Map 
o Subject achieves normal sinus rhythm or an atrial tachycardia 
The final decision to not further ablate remaining RAP/FIs 
regardless of above criteria being met or not, remains at 
investigator’s discretion 
 After performing any CFGA, a CF map may be created at the 
investigator’s discretion, but is not required 
 If subject is in AF (or other arrhythmia) after CFGA, no cardioversion 
is permitted. RF192 catheter must not remain in the subject (being 
deployed in the atrium) for cumulative duration greater than 1.5 
hours (90 mins)  
 

 
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4. PVI Ablation  
 PVI ablation after CFGA is required for all subjects 
 Perform PVI* via Wide Area Circumferential Ablation (WACA) per 
your (institution’s) 
standard 
of care (SOC). 
 Perform entrance block confirmation 
 In case NSR is achieved through PVI, no further ablations are 
permitted other than to complete the PVI. 
 In case AT is achieved, additional ablations are permitted to 
ablate the Atrial Tachycardia at the investigator’s discretion. 
 In case AFL is achieved, the placement of additional RF lesions 
(i.e.. Linear lesions at the cavotricuspid isthmus) is at the 
discretion of the investigator  
 Perform a final CF Map** within same atrium(a) in which 
baseline map was collected, using the RHYTHMFINDER™ 192 
Catheter 
 AT: 
once achieved, 
one “post” ablation 
map is required 
 NSR: “post” ablation map is at the discretion of the investigator  
 If subject is in AF/AFL/AT, cardioversion may be performed ONLY 
after completing PVI. 
 
Prophylactic ablation of empirical sites is not allowed per protocol. 
All linear lesions require confirmation of conduction block by pacing 
and/or mapping maneuvers 
 
 
 

 
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Follow-up Schedule 
 
Post-Procedure -Discharge: 
 Adverse Events Procedural complication collection and 
notification 
 Arrhythmia 
assessment 
 Electrocardiogram 
(12-lead 
ECG) 
 Cardiovascular 
medication 
and anti-coagulation 
therapy 
 
Follow-up visit at 7-Day Post-Procedure (Clinic Visit or 
Telephone 
visit): 
 Arrhythmia 
assessment 
 Medical/hospitalization 
assessment 
 Adverse Events 
assessment and notification 
 Concomitant cardiovascular medication and anti-
coagulation therapy changes 
 
Follow-up visits at 3 months, 6 months and 12 Months (Clinic 
visit): 
 Medical 
and hospitalization assessment 
 Concomitant cardiovascular medication and anti- coagulation 
therapy 
 Arrhythmia 
recurrence, 
if observed 
 Electrocardiogram 
(12-lead 
ECG) 
 Arrhythmia Monitoring (Holter Monitoring) 
 Adverse 
Event 
assessment 
and notification 
 

 
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TABLE OF CONTENTS 
 
1  ABBREVIATIONS .................................................................................................................................. 
17 
2  INTRODUCTION .................................................................................................................................. 
18 
2.1  Background ................................................................................................................................. 
18 
2.2  Clinical Investigation Overview .................................................................................................. 
18 
2.3  Device Description 
...................................................................................................................... 
19 
2.3.1  
CARTOFINDER™ Workstation with 4D LAT Algorithm ........................................................ 
19 
2.3.2  CARTO® 3 EP Navigation System with CARTOFINDER™ Module 
........................................ 
19 
2.3.3  
RHYTHMFINDER™ 192 Catheter (D-1367-05-SI and D-1367-06-SI) 
................................... 
20 
2.3.4  
Ablation catheters ............................................................................................................... 
20 
3  CLINICAL INVESTIGATION OBJECTIVES .............................................................................................. 
21 
4  CLINICAL INVESTIGATION OUTCOME MEASURES ............................................................................. 
21 
4.1  Study Endpoints 
.......................................................................................................................... 
21 
4.2  Other Study assessments ............................................................................................................ 
21 
5  CLINICAL INVESTIGATION DESIGN ..................................................................................................... 
22 
6  STUDY PROCEDURE GUIDELINES ....................................................................................................... 
22 
6.1 
Screening and Informed Consent .............................................................................................. 
23 
6.2 
Baseline /Pre-Procedure Assessments ...................................................................................... 
23 
6.3 
Baseline/Pre-procedure CARTOFINDER™ (CF) mapping: 
.......................................................... 
24 
6.3.1  Baseline Mapping Sequence .............................................................................................. 
24 
6.4  Analysis of the CARTOFINDER™ Baseline Map 
........................................................................... 
24 
6.4.1  
CARTOFINDER™ Guided Ablation 
....................................................................................... 
25 
6.4.2  
PVI Ablation: ....................................................................................................................... 
25 
7 DATA COLLECTION AND FOLLOW-UP SCHEDULE ............................................................................. 
26 
7.1  Procedural Data Collection ........................................................................................................ 
26 
7.2  Post-Procedure/Discharge ......................................................................................................... 
27 
7.3  7-Day Follow-Up (Clinic Visit or telephone visit) ....................................................................... 
27 
7.4 
3, 6 and -12 Months Follow-Up (Clinic Visit) ............................................................................. 
27 
8  CONCOMITANT THERAPY.................................................................................................................... 
29 
9  HOLTER MONITOR .............................................................................................................................. 
29 
10  
STUDY POPULATION ....................................................................................................................... 
30 

 
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10.1 Subject Identification 
.................................................................................................................. 
30 
10.2 Inclusion Criteria ......................................................................................................................... 
30 
10.3 Exclusion Criteria......................................................................................................................... 
30 
11 
SUBJECT DISPOSITION ..................................................................................................................... 
31 
12 
SUBJECT WITHDRAWAL/EARLY TERMINATION CRITERIA ............................................................... 
32 
13  INFORMED CONSENT ...................................................................................................................... 
33 
14  
ADVERSE EVENTS AND DEVICE DEFICIENCY REPORTING ................................................................ 
33 
14.1 Introduction ................................................................................................................................ 
33 
14.2 Adverse Events ............................................................................................................................ 
34 
14.3 Reportable Serious Adverse Events (SAE) (MEDDEV 2.7/3 Rev3)............................................... 
37 
14.4 Primary Adverse events 
.............................................................................................................. 
38 
14.5 Anticipated Adverse Events 
........................................................................................................ 
42 
15  
STATISTICAL CONSIDERATIONS 
....................................................................................................... 
47 
15.1 Sample Size ................................................................................................................................. 
47 
15.2 Analysis Populations ................................................................................................................... 
47 
15.3 Statistical Methods ..................................................................................................................... 
48 
15.3.1  Safety .................................................................................................................................. 
48 
15.3.2  Effectiveness ....................................................................................................................... 
48 
15.3.3  Investigational Device Performance ................................................................................... 
48 
15.3.4  Procedural Data .................................................................................................................. 
48 
15.4 
Missing Data Handling ................................................................................................................ 
49 
16 
ADMINISTRATIVE PROCEDURES AND RESPONSIBILITIES ................................................................ 
49 
16.1 Research Ethics Board/Institutional Review Board/Ethics Committee ...................................... 
49 
16.2 Monitoring of the Study 
.............................................................................................................. 
49 
16.3 
Management of Protocol Amendments ..................................................................................... 
50 
16.4 Adherence to the Protocol .......................................................................................................... 
50 
16.5 Records and Responsibilities ...................................................................................................... 
50 
16.5.1  Study Early Termination, Suspension of the Study ............................................................. 
50 
16.5.2  Investigator Records ........................................................................................................... 
51 
16.5.3  Investigator Responsibilities ............................................................................................... 
52 
16.5.4  Sponsor Responsibilities ..................................................................................................... 
53 
16.5.5 Document Retention ........................................................................................................... 
53 

 
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16.6 Regulatory and Ethical Obligations ............................................................................................. 
53 
17  
DATA MANAGEMENT ...................................................................................................................... 
54 
17.1 Data Collection 
............................................................................................................................ 
54 
17.2 Device Accountability.................................................................................................................. 
54 
17.3 Device Returns 
............................................................................................................................ 
54 
17.4 Data Reporting ............................................................................................................................ 
55 
17.5 Source Documentation 
............................................................................................................... 
55 
17.6 Data Verification and Review ...................................................................................................... 
56 
17.7 Final Data Analysis ...................................................................................................................... 
56 
17.8 Confidentiality and Protection of Clinical Investigation Data ..................................................... 
56 
17.9 Publication Policy 
........................................................................................................................ 
56 
18 
RISK/BENEFIT ANALYSIS .................................................................................................................. 
57 
18.1 Potential Risks ............................................................................................................................. 
57 
18.2 
Methods to Minimize Risk .......................................................................................................... 
58 
18.3 Potential Benefits ........................................................................................................................ 
58 
19  
REFERENCES 
.................................................................................................................................... 
59 
20  
ATTACHMENTS ................................................................................................................................ 
62 
20.1 Attachment A: Definitions........................................................................................................... 
62 
20.2 Attachment B: NYHA Functional Classification 
........................................................................... 
66 
 
 

 
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1 ABBREVIATIONS 
AAD   
AntiArrhythmic Drug 
 
ACT   
Activated Clotting Time 
AE    
Adverse Event 
AF/Afib  Atrial Fibrillation 
AT 
 Atrial Tachycardia  
BP 
 Blood Pressure  
bpm   
Beats per minute 
BMI   
Body Mass Index 
CE   
Conformité Européen 
CFAE   
Complex Fractionated Atrial 
Electrogram 
CF   
CARTOFINDER™ 
CFGA   
CartoFinder Guided Ablation 
CHF   
Congestive Heart Failure 
CI   
Confidence Interval 
CL   
Cycle Lenght 
CRA   
Clinical 
Research Associate 
CRF   
Case Report Form 
CRO   
Contract Research Organization 
CT scan  Computerized Tomography scan 
EC   
Ethics Committee 
ECG   
ElectroCardioGram 
eCRF   
electronic Case Report Form 
EDC   
Electronic Data Capture 
EEC   
European Economic Community 
EOS   
End-Of-Study 
EP   
ElectroPhysiological Mapping 
ER   
Emergency Room 
EU   
European 
Union 
FAM   
Fast Anatomical Mapping 
FDA   
Food and Drug Administration 
FI   
Focal Impulses 
GCP   
Good Clinical Practice 
GI   
GastroIntestinal 
HCP   
Health Care Provider 
HR   
Hazard Ratio 
ICD   
Implantable Cardioverter- 
Defibrillator 
ICE   
Intra-Cardiac Echography 
ICH   
International Conference 
on 
 
