A Prospective, Multicenter, Single Arm With Performance Goal Study to Evaluate Safety and Effectiveness of Multi-electrode Circular IRE Catheter and Multi-Channel IRE Generator in Paroxysmal AF
Phase: NA
Conditions: Refractory Paroxysmal Atrial Fibrillation
Sponsor: Biosense Webster, Inc.

AFIRE study
Protocol Number: BWI202107
APRIL 20, 2023 V2.2
CONFIDENTIAL 
Page 1 of 88
A prospective, multicenter, single arm with performance goal 
study to evaluate sAfety and eFfectiveness of Multi-electrode 
Circular IRE Catheter and Multi-Channel IRE Generator in 
paroxysmal AF
In short: AFIRE study
Name of investigational 
medical device
BWI IRE system:
Model/specification
See section 4.2
Management category of 
investigational medical 
device
Class III medical device requiring clinical trial approval: Yes No 
Predicate product in China: Yes  No 
Protocol No.
BWI202107
Protocol version No.
2.2
Protocol version date
Apr 20, 2023
Clinical study site
The First Affiliated Hospital of Zhengzhou University
Investigator
Jianzeng Dong
Sponsor
Biosense Webster, Inc., a division of Johnson & Johnson 
Agent
Johnson & Johnson Medical (Shanghai) Ltd.
This study protocol contains the confidential information and is only provided for 
use by clinical investigators. This document remains the exclusive property of the 
Johnson & Johnson Medical. The undisclosed information herein should not be 
disclosed without the prior written approval of Johnson & Johnson Medical. This 
document is only provided for use by interested parties.
CCI
NCT05552963

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Protocol Number: BWI202107
APRIL 20, 2023 V2.2
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Revision History
Version
Version date
Change description
V 1.0
Mar 10, 2022
Original Document
V 2.0
Jun 13, 2022
Update contents
Anticoagulation 
protocol prior 
to procedure 
related 
amendments
The exclusion criteria listed in the Study Synopsis and 6.1.4.2 are modified 
as follows
1.
In Item 6 of Exclusion criteria, “Documented left atrium (LA) thrombus 
within 48 hours prior to the index procedure by one of the following 
modalities TEE, ICE, CT, MRI” was updated to “Documented left 
atrium (LA) thrombus within 48 hours prior to the index procedure by 
TEE or CT (in case of TEE intolerance), or by ICE prior to the 
transeptal puncture by ICE during procedure”.
2.
In Item 10 of Exclusion criteria, the content “History of a documented 
thromboembolic event (including TIA) within the past 12 months” was 
updated to “History of a documented thromboembolic event (including 
TIA) within the past 12 months, or history of a documented left atrial 
appendage (LAA) thrombus”.
3.
The following exclusion criteria were added from 31 to 34:
31. History of massive haemorrhage within the past 6 months.
32. Blood test anomaly: HGB≤90 g/L or PLT <100*109 /L.
33. Liver function anomaly: Cirrhosis or bilirubin > 2 times the upper 
limit of the normal value or transaminase anomaly: AST/ALT/ALP > 3 
times the upper limit of the normal value.
34. Renal function anomaly: Dialysis, kidney transplant, Cr > 2.26 
mg/d or > 200 µmol/L, CCR < 30 mL/ (min*1.73 m2).
6.3.1 Medication use, PRIOR to the procedure: “Uninterrupted warfarin 
(INR 2.0 to 3.0) or NOAC therapy should be in place at least 3 weeks prior 
to ablation procedure” was updated to “Anticoagulation therapy (NOAC 
or low molecular weight heparin) MUST be in place at least 24 hours prior 
to ablation procedure”.
6.3.1Medication use, DURING the procedure: 
1) “Administer a heparin bolus prior or post to transseptal puncture” was 
updated to “Administer a heparin bolus prior to transseptal puncture”
2) “Optimally target an ACT 350-400 seconds prior to inserting the study 
catheter and throughout the procedure.” was updated to “Optimally target 
an ACT 350-400 seconds prior to ablation and throughout the procedure” 
according to the description of procedure workflow part of section 6.5.2
6.4.2 Pre-Procedure/Baseline Assessments, Anticoagulation therapy:
1) “Uninterrupted anticoagulation management is mandatory for each 
study subject. For subjects on warfarin therapy, subjects shall be 
maintained on Warfarin for at least 3 weeks prior to treatment with an 
INR ≥ 2 (to be confirmed maximum 48h hours pre-procedure). Any INR 
<2 within 3 weeks prior to ablation will lead to exclusion of the patient or 
postponement of the study procedure. The results must be available prior 
to start of procedure” was updated to “Anticoagulation therapy (NOAC or 
low molecular weight heparin) MUST be in place at least 24 hours prior to 
ablation procedure”
2) “Imaging for detection of left atrial thrombus or other structural 
contraindications to an ablation procedure is mandatory the day before or 
the day of the ablation procedure” was updated to “Imaging for detection 
of left atrial thrombus or other structural contraindications to an ablation 