Harmonisation 
IFU   
Instructions for Use 
 
 
IRB/EC  
Institutional Review Board / Ethics 
Committee 
ISO   
International Organization for 
Standardization  
ITT  
Intent-To-Treat 
IV   
IntraVenous 
LA   
Left Atrium 
LAT   
Local Activation Time 
LV   
Left Ventricle 
LVEF   
Left Ventricular Ejection Fraction 
MedDRA®  Medical Dictionary for Regulatory 
Activities 
MI 
 Myocardial Infarction  
MRI   
Magnetic Resonance Imaging 
N   
Number 
NSR 
 Normal 
Sinus Rhythm  
PE   
Physical Examination  
PV   
Pulmonary Vein 
PVI   
Pulmonary Vein Isolation 
QA   
Quality Assurance 
RA   
Right Atrium 
RAP   
Repetitive Activation Patterns 
RF   
RHYTHMFINDER 
RV   
Right Ventricle 
RF   
RadioFrequency 
SAE   
Serious Adverse Event 
SADE   
Serious Adverse Device Effect 
SAP   
Statistical Analyis Plan 
SAS   
Statistical Applications Software 
SOC   
System Organ Class 
SVC   
Superior Vena Cava 
UADE 
 Unanticipated Adverse Device Effect  
UAE 
 Unanticipated Adverse Event 
US   
United States 
VT   
Ventricular Tachycardia

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2  INTRODUCTION 
2.1 Background 
The ability to diagnose complex arrhythmias has enabled technologies such as catheter ablation to 
become more prevalent; however, even with these technologies, 1-year success rate for AF ablation 
off medications is 40% to 60% for 1 procedure [1,2,3] with a “70% ceiling” for 3 or more procedures. 
Multiple studies have demonstrated that success rates of PVI are lower in patients with persistent 
AF[4,5]. 
The possible explanation for the low success rates is that the current tools may not create durable 
lesions as evidenced by pulmonary vein reconnection [6, 7] and gaps in linear lesions [8, 9] in 
patients with recurrent AF after  ablation. Also, the mechanisms that sustain AF are not identified [2, 
10, 11].  Haissaguerre and colleagues found that linear lesions were often arrhythmogenic  due to 
gaps in the ablation lines and that many patients were ultimately cured with ablation of a single 
rapidly firing ectopic focus [12]. 
Map-guided ablation showed to be more effective than conventional ablation alone at preventing 
early and late arrhythmia recurrences [13,14] 
Mapping and catheter ablation of ablation targets including repetitive activation patterns (RAPs) and 
focal impulses (FI) appear to show  advantage to reduce recurrence of atrial arrhythmias versus the 
conventional AF ablation approach. The further  development of mapping techniques and software to 
analyze and as such identify locations that sustain arrhythmia and help guide the ablation procedure 
may increase the long- term outcome for subjects with persistent AFib. 
 
2.2 Clinical Investigation Overview 
The purpose of this trial is to assess safety and effectiveness of using the CARTOFINDER™ (CF) maps 
created by the RHYTHMFINDER (RF) basket catheter 
 
 and the CARTOFINDER™ System using the 4D LAT algorithm in treating persistent atrial 
fibrillation (PsAF). The CARTOFINDER™ 4D LAT Algorithm provides automatic analysis of multiple 
simultaneous ECG signals when recorded by a multi-electrode catheter by generating a 
CARTOFINDER™ Map that helps to facilitate the identification of ablation targets including Repetitive 
Activation Patterns (RAPs) or Focal Impulses (FI) or other ablation targets. 
 
 

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2.3 Device Description 
Table 2.3 below outlines the required devices for the study and their current regulatory status. 
 
Table 2.3 Cross-Jurisdictional Regulatory Status of Study Devices 
Devices 
Europe  
Canada 
CARTOFINDER™ Workstation, with 4D LAT Algorithm 
installed 
CE Marked  
Investigational 
CARTO® 3 EP Navigation System, with CARTOFINDER™  
installed (CARTOFINDER™ Module) 
CE Marked  
Investigational 
RHYTHMFINDER Basket Catheter 
Investigational Investigational 
 
The CE marked devices are compliant with Medical Device Directive 93/42/EEC and the relevant 
harmonized standards as well as conform to the applicable local regulations and are to be used 
according to the approved indication and their instructions for Use (IFU). 
 
2.3.1 CARTOFINDER™ Workstation with 4D LAT Algorithm 
The CARTOFINDER™ Workstation is a computerized system that assists in the diagnosis of complex 
cardiac arrhythmias and displays the arrhythmias in a dynamic visual format. 
The  CARTOFINDER™ Workstation takes recorded electrical signals collected from multi-electrode 
catheters as inputs.  It then generates output data that is displayed as static or dynamic 4D maps 
which can assist in the diagnosis of cardiac arrhythmias. 
Specifically, the CARTOFINDER™ accesses stored data of recorded electrical heart activity obtained via 
conventional electrophysiological methods using multi-electrode catheters placed in the heart.  
Using the 4D LAT software algorithm, these recorded signals  are  analyzed  by the CARTOFINDER 
and presented as 4D maps of the activation patterns of various heart rhythms that include normal 
sinus rhythm (NSR), atrial flutter (AFL) and atrial fibrillation (AF).  The 4D maps are graphically 
displayed on  a monitor screen for review  by the investigator during an electrophysiology study. 
 
2.3.2 CARTO® 3 EP Navigation System with CARTOFINDER™ Module 
The CARTO® 3 EP Navigation System with CARTOFINDER™ Module is a catheter- based atrial and 
ventricular mapping system designed  to acquire and analyze data points, and use this information to 
display 3D anatomical and electroanatomical maps of the human heart in real-time. The location 
information needed to create the cardiac maps and the local electrograms are acquired using 
specialized mapping catheters and location reference devices. The system allows real-time display of 
electrograms and cardiac  maps in a number of different  formats  based on the intra- cardiac  
signals received from the catheters. For example, maps may be displayed as anatomical maps, cardiac  

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electrical  activation maps, cardiac electrical propagation maps, cardiac electrical potential maps, 
impedance maps, cardiac chamber geometry, and ECG fragmentation maps. The acquired patient 
signals, including body surface ECG and intracardiac electrograms (ICECG) may also be displayed on the 
display screen.  
The CARTO® 3 EP Navigation System with CARTOFINDER™ Module maintains the identical intended 
use, fundamental scientific technology, software, magnetic location mapping technology, and location 
sensor accuracy as that of the currently cleared CARTO® 3 EP Navigation System.  
The addition of the CARTOFINDER™ Module to the currently cleared CARTO® 3 EP Navigation System, 
enables the CARTO® 3 EP System to interface with a newly developed cardiac mapping system called 
the CARTOFINDER™ Workstation.  This interface displays the CF maps computed by the 
CARTOFINDER™ Module. 
2.3.3 RHYTHMFINDER™ 192 Catheter (
) 
The Biosense Webster RHYTHMFINDER™ 192 Catheter is a multi-electrode mapping catheter.  This 
basket-style catheter is designed to provide a global view of the cardiac surface with electrical 
activation information and is meant for atrial mapping only.  
 
 
  
The RF-192 mapping catheter 
 
 is intended to be deployed in the atria through a commercially available sheath utilizing 
the CARTO® 3 EP Navigation System. This catheter is not compatible with CARTO
® 3 EP Navigation 
Systems prior to Version 5. The catheter is “basket-like” in design and can be used for recording of 
intracardiac signals during the EP procedure. The design is intended to maximize contact and coverage 
within the chambers of the right and left atrium. 
 
 
 
 
2.3.4 Ablation catheters 
The THERMOCOOL® SMARTTOUCH™ and THERMOCOOL® SMARTTOUCH® SF Diagnostic /Ablation 
Deflectable Tip Catheters with Contact Force Sensing Capability, are the only study catheters to be used 
in this study within their country specific commercial availability and indications for use. It’s 
recommended that for this study the investigator uses the same catheter type, THERMOCOOL® 
SMARTTOUCH™ or THERMOCOOL® SMARTTOUCH® SF, throughout the study conduct for all his/her 
patients. 
A copy of the IFU for the Study Catheters and interface cable is included in each product package. 

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3 CLINICAL INVESTIGATION OBJECTIVES 
The primary purpose of this trial is to assess safety and effectiveness of using the CARTOFINDER™ (CF) 
maps created by the RHYTHMFINDER (RF) basket catheter 
 
 and the CARTOFINDER™ System using the 4D LAT algorithm in treating persistent atrial 
fibrillation (PsAF).. The CARTOFINDER™ 4D LAT Algorithm provides automatic analysis of multiple 
simultaneous ECG signals when recorded by a multi-electrode catheter by generating a 
CARTOFINDER™ Map that helps to facilitate the identification of ablation targets  including Repetitive 
Activation Patterns (RAPs) or Focal Impulses (FI) or other ablation targets enables one to evaluate the 
effects of treatment. In addition, the study will also assess, procedural data, mapping data and 
mapping catheter functionality. 
 
4 CLINICAL INVESTIGATION OUTCOME MEASURES 
4.1 Study Endpoints 
Effectiveness 
 Acute success defined as: Rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm or 
Atrial Tachycardia, after CFGA and PVI (without cardioversion) 
 Procedural success defined as: Conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial 
Tachycardia after overall ablation procedure, with or without the need for cardioversion 
 Rate of conversion of Atrial Fibrillation to Normal Sinus Rhythm or Atrial Tachycardia, after 
CFGA only (before PVI and without cardioversion) 
 Freedom from documented symptomatic AF/AT/AFL recurrence (episodes ≥ 30 seconds on an 
arrhythmia monitoring device) post the 3-month blanking period through the 12-month follow 
up. 
 Incidence of PVI (confirmed entrance block) after adenosine/isoproterenol challenge 
 Change of intra-cycle length from pre-CFGA to post-CFGA and post-PVI  
 
Safety 
 Incidence of early-onset Primary Adverse Events (refer to section 14 for a list of events). 
 Incidence of study device and procedural related SAEs during follow-up period (12M) 
 Incidence of all SAEs during follow-up period (12M) 
 Incidence of study device and procedure related adverse events 
 
4.2 Other Study assessments 
 Number of identified CF ablation targets  
 Max #of active RF 192 electrodes during initial mapping procedure 
 AAD use post the 3-month blanking period  
 Incidence of repeat ablation procedures for AF post the 3-month blanking period 

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 Procedural data: 
o All target sites for RF lesion application 
 Location of ablation targets 
 Number of RF applications per target 
 Total RF duration per application 
o RF ablation parameters (including but not limited to: power, contact force, impedance, 
flow rate, temperature)  
o Total fluoroscopy time time anddose 
o Total procedure, mapping and ablation time 
 
5 CLINICAL INVESTIGATION DESIGN 
The study is a prospective, single arm, non randomized, open label, multicenter study. 
Subjects fulfilling the inclusion / exclusion criteria and who sign the informed consent form (ICF) will be 
enrolled in the RAPID-AF study. The clinical investigation is targeting approximately 6-10 centers located 
worldwide. The study will enroll approximately 40 to 70subjects.  
This study will serve to generate a clearer perspective of the CARTOFINDER™ System’s ability to 
generate maps for guiding ablation and the investigator’s ability to maneuver, acquire signals etc. using 
the RF-192 catheter. 
Subjects displaying an ablation target on the CARTOFINDER™ (CF) map will undergo CARTOFINDER™ 
Guided Ablation (CFGA) followed by PVI (WACA) ablation. Subjects not displaying an ablation target on 
CARTOFINDER™  will be will be treated per investigator’s standard of care and followed up until 7 days 
post-procedure.  
 
6 STUDY PROCEDURE GUIDELINES 
The devices itemized below are required for this protocol, and investigational devices will be provided 
by the sponsor. Refer to the Table 2.3 for the status of the devices in your region. 
 CARTO® 3 EP Navigation System, with CARTOFINDER™ Module 
 CARTOFINDER™ Workstation 
 RHYTHMFINDER Basket Catheter (Mapping Catheter) 
Ablation catheters used for this study protocol are THERMOCOOL® SMARTTOUCH™ or SMARTTOUCH® 
SF Catheter (Ablation Catheter) (commercially available and used within indication for use as 
applicable for your country). 
Biosense Webster representatives will provide training to the study site personnel in the use of the 
investigational devices. 
Refer to the Instructions for Use for the set-up of the devices and respective connections. 
 

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6.1 Screening and Informed Consent 
Subjects presenting to the institution with Persistent Atrial Fibrillation and considered for an ablation 
procedure should be screened by the investigator or designated member of the research team for 
study eligibility per the protocol inclusion and exclusion criteria. 
The study investigator or designated member of the research team will obtain written informed 
consent from the subject. The background of the proposed study and the potential benefits and risks of 
the study should be explained to the subject.  The subject or legal representative must sign the 
consent form prior to any study-specific exams or tests are provided to them that fall outside of 
the standard  of care. The consent form used must have prior approval from the study site's Research 
Ethics Board/ Institutional  Review  Board / Ethics Committee.  Failure to obtain informed consent 
renders the subject will be deemed ineligible for participation in the study. 
Each subject screened for enrollment in the clinical investigation who signs the patient informed 
consent form will be enrolled into the study. 
6.2 Baseline /Pre-Procedure Assessments 
Pre-procedure assessments and data collection must be performed within 30 days prior to the ablation 
procedure unless otherwise noted. 
- Demographics 
- Medical history 
- Arrhythmia history 
- Cardiovascular medication including anticoagulation regimen 
- Electrocardiogram (12-Lead ECG) 
- INR (prior to ablation procedure), when applicable 
- CHADS-VASC2 Score 
- NYHA assessment 
- Imaging (i.e. 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) 
- If left atrial size exceeds 47 mm on TTE, left atrial volume should be measured. 
 Imaging for detection of LA thrombus is mandatory within 24 hours prior to ablation 
procedure. The imaging method used is at the discretion of the investigator and institution 
standard practices: 
- Transesophageal Echocardiogram (TEE) 
- Intracardiac Echocardiography (ICE) 
- Computed Tomography (CT) 
- Magnetic Resonance Imaging (MRI) 
 Pregnancy test must be done on pre-menopausal women only, within 1-week of the procedure 
and documented in the subject’s medical chart. 
Subjects who signed the informed consent form and who meet all inclusion and no exclusion criteria 

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at screening/baseline will undergo a CARTOFINDER™ (CF) baseline map using the RHYTHMFINDER™ 
192 Catheter 
 
6.3 Baseline/Pre-procedure CARTOFINDER™ (CF) mapping: 
Subjects will arrive to the electrophysiology laboratory for their clinically indicated ablation 
procedure and will undergo preparation for the ablation procedure according to the hospital’s 
standard protocol (discretion of investigator), CARTO3 navigational and electro-anatomical mapping 
system.  CARTOFINDER™ System is connected to CARTO®3 workstation with Ethernet cable for file 
sharing as per Instruction For Use (IFU). 
6.3.1 Baseline Mapping Sequence 
All eligible subjects will undergo the CARTOFINDER™ Mapping Procedure, using the RF-192 catheter. 
The subject must be in AF prior to the insertion of the RF-192 Mapping catheter. If the subject is 
not in AF at the time of the procedure the patient will be regarded as discontinued per inclusion 
criteria, followed for 7-days post-procedure and exited from the study. 
 Standard Fast Anatomic Mapping (FAM) procedure of the Right Atria (RA) using the 
THERMOCOOL SMARTTOUCH™ or SMARTTOUCH® SF Catheter. 
 Baseline CARTOFINDER™ map, recording of the RA using the RF-192 catheter 
- On deployment of the RF-192 catheter, the  basket  catheter will be placed in optimal 
position to maximize contact with the RA wall 
- Once the catheter’s position is confirmed and contact is optimal, the investigator 
will obtain intra-cardiac signals 
- One 30 second recording will be obtained 
DO NOT perform any RA ablations at this point 
 Transseptal Puncture 
 Standard FAM of the Left Atria (LA) using the THERMOCOOL® SMARTTOUCH™ or 
SMARTTOUCH® SF Catheter. 
 Baseline CARTOFINDER™ map, recording of the LA using the RF-192 catheter 
- On deployment of the RF-192 catheter, the basket catheter will be placed in optimal 
position to maximize contact with the LA wall 
- Once the catheter’s position is confirmed and contact is optimal, the 
investigatorinvestigator will obtain intra-cardiac signals 
- One 30 second recording will be obtained 
RF192 catheter must not remain in the subject (being deployed in the atrium) for cumulative 
duration greater than 1.5 hours (90 mins)  
 
6.4 Analysis of the CARTOFINDER™ Baseline Map 
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processed and analyzed for the presences of ablation targets including FI/RAPs by the treating/ablating 
investigatorwho has been trained by Biosense Webster personnel knowledgeable in analyzing CF 
maps and the operation of the CARTOFINDER™ system. 
Ablation Targets (FI/RAP) identification: 
 Identify areas with ablation targets including focal impulse (FI) or repetitive activation patterns 
(RAPs) 
- If an ablation target is identified, the subject will receive CFGA followed by PVI  
- If no CF ablation target is identified, the subject will be treated per standard of care and 
exits the study after 7 day follow up. 
No RF ablation should occur prior to analysis of the CARTOFINDER™ Maps. 
 
6.4.1 CARTOFINDER™ Guided Ablation 
All subjects will undergo CARTOFINDER™ Guided Ablation procedure followed by PVI. 
 Confirm identified ablation targets on the Baseline CF map 
 Ablate areas using the THERMOCOOL® SMARTTOUCH™ or SMARTTOUCH® SF Catheter identified by 
the CARTOFINDER™  map 
- If a post CFGA map is performed on the ablated atrium(a), analysis of the post-CFGA CF map 
for the existence of ablation targets should be performed 
 Complete above steps until one of the following conditions is met: 
- No further ablation targets are identified on the CF Map 
- Subject achieves normal sinus rhythm or an atrial tachycardia 
The final decision to not further ablate remaining RAP/FIs regardless of above criteria being 
met or not, remains at investigator’s discretion. 
 After performing any CFGA, a CF map may be created at the investigator’s discretion, but is not 
required.  
 If subject is in AF (or other arrhythmia) after CFGA, no cardioversion is permitted.  
 
RF192 catheter must not remain in the subject (being deployed in the atrium) for cumulative duration 
greater than 1.5 hours (90 mins)  
 
6.4.2 PVI Ablation: 
All subjects enrolled in the study will undergo the following PVI procedure as outlined below.   
1. Pulmonary Vein Isolation will be performed using Wide Area Circumferential Ablation (WACA) 

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technique per the institution’s standard practice. 
2.   Confirmation of complete entrance block must be performed after the WACA 
 If NSR is achieved through PVI, no further ablations are permitted other than to complete the 
PVI. 
 If AT is achieved, additional ablations are permitted to ablate the Atrial Tachycardia at the 
investigator’s discretion. 
 If AFL is achieved, the placement of additional RF lesions (i.e. Linear lesions at the cavotricuspid 
isthmus) is at the discretion of the investigator  
 
Prophylactic ablation of empirical sites is not allowed per protocol. 
All linear lesions, if any, require confirmation of conduction block by pacing and/or mapping 
maneuvers 
3.   Perform a final CF Map* within the same atrium (a) in which the baseline map was collected. 
*AT: once achieved, one “post” ablation CF map is required 
*NSR: a “post” ablation CF map is at the discretion of the investigator 
4.   If subject in AF/AFL/AT after completing ablations, cardioversion may be performed at the 
discretion of the investigator ONLY after completing all ablations. 
 
7 DATA COLLECTION AND FOLLOW-UP SCHEDULE 
7.1 Procedural Data Collection 
The following procedural data will be collected: 
 Mapping sequence 
 Procedural flow 
 Procedural time including RF ablation and mapping times 
 Fluoroscopy usage 
 Ablation targets and parameters  
o Areas/location of ablation targets including RAPs/Focal impulses identified by 
CARTOFINDER™  
o # RF applications per target 
o RF duration per application 
 Cycle length 
 Max #of active RF 192 electrodes  
 Fluid inputs/outputs 
 Subject’s heart rhythm (pre-and post-ablations)  
 Rate controlling medications provided inter-operatively 
 Intra-Procedural complications. 

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 All CARTOFINDER™ maps with associated catheter locations 
 Investigator feedback on quality of signal collection and mapping at the end of the procedure.  
The survey will contain questions to rate on a scale of 1 to 5 and will be entered into the eCRF 
for analysis. 
7.2 Post-Procedure/Discharge 
Once the investigator has achieved the desired results for the subject’s arrhythmia, the subject will be 
monitored as per the institution standard of care (post procedure practice) and subject will be 
discharged from the hospital in accordance with the hospitals standard procedures. 
The following data will be collected at Discharge: 
 Arrhythmia assessment 
 Adverse Events Procedural complication collection and notification 
 Electrocardiogram (12-Lead ECG andcycle length in diagnosed rhythm) 
 Cardiovascular medication and anti-coagulation therapy. 
7.3 7-Day Follow-Up (Clinic Visit or telephone visit) 
All subjects will be contacted 7-days post procedure via telephone or by attending a clinic visit. 
The following data will be collected for all subjects at 7 days post- procedure: 
 Arrhythmia assessment 
 Medical/hospitalization assessment 
 Concomitant cardio-vascular medication and anti-coagulation therapy 
 Adverse event assessment and notification 
7.4 3, 6 and -12 Months Follow-Up (Clinic Visit) 
The following data will be collected for all subjects: 
 Medical / Hospitalization assessment 
 Arrhythmia assessment  
 Electrocardiogram (12-Lead ECG and cycle length in diagnosed rhythm) 
 Arrhythmia Monitoring: 
- 24-hour Holter at 3 month visits 
- ≥72 hours Holter at 6 and 12 months 
 Concomitant cardiovascular medication and anti-coagulation therapy: subjects are 
recommended to stop their AAD medication after 3- months at the discretion of the 
investigator 
 Adverse event assessment and notification 
Repeat ablations may be performed at the discretion of the investigator. Investigators are 
recommended to treat the subject using the same commercial available ablation catheter 
(THERMOCOOL® SMARTTOUCH™ Catheter and/or SMARTTOUCH® SF Catheter) as the initial procedure. 
The follow-up schedule will remain based on the initial procedure. 

 
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                              Table 7.4 Time and Follow-up Schedule 
 
 
Screening 
/ 
Baseline 
Ablation 
Procedure1 Discharge 
7 Days 
+/- 2 day 
3 Month 
+/- 1 wks. 
6 Month 
+/- 
2 wks. 
12 Month 
+/- 4 wks. 
Informed 
consent1 
X 
  
  
 
  
  
 
Inclusion 
& exclusion 
criteria 
X 
  
  
 
  
  
 
Demographics 
X 
  
  
 
  
  
 
Medical assessment 
X [history]   
 
X 
X 
X 
X 
Arrhythmias 
X [history]  
X 
X 
X 
X 
X 
ECG (12 lead andCL 
measurement) 
X 
 
X 
 
X 
X 
X 
NYHA/CHADS-VASC2 
score 
X 
  
  
 
  
  
 
Pregnancy 
Test2 
X 
  
  
 
  
  
 
Assessment LA 
Thrombus3  
X 
  
 
  
  
 
TTE4 
X 
  
  
 
  
  
 
Ablation assessments 
 
X 
  
 
  
  
 
Arrhythmia 
Monitoring 
(Holter) 
8 
 
  
  
 
X 
X 
X 
Device 
Deficiency 
 
X 
  
 
  
  
 
Concomitant 
Medications5 
X 
X 
X 
X 
X 
X 
X 
Adverse 
events6 
X 
X 
X 
X 
X 
X 
X 
1 Informed Consent to be obtained and collected prior to any study specific 
assessments 
2 Pregnancy test must be done on pre-menopausal women only within 
1 week 
prior to procedure. 
3 Imaging method as per standard hospital practice 
(TEE, ICE,…); within 24 hours 
prior to procedure 
4 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). 
If LA 
diameter is ≥47mm, LA volume to be measured. 
 
5 
Concomitant medications: only cardiac related (AAD drugs, 
anticoagulation regimen, etc.). 
6  AEs will be collected once consent has been 
signed 
7  End of study (CRF) page to be completed 
for ALL enrolled subjects 
8  Holter: Dispensation of Holter device at Month 3 visit. 
24-hour Holter 
monitoring at 3 month and ≥72-hour Holter monitoring 
at 6 and 12 months 
follow-up. 
 
 

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8 CONCOMITANT THERAPY 
The following medications may be administered (as indicated and per standard of care and per the IFU) 
for subjects undergoing catheter ablation. 
 
Before Ablation: 
- Anticoagulation: therapy is recommended for 30 days before the ablation procedure. 
- Anti-Arrhythmic Drug (AAD): subjects AAD therapy should be managed per the 
institutions/investigator’s standard of care.  
An intravenous bolus of Heparin should be administrated before 
introducing RF-192. 
 
Mapping Procedure: While the RF-192 catheter is in the subject’s right atrium, the ACT must be 
maintained at > 300; while placed in the left atrium, the ACT must be maintained 
at > 350.  When the RF-
192 catheter is not in the subject’s atrium e.g. in between mapping procedures, the ACTs may be 
reduced, but must remain at > 300 while the catheter 
is inside the subject. 
 
Ablation Procedure: Maintain an ACT greater than 300 seconds for right- sided procedures and above 
350 seconds for left-sided procedures as in accordance with the current ACC/AHA/ESE guidelines.  Post 
ablation pacing procedure(s) and/or infusion of cardiac medications to induce AF are at the discretion of 
the investigator (e.g., Isoproterenol 2 to 20 mcg/min). 
 
Following Ablation: 
- Anticoagulation therapy is strongly recommended for 3 months following ablation. 
Thereafter, subjects are recommended to receive anti-coagulation therapy in accordance 
with the ACC/AHA/HRS 2014 Guidelines for the Management of Patients in Atrial Fibrillation 
[2, 15] 
- At the discretion of the investigator, a previously ineffective drug, at the same dose or 
lower, may be continued during the 3-month blanking period. Subsequent use of anti-
arrhythmic drugs is discouraged   
- Additional medications needed to treat clinical indications 
are at the discretion of the clinical 
investigation 
investigator 
 
9 HOLTER MONITOR 
All subjects will be provided with a Holter monitor device at pre-specified scheduled visits (refer 
to Table 7.4) to capture recordings of their heart rhythm status and will be asked to report on any 
symptoms they experience. The recordings from the Holter monitor will be transmitted to a Core Lab 
for analysis. Subjects will be trained by the study site personnel on the use of the Holter monitor 
device and transmission of the recordings. A study specific Core Lab instruction manual and patient 

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instruction sheet, including procedures to be followed, will be made available. 
Holter monitoring will be conducted 
as follows: 
o 3-Month Visit: 24-hour Holter Monitor 
o 6 and 12 Month Visits: >72 hours Holter Monitor 
 
 
 
10 STUDY POPULATION 
10.1 Subject Identification 
Subjects will be identified sequentially at each site by number only. The subjects will be identified by 
site number and subject number. 
All information and data sent to the sponsor concerning subjects or their participation in this clinical 
investigation will be considered confidential and transmitted anonymously. Only authorized sponsor 
personnel or designee, or local government authorities acting in their official capacities will have 
access to these confidential files. All data used in the analysis and reporting of this evaluation will be 
without identifiable reference to the subject. 
The following inclusion and exclusion criteria were selected to ensure the appropriate study 
population is enrolled. 
10.2 Inclusion Criteria 
1. Age > 18 years. 
2. Patients who have signed the Patient Informed Consent Form (ICF) 
3. Scheduled to undergo a clinically-indicated catheter ablation procedure for treatment 
of 
a. persistent atrial fibrillation (defined as continuous atrial fibrillation that is sustained 
beyond seven consecutive days). 
b. drug-resistant atrial fibrillation. (failed 1 or more class I or III antiarrhythmic drugs) 
and demonstrating Persistent AF (requiring drugs or electrical shock to terminate 
4. In AF at the time of the baseline CARTOFINDER™ Map (spontaneous) 
5. Left Atrium (LA) must demonstrate sufficient electrical activity to allow for the identification of 
ablation targets. 
6. Able and willing to comply with all pre-, post-, and follow-up testing and requirements (e.g. 
patients not confined by a court ruling) 
10.3 Exclusion Criteria 
1. Paroxysmal Atrial Fibrillation 
2. Continuous AF > 12 months (1-Year) (Longstanding Persistent AF) 
Subjects previously diagnosed as Long Standing Persistent (LSP) but have demonstrated the 

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ability to maintain Normal Sinus Rhythm for >30 days after cardioversion and have not been 
in AF greater than 1 year at the time of the procedure remain eligible for inclusion.  
3. Previous ablation procedure for PsAF (defined as ablations involving more than only PV isolation) 
4. Patients with a left atrial size >55 mm (echocardiography, parasternal 
long axis view). 
5. Inability to restore sinus rhythm for 30 seconds or longer in the opinion of the investigator. 
6. Significant congenital anomaly or medical problem that in the opinion of the investigator would 
preclude enrollment in this study. 
7. Atrial arrhythmia patients with structural atrial disease such as a prior history of atriotomy from 
prior atrial surgery, presence of an atrial septal defect, and/or presence of an atrial septal closure 
patch. 
8. History of or current blood clotting or bleeding abnormalities, contraindication to systemic 
anticoagulation (i.e., heparin, warfarin, dabigatran, or a direct thrombin inhibitor). 
9. Significant pulmonary disease, cardiac surgeries, unstable angina, uncontrolled heart failure, 
acute illness or systemic infection, or any other disease or malfunction that would preclude 
treatment in the opinion of the investigator. 
10. 
Current enrollment in a study evaluating another device or drug. 
11. 
A complex arrhythmia secondary to electrolyte imbalance, thyroid disease, or reversible or 
non-cardiac cause. 
12. 
Any cardiac surgery within the past 60 days (2 months) (includes PCI) 
13. 
Subjects that have ever undergone valvular cardiac surgical procedure (i.e., ventriculotomy, 
atriotomy, and valve repair or replacement and presence of a prosthetic valve) 
14. 
Prior ICD or pacemaker 
implanted 
15. 
Presence of intramural thrombus, tumor or other abnormality that precludes catheter 
introduction 
or manipulation. 
16. 
Presence of a condition that precludes vascular access. 
17. 
Subject has a contra-indication to the device under study per the IFU 
18. 
Women of child bearing potential that are pregnant, lactating, or planning to become pregnant 
during the course of the trial. 
 
 
11 SUBJECT DISPOSITION 
The following subject groups are defined: 
 Enrolled Subjects: Subjects who have signed and dated the Informed Consent Form. 
 Excluded Subjects: Enrolled subjects who have signed an ICF but are found not meeting 
eligibility criteria prior to insertion of the RHYTHMFINDER™ 192 Catheter.  
 Mapping Failure:  Enrolled subjects who have the RHYTHMFINDER™ 192 Catheter inserted and 
where inability to record baseline CF mapping signals is observed, will be followed up for 7-days. 

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If an SAE is reported for a mapping failure subject, they will be followed until event resolution or 
stabilized. The investigator will document mapping failures in the electronic 
CRF, including reasons 
for failure. 
 Discontinued Subjects:  Enrolled subjects who have the RHYTHMFINDER™ 192 Catheter inserted 
but do not undergo CF guided ablation. If subject’s arrhythmia is determined at the time of EP 
study to be a non-study arrhythmia (required for subject enrollment per study inclusion criteria), 
the subject will be categorized as discontinued subject. Discontinued subjects will remain in 
follow-up for 7-days. If an SAE is reported for a discontinued subject, they will be followed until 
event resolution or stabilized. 
 Lost to Follow-up Subjects: Subjects who are enrolled and have the RHYTHMFINDER™ 192 
Catheter inserted, but contact is lost after most recent follow-up visit (despite 3 documented 
attempts 
to contact the subject). 
 Withdrawn / Early Termination Subjects: Subjects who have RHYTHMFINDER™ 192 Catheter 
inserted but 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 complete the last scheduled follow-up visit per study 
protocol. 
12 SUBJECT WITHDRAWAL/EARLY TERMINATION CRITERIA 
Every subject should be encouraged to remain in the study until they have completed the protocol-
required 1 year follow-up period. If the subject terminates prematurely from the study, the reason 
for early termination must be documented by the investigator in the source documents and in the 
appropriate electronic CRF section. 
Possible reasons for early termination may include 
but are not limited to the following: 
 Withdrawal of consent: Subject may withdraw from the clinical investigation at any time. 
The decision must be an ‘independent decision’ that is documented in the source 
documentation and in the electronic CRF. 
 Investigator discretion: the investigator may choose to withdraw a subject from the study if 
there are safety concerns. 
 Death 
 Study Termination – The sponsor can decide to discontinue the study prematurely for various 
reasons. 
 Lost to follow-up – All subjects should be encouraged to return for protocol required office, 
clinic visit 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 to the subject. 

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If the subject does not respond to the letter, then the subject will be considered “lost to 
follow-up” for the current study visit.  Subject contact must be attempted at each follow-up 
time point and if unable to contact the subject after 3 phone calls, the subject should 
once again be sent a certified letter.  Only after failing to contact the subject at the final 
follow-up visit will the subject be considered lost to follow-up and the study termination/end 
form will be completed in the individual case report 
form. 
13 INFORMED CONSENT 
Prior to screening or performing any study related procedures that are solely for the purpose of 
determining eligibility for this study, any potential benefit and risk of the study must be 
explained to the subject directly 
Subjects will be informed about all aspects of the study that are relevant to the subject's 
decision to participate throughout the study and requested to grant their approval to 
review their medical records, to collect and analyze personal medical information, while 
maintaining confidentiality of the records at all times. 
Subjects will also be asked to agree to comply with the follow up visits during the 1-year follow 
up period.  The informed consent needs to be written in a native non-technical language 
that is understandable to the subject and needs to be approved by Research Ethics Board / 
Institutional Review Board / Ethics Committee.  The subject will be provided ample time to 
read and understand the informed consent form and to consider participation in the study. The 
informed consent will be requested prior to screening and must be personally signed and dated 
by the subject directly prior to performance of any study related activity or procedure. If a 
subject is unable to read or write, informed consent shall be obtained through a supervised 
oral process. An independent witness (as applicable) shall be present throughout the process. 
The written informed consent form and any other information shall be read aloud and 
explained to the prospective subject and, whenever possible, subject shall sign and personally 
date the informed consent form. The witness also signs and personally dates the informed 
consent form attesting that the information was accurately explained and that informed 
consent was freely given. The point of enrollment corresponds with the time that subjects signs 
the informed consent. 
The Informed consent should be obtained by the investigator who is a licensed doctor when 
necessary as per the local regulation. 
14 ADVERSE EVENTS AND DEVICE DEFICIENCY REPORTING 
14.1 Introduction 
Below sections are mainly applicable for EU requirements and definitions, AE classifications, 
reporting and compliance sections might differ per local regulations for other regions. 
Event reporting to relevant competent authorities in accordance with the jurisdictional 

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regulations will occur by the sponsor and/or by the investigator, depending upon the local 
requirements and will be done in EU per MEDDEV 2.12/1 guidelines for CE-marked devices 
manufactured by Biosense Webster and per MEDDEV 2.7/3 guidelines for non CE-marked 
devices manufactured by Biosense Webster. 
 
14.2 Adverse Events  
An Adverse Event is any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device. This definition includes 
events related to the investigational medical device and to the procedures involved.  
For users or other persons, this definition is restricted to events related to investigational 
medical devices. 
As from point of enrollment, at each evaluation and whenever the investigator becomes aware 
of an event, the investigator determines for each enrolled subject whether any adverse events 
(AE) have occurred, and determines their relationship to the investigational medical device and 
procedure as well as the seriousness of the event. 
All adverse events must be recorded in the electronic CRF(s) in a timely manner throughout the 
clinical investigation and shall be reported to the sponsor together with an assessment without 
unjustified delay. 
The date of the adverse event, treatment, resolution, assessment of both seriousness and 
relationship to the investigational device should be provided if available. 
Subjects should be encouraged to report AEs spontaneously or in response to general, non-
directed questioning (e.g., “How has your health been since the last visit?”). Any time during the 
clinical investigation, the subject may volunteer information that resembles an AE. If it is 
determined that an AE has occurred, the investigator should obtain all the information required 
to complete the AE Form of the electronic CRF. 
All AEs must be followed until resolution or until a stable clinical endpoint is reached. The safety 
officer or designee of this clinical investigation will decide if more follow up information is 
needed in case the event is not resolved or stable at study completion. All required treatments 
and outcomes of the adverse event must be recorded in the electronic CRF(s). 

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The Sponsor is responsible for the classification of adverse events and ongoing safety evaluation 
of the clinical investigation and shall review the investigator’s assessment of all adverse events. 
The Sponsor will determine and document in writing their seriousness and relationship to the 
investigational device. In case of disagreement between the Sponsor and the principal 
investigator(s), the sponsor shall communicate both opinions to the concerned parties,  
The following categories of adverse event severity are to be used: 
 
Mild 
Any event resulting in minimal transient impairment of a body function or 
damage to a body structure, and/or does not require intervention other 
than monitoring. 
Moderate 
Any event resulting in moderate transient impairment of a body function or 
damage to a body structure, or which requires intervention, such as the 
administration of medication, to prevent permanent impairment of a body 
function or damage to a body structure 
Severe 
Any life threatening event, resulting in permanent impairment of a body 
function or damage to a body structure, or requiring significant 
intervention, such as major surgery, to prevent permanent impairment of a 
body function or damage to a body structure. 
The causal relationship to the investigational medical devices and procedure should be rated as 
follows, please refer to MEDDEV 2.7/3 Rev3 for detailed definitions: 
Definitely Device-related The event is associated with the investigational device beyond 
reasonable doubt as described per MEDDEV 2.7/3 Rev3. 
Probable Device- related 
The relationship with the use of the investigational device seems 
relevant and/or the event cannot reasonably explained by another 
cause, but additional information may be obtained. 
Possibly Device-related 
The relationship with the use of the investigational device is weak but 
cannot be ruled out completely. 

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Unlikely Device-related 
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 Device-related 
Relationship to the investigational device can be excluded as described 
per MEDDEV 2.7/3 Rev3. 
Definitely Study 
Procedure-related 
The event is associated with the study procedure beyond reasonable 
doubt as described per MEDDEV 2.7/3 Rev3.  
Probable Study 
Procedure-related 
The relationship with the study procedure seems relevant and/or the 
event cannot reasonably explained by another cause, but additional 
information may be obtained. 
Possibly Study Procedure-
related 
The relationship with the study procedure is weak but cannot be ruled 
out completely.  
Unlikely Study Procedure- 
related 
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 Study Procedure-
related 
Relationship to the procedure can be excluded as described per 
MEDDEV 2.7/3 Rev3. 
Outcomes should be assessed as follows: 
Resolved 
Without sequelae - Subject fully recovered with no observable 
residual effects. 
With sequelae - Subject recovered with observable residual effects 
Ongoing 
Improved: Subject’s condition improved, but residual effects 
remain. 
Unchanged: AE is ongoing without changes to the overall condition 
Worsened: Subject’s overall condition worsened. 
Death 
Subject died as a result of the AE (whether or not the AE is related 
to the device or procedure). 
 

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14.3 Reportable Serious Adverse Events (SAE) (MEDDEV 2.7/3 Rev3) 
1.  
Adverse event that: 
a) led to a death   
 
b) led to a serious deterioration in health of the subject, that either resulted in: 
- a life-threatening illness or injury, or 
- a permanent impairment of a body structure or a body function, or 
- in-patient hospitalization or prolongation of existing hospitalization, or 
- in medical or surgical intervention to prevent life threatening illness or 
- injury or permanent impairment to a body structure or a body function. 
c) led to foetal distress, foetal death or a congenital abnormality or birth defect. 
NOTE 1: Planned hospitalization for pre-existing condition, or a procedure required by the Clinical 
Investigation Plan, without a serious deterioration in health, is not considered a serious adverse event. 
 
2.  
 Any Device Deficiency that might have led to a SAE if: 
a) suitable action had not been taken or 
b) intervention had not been made or 
c) if circumstances had been less fortunate 
new findings/updates in relation to already reported events. 
 
The following clinical events are not considered adverse events for this clinical study: 
- Study Arrhythmia recurrence, independently of action taken, by itself is considered a 
recurrence of disease (pre-existing condition), and, therefore, does not meet the definition of 
an AE.   
- AF/AFL/AT occurrence requiring pharmacological or synchronized electrical cardioversion 
during the hospitalization for the index ablation procedure 
- Re-ablation for pre-existing condition itself is not an Adverse Event but any procedural 
complication is considered an Adverse Event and shall be reported within the applicable 
timelines 
 
The investigator must submit to the sponsor (or designee) any SAEs and device deficiencies that could 
have led to a SADE occurring during the clinical investigation immediately but no later than 3 calendar 
days after being notified of the event and provides additional information, if required by the sponsor. 
The investigator will ensure an appropriate follow-up with the enrolled subjects in order to become 
aware of any serious adverse events in an acceptable timely condition. 
 
All SAEs need to be followed until the event is resolved (with or without sequelae). The safety officer 
or designee of this clinical investigation will decide if more follow up information is needed in case the 

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Adverse Device Effect (ADE’s) are adverse events related to the use of an investigational 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 investigational 
medical device. This definition includes any event resulting from use errors or from intentional misuse 
of the investigational medical device. 
Serious Adverse Device Effects (SADE): adverse device effects that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Unanticipated Serious Adverse Device Effect (USADE): Unanticipated serious adverse device effect 
(USADE) is a serious adverse device effect which by its nature, incidence, severity or outcome has not 
been identified in the Investigators Brochure or Instruction For Use. 
Device Deficiency: Inadequacy of an investigational 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 user error and inadequate 
labeling. 
If a device deficiency occurs, especially that could have led to a SAE, the investigator must report the 
event as per MEDDEV and to the sponsor by completing the event within 24hours after awareness into 
the eCRF. 
If a device deficiency is detected or suspected, it should be documented on the appropriate eCRF and 
the device must be returned according to the Sponsor’s instructions. 
If the device deficiency is associated with any SAE (SADE/ USADE) or if a device deficiency occurs that 
could have led to a SADE if suitable action had not been taken or, intervention had not been made 
or, if circumstances had been less fortunate or a new findings/updates in relation to already 
reported events, the investigator must report the event and device deficiency within 24 hours of 
awareness to the Sponsor. 
The sponsor will review all reported device deficiencies and will determine and document in writing 
whether they could have led to a SADE and report accordingly to the competent and regulatory 
authorities, and REB/IRB/EC requirements. In case of disagreement between the sponsor and the 
principal investigator(s), the sponsor shall communicate both opinions to the concerned parties. 
Event reporting to relevant competent authorities in accordance with the jurisdictional regulations 
will occur by the sponsor and/or by the investigator, depending upon the local requirements and will 
be done in EU per MEDDEV 2.12/1 guidelines for CE-marked devices manufactured by Biosense 
Webster and per MEDDEV 2.7/3 guidelines for non CE-marked devices manufactured by Biosense 
Webster. Device Deficiency of concomitant CE marked devices 

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If a device deficiency of a CE marked device manufactured or distributed by the sponsor and 
registered locally has occurred, the event has to be notified immediately to the sponsor via 
Biosense Webster regular complaints handling process and procedures. 
In Europe, if this event is considered as an incident according to the definition given in the MEDDEV 
2.12/1 guidelines, the sponsor will notify the incidents to the competent authorities or local 
regulatory authorities, according to the regulatory requirements and company procedures applicable 
for CE marked medical devices. 
Documentation/Follow-up Reporting 
All AE/SAE must be monitored until they are adequately resolved or explained, including submission of 
follow-up reports to the sponsor or designee as soon as the information becomes available. 
Additional documentation may be requested by the Sponsor or designee, including but not limited to, 
a written subject narrative detailing the clinical course of the AE/incident, a copy of any 
correspondence with the local REB/IRB/EC, hospital records, death certificate, and an autopsy report, if 
available. 
 
Reporting Requirements to Sponsor and Regulatory/ Competent Authorities 
All serious AE (SAE/SADE), whether or not they are related to the device or procedure, and 
Unanticipated Serious Adverse Device Effect (USADE) must be reported to the Sponsor or designee 
and entered into the eCRF within 24-hours of awareness by the clinical 
investigation site personnel. 
 
15 STATISTICAL CONSIDERATIONS 
15.1 Sample Size 
This is a feasibility study of safety and effectiveness in which the sample size of the clinical 
investigation is intended to provide preliminary estimates of these 2 aspects. Enrollment in the clinical 
investigation will be approximately 40-70 evaluable subjects. 
15.2 Analysis Populations 
The following analyses populations will be used to complete the analyses of the data: 
Safety Subject Population: The safety subject population will include all enrolled subjects who 
have the RHYTHMFINDER™ 192 Catheter inserted, regardless if cartofinder guided ablation 
was performed 
Evaluable Subject Population: The evaluable subject population will include all enrolled subjects who 
have the RHYTHMFINDER™ 192 Catheter inserted and where cartofinder guided ablation was 
performed 
 

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15.3 Statistical Methods 
Descriptive statistics and two-sided 95% confidence intervals will be presented for the effectiveness 
and safety endpoints. No formal statistical hypothesis and inferential statistics will be formulated and 
performed. Analyses of all endpoints will be performed in the proposed analysis populations excluding 
the subjects with missing outcomes.  
15.3.1 Safety 
Acute safety outcome will be reported as the number of primary adverse events and the number of 
subjects experiencing primary adverse events (within 7 days of procedure, with exception for PV 
stenosis and AE fistula (Table 14.4). 
Incidence of (S)AEs during follow-up will be reported as the number of (S)AEs and the number of 
sibjects experiencing (S)AEs. The number and percentage of subjects with (S)AEs will be summarized 
overall and by AE type, seriousness, severity, causality, anticipated or not and outcome. Listing of 
(S)AEs will also be provided.  
 
The safety population (SP) will be used as the analysis population. 
 
15.3.2 Effectiveness 
Effectiveness outcomes includes  freedom from documented AF/AT/AFL recurrence post the 3-month 
blanking period through the 12-month follow up, conversion of atrial fibrillation to normal sinus 
rhythm or atrial tachycardia post CFGA or post overall ablation procedure with or without 
cardioversion, and entrance block confirmation post PVI.  The number and percentages of subjects 
with effectiveness endpoints and the corresponding two-sided 95% binomial confidence intervals will 
be presented. Listing of effectiveness outcomes will be provided. 
The evaluable population (EP) will be used as the analysis population for all effectiveness endpoints. 
 
15.3.3 Investigational Device Performance 
Investigational device performance will be reported as the number of ablation targets identified and 
the maximum % of active electrodes. Investigational device performance will also be reported by 
means of survey questions. Listings of survey answers/scoring will also be provided. These analyses will 
be conducted in the evaluable population (EP). 
15.3.4 Procedural Data 
Procedural data such as procedure duration, mapping duration, fluoroscopy time/dose, power, contact 
force,will be summarized with descriptive statistics and listed. These analyses will be conducted in the 
evaluable population (EP). 
 

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15.4 Missing Data Handling 
Missing data will be queried for reasons and will not be imputed. 
 
16 ADMINISTRATIVE PROCEDURES AND RESPONSIBILITIES 
The clinical investigation will be conducted in compliance with this protocol, and according to ISO 
14155: 2011, MEDDEV 2.7/3, the medical device directive 93/42/EC and amendments, the 
Declaration of Helsinki, the International Conference on Harmonization (ICH) Harmonized 
Tripartite Guideline of Good Clinical Practice (E6) and in compliance with national regulations. 
16.1 Research Ethics Board/Institutional Review Board/Ethics Committee 
This  protocol  and  the  informed  consent  must  be  reviewed  and  approved  by  the appropriate 
REB/IRB/EC and the Competent Authorities/Health Authorities where the clinical investigation is 
to be conducted before enrollment of subjects. Any additional requirements imposed by the 
REB/IRB/EC or regulatory authority shall be followed, if appropriate.  The sponsor and the 
REB/IRB/EC must approve in writing any changes to the protocol that affect the rights, safety, or 
welfare of the subjects, or may adversely affect the validity of the clinical 
investigation. 
A  signed  copy  of  the  REB/IRB/EC  Approval  Form  and  a  signed  copy  of  the REB/IRB/EC 
approval letter addressed to the investigator must be submitted to the sponsor certifying clinical 
investigation approval before commencement of subject enrollment. Investigators are responsible 
for submitting and obtaining initial and continuing review (per local regulations) of the clinical 
investigation by their REB/IRB/EC. 
16.2 Monitoring of the Study 
Monitoring will be conducted throughout the course of this study according to the Monitoring Plan 
and sponsor standard operating procedures. 
Monitoring visits will be conducted to oversee the progress of the study and verification of the 
following: 
- the rights and wellbeing of the subjects are protected; 
- the study is conducted according to Good Clinical Practices (GCP) and local regulations; 
- the protocol and applicable amendments are followed; 
- the recorded data are accurately represented. 
The sponsor and/or designee will perform on-site monitoring visits as defined in the study 
Monitoring Plan. Each visit will encompass activities such as verification that all subjects have signed 
the study’s ICF, confirmation that procedures are being followed, completion of appropriate source 
document verification, anonymized CARTO files downloads, and identification of and action taken to 
resolve any issues or problems with the study. 

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The sponsor may request further documentation such as investigator and/or EP lab procedure notes 
when needed or when complications 
or device deficiencies are observed. To this end, the investigator 
and institution must permit inspection of the study files and subjects’ eCRFs by Sponsor personnel. 
16.3 Management of Protocol Amendments 
All instructions described in this study protocol are to be followed.  If an amendment is required, it 
must be made in written form and receive approval from all persons and authorities who approved 
the original protocol.  Administrative changes (do not effect subjects benefits/risks ratio) may be 
inserted with abbreviated approval. All amendments will be distributed to all original protocol 
recipients. 
16.4 Adherence to the Protocol 
The investigator is responsible for ensuring the clinical investigation is conducted in accordance with 
the procedures and evaluations described in this protocol (see Investigator Signature Page at the 
beginning of this protocol). 
Deviations from the protocol shall not be made except in a medical emergency, when the intent is to 
reduce immediate risk to the subject. In such cases, the sponsor, REB/IRB/EC, regulatory authorities, 
and insurance company, as appropriate, should be notified in accordance with local requirements. 
Changes to the protocol may be made only when a written protocol amendment provided by the 
sponsor has been signed by the investigator and approved by the REB/IRB/EC and applicable 
regulatory agencies in accordance with local requirements and ISO 14155. 
The sponsor is responsible for submitting progress reports, including safety summary and deviations, 
when requested, to all reviewing ECs and the regulatory authorities. 
16.5 Records and Responsibilities 
16.5.1 Study Early Termination, Suspension of the Study 
The sponsor may suspend or prematurely terminate either the study in an individual study site or the 
entire study for significant and documented reasons including any significant and documented 
reasons as deemed appropriate 
by the sponsor. 
A principal investigator, REB/IRB/EC, or regulatory authority may suspend or prematurely terminate 
participation in the study at the study sites for which they are responsible. 
If suspicion of an unacceptable risk to subjects arises during the study, or when so instructed by the 
REB/IRB/EC or regulatory authorities, the sponsor shall suspend the study while the risk is 
assessed. The sponsor shall terminate the study if an unacceptable risk is confirmed. 
The sponsor shall consider terminating or suspending the participation of a particular study site or 
investigator in the study if monitoring or auditing identifies serious or repeated deviations on the 
part of an investigator. 

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If suspension or premature termination occurs, the terminating party shall justify its decision in 
writing and promptly inform the other parties with whom they are in direct communication. The 
principal investigator and sponsor shall keep each other informed of any communication received 
from either the REB/IRB/EC or the regulatory authority. 
If, for any reason, the sponsor suspends or prematurely terminates the study at an individual study 
site, the sponsor shall inform the responsible regulatory authority as appropriate and ensure that the 
REB/IRB/EC is notified, either by the principal investigator or by the sponsor. If the suspension or 
premature termination was in the interest of safety, the sponsor shall inform all other principal 
investigators. 
If suspension or premature termination occurs, 
a.   the sponsor shall remain responsible for providing resources to fulfill the obligation from the 
Protocol and existing agreements for following up the subjects enrolled in the study, and 
b.   the principal investigator or authorized designee shall promptly inform the enrolled 
subjects at his/her study site, if appropriate, and 
(Note: the method and the timing of this communication will depend on the circumstances 
and the perceived risks) 
c.  arrangements will be made for the return of all devices supplied and other material in 
accordance with the sponsor procedures for the study 
When the sponsor concludes an analysis of the reason(s) for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, the sponsor shall inform 
the principal investigators, the REB/IRB/ECs, and, where appropriate, the regulatory authority of the 
rationale and provide them with the relevant data supporting this decision. 
Concurrence  shall  be  obtained  from  the  REB/IRB  /ECs  and,  where  appropriate, regulatory 
authorities before the study resumes. 
If subjects have been informed of the suspension, the principal investigator or authorized designee 
shall inform them of the reasons for resumption. 
In case of early termination of the clinical investigations, the sponsor or his authorized 
representative as applicable will notify the relevant regulatory agencies , competent authorities and 
EC of the end of the clinical investigation, with a justification in case of early termination. In the case 
of early termination of the clinical investigation on safety grounds this notification shall be 
communicated to all concerned regulatory agencies competent authorities and REB/IRB /EC’s   as 
applicable and directed by the Medical Device Directive 93/42/EC and amendments 
 
16.5.2  Investigator Records 
The investigator is responsible for the preparation, review, signature, and maintenance of the records 
cited below. 

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 REB/IRB/EC approval letter, including approved ICF document, with associated 
correspondence 
 REB/IRB/EC membership 
list 
 Signed Clinical Study Agreement 
 Clinical investigation protocol/Investigational Plan and all amendments, and CRF 
 Signed original copy of the Investigator Agreement and CV 
 Correspondence relating to the clinical 
investigation 
 CV for all Sub-Investigator(s) 
 Investigational site training records 
 All logs including patient ID log, screening 
log, enrollment 
log, as applicable 
 Site personnel delegation of authority/responsibility 
 Clinical Monitor/Site 
Visit sign-in log 
 Reports (e.g., annual reports, final reports from 
investigator and Sponsor) 
The following records must be maintained for each subject enrolled in the clinical investigation: 
 Subject’s  case  history  records  including,  but  not  limited  to  medical  history, procedure 
dates, and dates of follow-ups 
 Electronic data, if applicable 
 Source documents (Imaging, ECGs, Pregnancy test, …) 
 Signed 
informed consents 
 All completed CRFs 
 Supporting documentation of any AE 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 clinical investigation. 
The sponsor reserves the right to secure data clarification and additional medical documentation on 
subjects enrolled in this clinical 
investigation. 
16.5.3 Investigator Responsibilities 
 Obtain REB/IRB/EC approval, 
if applicable 
 Supply  the  Sponsor  with  a  current  curriculum  vitae  and  medical  licenses  (if 
applicable) for  any colleague(s) 
involved in the study 
 Obtain informed consent form and enroll patients 
 Perform medical procedures 
 Order all tests required by the study protocol 
 Adhere to the study protocol 
 Follow subjects until the end of the study protocol 
 Complete eCRFs on time, completely and accurately 

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 Allow the Sponsor direct access to source documents to perform monitoring duties, and to 
perform audits 
 Maintain records and provide reports according to the local legislation/regulations 
 Share all relevant study-related 
information with colleagues 
involved 
in this study 
 Inform the appropriate entities (e.g., Sponsor, REB/IRB/EC in a timely manner regarding 
the occurrence of any AEs and/or device deficiencies. 
16.5.4 Sponsor Responsibilities 
 Selection of the study investigators 
 Selection of appropriately qualified and trained individuals, including monitors, to 
conduct the study 
 Development and, if applicable, modifications of protocol and eCRFs 
 Obtain study contracts with investigators/hospitals, CROs and other involved 3
rd 
parties 
 Development and/or approval of an adequate informed consent 
form 
 Ensure that appropriate training/information is provided to the study investigators and 
staff 
 Data and site monitoring 
 Database 
input, management and maintenance 
 Inform 
investigator of his/her responsibilities 
 Ensure that all AEs are reported by the study investigators and where appropriate, are 
reported to the other investigators and relevant regulatory authorities 
 Implement 
insurance coverage prior enrolment of patients 
 Obtain applicable regulatory approval prior to enrollment of subjects 
 Report deviations from the protocol as appropriate. 
 Prepare written required reports and a final clinical study report and provide to ECs 
and regulatory authorities as applicable. 
16.5.5 Document Retention 
Records and reports will remain on file for a minimum of five (5) years (unless otherwise instructed by 
local regulatory and/or institutional requirements) after completion of the clinical investigation. The 
investigator must notify the Sponsor before destroying any clinical 
investigation records. 
16.6 Regulatory and Ethical Obligations 
Biosense Webster will determine the appropriate local, national, and regional regulatory approval(s) 
that need to be obtained to conduct this clinical investigation according to appropriate legislation 
and guidance documents. 

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17 DATA MANAGEMENT 
The Sponsor or designee will perform all data management activities for this clinical 
investigation. These activities include development and validation of a clinical database, into which 
all clinical investigation data will be entered. The Sponsor or designee will be responsible for ensuring 
overall 
integrity of the data and database. 
17.1 Data Collection 
Electronic Case Report Forms (eCRF) will be used to collect all subject data during this clinical 
investigation. The eCRF will be developed to capture the information outlined in this protocol. Data 
collected on the eCRFs will be analyzed as defined in the clinical investigation protocol. 
Modification of the eCRF will only be made if deemed necessary by the sponsor. All CARTOFINDER™ 
maps created during the procedure will be downloaded/ extracted and an anonymized copy 
provided to the sponsor for further evaluation. 
 
17.2 Device Accountability 
The sponsor will keep records of all devices / materials supplied 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 that each device was used in the study and disposition 
information regarding disposal or return 
to the sponsor. 
The Device Accountability Log shall record the following information: 
 Date of receipt 
 Person who received the devices 
 Quantity received 
 Serial/lot numbers 
 Date device was used (if applicable) 
 Subject ID on whom device was used (if applicable) 
 Date of device return 
 
17.3 Device Returns 
All investigational study devices will be returned to the sponsor.   Any suspected malfunctioning 
device or device associated with an adverse event (device related or possibly device related) from 
the sponsor will undergo a thorough complaint analysis and must be properly documented on the 
case report form (eCRF). All returned devices must be properly decontaminated per hospital policy 
and properly labeled with the following: 
 Subject 
identification number 
 Date of use/event 

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 Return type (defective, non-defective, or adverse event) 
All tracking information must be retained in the event the package has been lost and requires 
tracking. 
 
17.4 Data Reporting 
The investigator, or a designated individual, is responsible for ensuring that clinical investigation data 
are properly recorded on each subject’s eCRF and related documents. The investigator is required to 
electronically sign the eCRF on the appropriate pages to verify that he/she has reviewed and attests 
to the correctness of the recorded data. Completed eCRF will be monitored by the sponsor 
personnel, or an appropriately qualified and trained designee, at regular intervals throughout the 
clinical investigation. The investigator and institution must permit the inspection of any clinical 
investigation- related documentation and eCRF by clinical investigation representatives, responsible 
government agencies, or both. 
All eCRF data should be entered by the designated site personnel within approximately 14 days of 
the subject visit. For AE reporting, refer to the Adverse Event Reporting Requirements and 
timelines within this clinical 
investigation protocol. 
 
17.5 Source Documentation 
Source documents will serve as the basis for monitoring the eCRF. Source documents may include 
subject’s medical records, hospital charts, clinical charts, the investigator’s subject clinical 
investigation files, admissions and discharge summaries, as well as the results of diagnostic tests 
such as X-rays, laboratory tests, and electrocardiograms. 
If no standard hospital or office document exists to capture information that may be unique  to  this  
clinical  investigation, a  worksheet  may  be  developed  to  record  this information, which may be 
signed by the site and serve as the source document for unique clinical 
investigation data. 
Electronic subject records will be considered source documents on the condition that the hospital’s 
database is a validated system. If this is not the case, electronic records will have to be printed and 
added to the subject’s paper file. A print-out 
of an eCRF cannot be used as source documentation. 
Regulations require that investigators maintain information in the subject’s medical records, which 
corroborate data collected on the eCRF. In order to comply with these regulatory requirements, at 
minimum, the following is a list of information that should be maintained on source documentation: 
 Medical history/physical condition of the clinical investigation subject before involvement 
in the clinical investigation sufficient to verify protocol selection criteria (if not already 
present). 

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 Dated  and  signed  notes  on  the  day  of  entry  into  the  clinical  investigation including 
the name of the clinical investigation sponsor (Biosense Webster), protocol number, clinical 
site identifier, subject number assigned and a statement that consent was obtained. 
 Dated and signed notes from each clinical investigation visit with reference to the eCRF for 
further 
information, if appropriate (for specific results of procedures and examinations). 
 AEs reported and their resolution, including supporting documents such as 
discharge summaries, EP lab reports, ECGs, laboratory results, etc. 
 Notes regarding protocol-required medication and prescription medications taken during the 
clinical investigation (including start and stop dates). 
 Clinical investigation subject’s condition upon completion of or withdrawal from the clinical 
investigation. 
17.6 Data Verification and Review 
All eCRF will be subjected to automated and manual validation checking for omitted data, gross 
data inconsistencies, and timeliness of reporting. The sponsor or designees will employ a clinical 
investigation database on a server, available to site and sponsor personnel over an Internet 
connection. Periodic analysis of data (across cases) will be performed in order to examine the 
expected distributions of data, and to identify outliers for possible data entry errors. For first cases at 
each site, the investigators and/ or sponsor may wait for the result of the case analysis before 
enrolling the next patient in this study site. 
17.7 Final Data Analysis 
All exported datasets for analyses will undergo a final data review before final database lock. Once all 
critical data are monitored and locked, the final analyses of clinical investigation data will be 
performed. 
17.8 Confidentiality and Protection of Clinical Investigation Data 
To ensure confidentiality, protection, and attribution of the clinical investigation data, only 
trained and authorized sponsor and site personnel will be assigned unique user accounts and 
passwords to access the clinical investigation database. Each user account is designed to allow 
appropriate user rights and access level with the clinical investigation database system. 
17.9 Publication Policy 
Publication of clinical investigation results will be coordinated between the sponsor or designee. 
Authorship will be determined by the sponsor before development of any manuscript and in 
agreement with the participating Principal Investigators. 
 

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18 RISK/BENEFIT ANALYSIS 
18.1 Potential Risks 
A degree of risk exists with the LAT Algorithm not providing accurate information on target ablation 
sites. This is directly related to lack of information when recordings are collected potentially due to 
insufficient catheter contact. Investigators (EPs) may be asked to take multiple maps for comparison 
but as well as have other modalities such as the EP recording system to observe real time catheter 
signals and fluoroscopy to determine identified target areas for clinical relevance and risk. 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%) [16, 
17, 18, 19, 20, 21, 22, 23]. 
Do not reprocess, resterilize, or reuse. This device is packaged and sterilized for single use only. 
Reprocessing, resterilizing, or reusing may compromise the structural integrity of the device and/or 
lead to device failure that in turn may result in patient injury, illness, or death. Also, reprocessing or 
resterilization of single use devices may create a risk of contamination and/or cause patient infection 
or cross-infection, including, but not limited to, the transmission of infectious disease(s) from one 
patient to another. Contamination of the device may lead to injury, illness, or death of the patient.  
Other potential complications, which may result from catheter insertion and manipulation as part of 
the prerequisite electrophysiology trial and mapping procedure, include: Allergic reaction to the 
local anesthetic, sedatives, X-ray dye, heparin, protamine, or other agents administered during the 
procedure (risk < 1%) [21, 24-27] 
Arterial or venous injury, including arterial dissection, thrombosis, occlusion or hemorrhage at the 
catheter insertion sites or at other sites along the vessels (risk < 1%) [16, 17]. These types of injuries 
may cause hemorrhage, hematoma, or ischemic injury to an extremity or major organ. Hemorrhage 
as a result of anticoagulation (risk < 0.5%), which may require transfusion [16, 17]. 
Potential risk of entanglement/and or entrapment. When the RF-192 basket catheter is within the 
proximity of the tricuspid valve or mitral valve, cautions need to be applied to avoid entanglement 
with chordae tendineae.  
Infection at the catheter insertion site or systemic infection, including endocarditis and septic  
emboli (risk < 0.5%) [16, 17], can be minimized by using standard aseptic technique and, when 
indicated, 
by the use of antibiotic agents. 
Additional contraindications for device use may include: hemodynamic instability, bacteremia, 
coagulopathy, prosthetic tricuspid valve, intra-atrial or venous thrombosis, and pregnancy (refer to 
the IFU for a complete 
list of contraindication for the device). 
A full list of potential adverse events that are reasonably anticipated to occur as a result of the use 
of the clinical investigation device during the cardiac electrophysiology procedure include all of the 
events noted in any clinical study for these types of devices to date (refer to section 14) 

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18.2 Methods to Minimize Risk 
The criteria for subject selection, methods, personnel, facilities, and training that have been 
specified in this study are intended to minimize the risk to subjects undergoing the mapping 
procedure. Subjects will be screened carefully prior to enrollment in the study to ensure compliance 
with the inclusion and exclusion criteria. The exclusion criteria have been developed to exclude 
subjects with a medical history or condition that increases their risk of adverse events. 
Only investigators skilled in intra-cardiac mapping with the use of a multi-electrode (basket) catheter 
will be selected for participation in this study. The mapping procedures required for this study will 
be performed in electrophysiology laboratories with the assistance of skilled nurses and 
technicians. Additionally, safety data will be collected and evaluated regularly during enrollment by 
an unbiased investigator safety review committee, and all adverse events and device deficits will 
be reported to the study sponsor. 
 
18.3 Potential Benefits 
In patients with complex arrhythmias, elimination or amelioration of symptoms is a major 
driving force for therapy. The CARTOFINDER™ System and LAT Algorithm is designed to analyze the 
collected signals (electrical signals of the heart captured by the basket catheter) and show in a 
graphical display the specific locations in the heart which could sustain the arrhythmia. The RF192 
Catheter is intended to simultaneously collect multiple 
 intracardiac signals and 
facilitate faster mapping of the atrial chambers of the heart using CARTO
® 3 EP Navigation System. 
The CARTOFINDER™ Device provides voltage analysis of multiple, simultaneous ECG signals. A 
period of ECG recordings can be selected for analysis with a CARTOFINDER™ Device algorithm. The 
algorithm generates a 4D map display of IC voltage signal measurements over time to assist the 
investigators with the better understand the voltage activation patterns for analysis and therapy 
planning. 
Through the simultaneous and sequential collection of these intra-cardiac signals and the mapping 
procedure, the RF192 Catheter might aid in the diagnosis of these complex atrial arrhythmias. The 
degree of risk of the electrophysiological procedure and the potential benefit of the treatment of 
complex arrhythmias should be determined by a qualified investigator. The information gathered 
during the conduct of this study may be of benefit in the future for the treatment of patients with 
complex arrhythmias and in particular persistent AF. 

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19 REFERENCES 
 
 
 
1  
Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS expert consensus statement 
on catheter and surgical ablation of atrial fibrillation: recommendations for patient 
selection, procedural techniques, patient management and follow-up, definitions, 
outcomes, and research trial design. Heart Rhythm 2012;9:632–96. 
 
2  
Cheema A, Vasamreddy CR, Dalal D, et al. Long-term single procedure efficacy of catheter 
ablation of atrial fibrillation. J Interv Card Electrophysiol 2006;15:145–55. 
 
3  Weerasooriya R, Khairy P, Litalien 
J, et al. Catheter ablation for atrial fibrillation: 
are results maintained 
at 5 years of follow-up? 
J Am Coll Cardiol 2011;57:160–6. 
 
4.  Brooks SC, Schmicker RH, Rea TD, et al. Out of hospital cardiac arrest frequency and 
survival: evidence for temporal variability. Resuscitation 2010;81: 175-81 
 
5  Tilz RR, Chun KR,Schidt B, et al. Catheter ablation of long standing pesistant atrial 
fibrillation: a lesson from circumferential pulmonary vein isolation. J Cardiovasc 
Electrophysiol 2010;21:1085-93 
 
6  Ouyang F, Antz M, Ernst S, et al. Recovered pulmonary vein conduction as a dominant 
factor for recurrent atrial tachyarrhythmias after complete circular isolation of the 
pulmonary veins: 
lessons from double 
lasso technique. 
Circulation 
2005;111:127–35. 
 
7  Verma A, Kilicaslan F, Pisano E, et al. Response of atrial fibrillation to pulmonary vein 
antrum isolation is directly related to resumption and delay of pulmonary vein 
conduction. 
Circulation 
2005;112:627–35. 
 
8  
Haissaguerre M, Sanders P, Hocini M, et al. Catheter ablation of long-lasting 
persistent atrial fibrillation: critical structures for termination. J Cardiovasc 
Electrophysiol 2005;16:1125–37. 
 
9  
Sawhney N, Anand K, Robertson CE, Wurdeman 
T, Anousheh R, Feld GK. 
Recovery of mitral isthmus conduction leads to the development of macro-reentrant 
tachycardia after left atrial linear ablation for atrial fibrillation. Circ Arrhythm 
Electrophysiol 2011;4:832–7. 
 
10  Nattel S. New ideas about atrial fibrillation 50 years on. Nature 
2002;415:219 
–26. 
 
11  Allessie MA, de Groot NM, Houben RP, et al. The electropathological substrate of 
longstanding persistent atrial fibrillation in patients with structural heart disease: 
longitudinal 
dissociation. 
Circ Arrhythm 
Electrophysiol 
2010;3:606 
–15. 
 
12  Haissaguerre, M., Jais, P., Shah, D. C., et al. (1996). Right and left atrial 
radiofrequency catheter therapy of paroxysmal atrial fibrillation. Journal of 

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Cardiovascular Electrophysiology, 7(12), 1132–1144. 
 
13  Sanyiv MN, Baykaner T, Clopton P, et al. Ablation of Rotor and Focal Sources reduces 
late recurrence of AF compared with Trigger Ablation alone. J of Am College of 
Cardiology, 2014 Vol 63, 17. 
 
14  Atul V, Sanders P, Macle L, et al. Substrate and Trigger ablation for reduction 
of 
Atrial Fibrillation. Am Heart J,2012; 164:1-6.e6. 
 
15. January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE, Conti JB, Ellinor PT, 
Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy 
CW. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: 
a report of the American College of Cardiology/American Heart Association Task Force on 
Practice Guidelines and the Heart Rhythm Society. Circulation 2014;129 
 
16  Huang SKS, Wilber DJ [eds]: Radiofrequency Catheter Ablation of Cardiac Arrhythmias: 
Basic Concepts and Clinical Applications, 2nd ed. Grouponk, NY: Futura Publishing 
Company, Inc. [2000]; Lin AC, Wilber D, Complications Associated With Radiofrequency 
Catheter Ablation. Pages 737-746. 
 
17  Scheinman MM, Huang S, [2000] The 1998 NASPE Prospective Catheter Ablation 
Registry. PACE 23:1020-1028. 
 
18 Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Natale A, 
Packer D, Skanes A, Ambrogi F, Biganzoli E [2010] Updated worldwide survey on the 
methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ 
Arrhythm Electrophysiol 3:32-38. 
 
19  Kovoor P, Ricciardello M, Collins L, Uther JB, Ross DL, [1998] Risk to Patients From 
Radiation Associated With Radiofrequency Ablation for Supraventricular Tachycardia. 
Circulation 98:1534-1540. 
 
20  Nahass GT [1995] Fluoroscopy and the Skin: Implications for Radiofrequency 
Catheter Ablation Am J Cardiol 76:174-176. 
 
21  Cox B, Durieux ME, Marcus MA, [2003] Toxicity of Local Anaesthetics. 
Best 
Pract Res Clin Anaesthesiol.17: 111-136. 
 
22  Gerstenfeld EP, Guerra P, Sparks PB, Hattori K, Lesh MD, [2001] Clinical Outcome 
After Radiofrequency Catheter Ablation of Focal Atrial Fibrillation Triggers. J 
Cardiovasc Electrophysiol 12:900-908. 
 
23  Takahasi A, Lesaka Y, Takahasi Y, Takahasi R, Kobayashi K, Takagi K, Kuboyama O, 
Nishimori T, Takei H, Amemiya H, Fujiwara H, Hiraoka M, [2002] Electrical Connections 
Between Pulmonary Veins; Implication for Ostial Ablation of Pulmonary Veins in Patients 
with Paroxysmal Atrial Fibrillation. Circulation 
105:2998-3003. 

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24  Mertes PM, Laxenaire MC, [2002] Allergic Reactions Occurring During 
Anaesthesia. Eur J Anaesthesiol. 19:240-262. 
 
25  Morcos SK, Thomsen HS, Webb JA; Contrast Media Safety Committee of the 
European Society of Urogenital Radiology [2001] Prevention of Generalized 
Reactions to Contrast Media: A Consensus Report and Guidelines. Eur Radiol 
11:1720-1728. 
 
26  Gruchalla RS, [2003] 10. Drug Allergy. J Allergy Clin Immunol. 111:S548-S559. 
 
27  Bick RL, Frenkel EP, [1999] Clinical Aspects of Heparin-Induced Thrombocytopenia and 
Thrombosis and Other Side Effects of Heparin Therapy. Clin Appl Thromb Hemost. 
5:S7-S15.  58. 
 
28. Leon MB 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 57:253-269. 

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20 ATTACHMENTS  
20.1 Attachment A: 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 (investigational) whether or not 
related 
to the investigational 
product. 
 
This definition includes events related to the investigational medical 
device and/or the comparator, and events related to the procedure 
in which 
the investigational 
device 
was used. 
 
Adverse Device 
Effects 
(ADE’
s) 
 
Adverse events related to the use of an investigational 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 investigational medical device. 
This definition includes any event resulting from use errors or from 
intentional 
misuse 
of the investigation 
medical 
device. 
 
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 investigational 
medical 
device and/ or intervention 
procedure. 
 
 
Atypical Flutter 
 
Macroreentrant circuits within the atria where activation rotates 
around large obstacles that does not meet the criteria for Typical 
Flutter. 
 
Baseline Rate 
 
Is the recorded rate from the subject demonstrating the ventricular 
response of the subjects 
arrhythmia. 

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Term 
 
Definition 
 
 
Cycle 
Length 
Measurement 
 
Cycle Length will be measured by placing a multielectrode  catheter 
(connected to the recording system) in the CS  calculating the average 
CL 
over 10 repetitive 
cycles. 
 
 
 
 
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. 
 
High-burden 
paroxysmal 
AF 
 
AF episodes lasting less than 30 days. Episodes may terminate 
spontaneously 
or may be terminated 
via cardioversion. 
 
Longstanding 
persistent 
AF 
 
Continuous 
AF of > 12 months 
duration 
 
Organized 
AF 
 
When observing the surface leads, an organized activation is considered 
present if discrete atrial complexes, 
separated 
by an isoelectric 
baseline, 
were seen during three or more cycles over at least 30 msec and have 
variability in beat-to-beat cycle length, electrograms 
mainly in surface P-
wave morphology. This includes other atrial rates recorded/observed in 
other portions 
of the atrium. 
 
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. 

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Persistent 
AF 
 
Persistent 
AF is defined 
as continuous 
AF that is sustained beyond 
7 days. Episodes of AF in which a decision is made to electrically or 
pharmacologically 
cardiovert 
the patient after ≥ 48 hours of 
AF, but prior 
to 7 days, should 
also 
be classified 
as persistent 
AF episodes. 
 
 
Rate of Slowing 
 
Rate of slowing for the overall mean atrial fibrillation rate is defined by 
a decrease in cycle length of the ventricular/atrial 
rate when compared 
to baseline 
ventricular/atrial 
rate for each subject. 

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Term 
 
Definition 
 
Serious adverse 
event 
(SAE) 
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 
 
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. 
 
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.