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procedure is mandatory within 48 hours prior to ablation procedure”, 
which was aligned with exclusion criteria and other parts of protocol. 
3) “The imaging method to be used for atrial thrombus detection is TEE, 
Intracardiac Echocardiography (ICE), Cardiac CT or MRI” was updated 
to “The imaging method to be used for atrial thrombus detection is TEE, 
Intracardiac Echocardiography (ICE), Cardiac CT”, which was aligned 
with exclusion criteria.
6.5.2 Study Ablation Procedure Sequence & Guidelines:
1) “Administration of heparin bolus prior or post to transseptal puncture” 
was updated to “Administration of heparin bolus prior to transseptal 
puncture”
2) “ICE catheter is strongly recommended to view the LA/PV anatomy and 
identify the contact between Circular IRE Catheter and the tissue before 
applications” was updated to “ICE catheter is REQUIRED to 1) screen for 
left atrial thrombus prior to transseptal puncture; 2) view the LA/PV 
anatomy and identify the contact between IRE Catheter and the tissue before 
applying ablation. Subjects shall be excluded from the study if left atrial 
thrombus was detected by ICE. Please refer to Exclusion criteria Item 6”.
DMC/CEC 
description was 
added
Description on DMC and CEC in Study Synopsis is added as follows: “The 
established Data Monitoring Committee (DMC) is to review the data and put 
forward recommendations according to the approved study specific 
procedure. The Clinical Events Committee (CEC) is to adjudicate the 
primary adverse events and operate following the regulations of the 
Committee.”
13.2.1 Primary Adverse Event, Description on determination is added as 
follows: “The Clinical Events Committee (CEC) is to adjudicate the primary 
adverse events and operate following the regulations of the Committee.”
New China 
GCP 
requirment
Section 13.5 Reporting procedures and contact information: “or device 
deficiency that may lead to SAE” is deleted and the procedure and time limit 
for SAE reporting is updated as per the the new version of "Medical Device 
Good Clinical Practices" (No. 28 Order) issued on May 1, 2022.
“(No.25 Order)” is deleted in section 10 and section 11.3.1.
Section 13.2.6 table 6 and table 7, per the the new version of "Medical 
Device Good Clinical Practices" (No. 28 Order) issued on May 1, 2022, the 
definition of AE outcomes and definition of causal relationship are modified.
Other minor 
updates
Chinese characters for “12 months” in Study Synopsis and section 6.1.4.1
were corrected from “12 个” to “12 个月”
Chinese characters for “6 months prior to” was modified from “前六个月” 
to “前6 个月” with same meaning in section 6.4.2.
6.5.5 Repeat Ablation Procedures:
Chinerse translation for “More than” in “More than 1 repeat procedure for 
AF/AT/AFL of unknown origin+ during the blanking period is considered a 
failure mode for primary effectiveness” was corrected from “至少1 次(at 
least 1)” to “超过1 次(more than 1)”, which was aligned with the 
definition of primary effectiveness endpoint
In Table 4 in section 13.2.1: Primary adverse events and 
description/criteria: Chinese translation for “new” in sentence of “Imaging 
evidence of new loss of viable myocardium or new regional wall motion 
abnormality” was modified from “新” to “新发” , which kept same 
meaning but more professional.

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13.2.5 Revise the IRB to EC to ensure consistent name.
V2.1
Dec 9, 2022
Updated contents
Roll-in cases 
were updated
1.
To ensure adequate roll-in cases for each investigor, maximum of roll-in 
cases was updated to 24 subjects, at most 2 roll-in cases per each 
investigator.
2.
Evaluable subjects were unchanged.
After this amendment, the total sample size was increased to maximum of 
147 subjects, including 123 evaluable non-roll-in subjects and max of 24 
roll-in subjects.
Exclusion 
criteria
Added “atrial flutter of unkown origin” to exclusion criteria #3 to be 
aligned with the requirement of “Ablation outside the PV” from session 
6.5.2, detailed as below:
“3. Patients known to require ablation outside the PV region 
(atrioventricular reentrant tachycardia, atrioventricular nodal reentry 
tachycardia, atrial tachycardia, ventricular tachycardia and Wolff-Parkinson-
White)” was revised to “3. Patients known to require ablation outside the 
PV region (atrioventricular reentrant tachycardia, atrioventricular nodal 
reentry tachycardia, atrial tachycardia, atrial flutter of unknown origin, 
ventricular tachycardia and Wolff-Parkinson-White).”
Exclusion 
criteria
Revised based on local practice suggested by China investigators in study 
initiation meeting.
“History of a documented lacunar infarction within the past 12 months” was 
revised to “History of a documented symptomatic lacunar infarction within 
the past 12 months”
Primary 
endpoint
According to protocol, DC or pharmacological cardioversion was allowed 
during blanking period. Cardioversion with Intravenous amiodarone during 
blanking period was not considered as a failure.
To be more specified,“g) Amiodarone is prescribed post index ablation 
procedure” was revised to “g) Oral amiodarone is prescribed post index 
ablation procedure”
Study Ablation 
Procedure 
Sequence & 
Guidelines
Add one caution before ablation to session 6.5.2. Study Ablation Procedure 
Sequence & Guidelines due to latest IFU amendment:
“Prior to delivering PFA energy, ensure adequate preparations are in place 
to commence emergency ventricular pacing, administer CPR, or apply other 
measures consistent with standard of care should the need arise.”
V2.2
Apr 20, 2023
Updated contents
Inclusion 
criteria
Based on the China AF guideline*, evidence update** and China clinical 
practice, the “Age 18 -75 years” was revied to “Age 18 - 80 years”.
*The description in China AF guideline 2021: “the short-term (1 year) success rate and 
complication rate were comparable between AF patients >75 years indicated for CA 
ablation and younger AF patients.”
** evidence update:
a)
Abdin A, Yalin K, Lyan E,et al. Safety and efficacy of eryoballoon ablation for the 
treatment of atrial fibrillation in elderly patients. Clin Res Cardiol, 2019, 108 
(2):167-174. DOI: 10. 1007/s00392-018-1336-x.
b)
张良锋,周根青,吴晓宇,等.高齡老年心房颤动患者行导管射频消融的安全
性和有效性研究. 中国心脏起搏与心电生理杂志,2020,34(6):549-554. 
DO1: 10. 13333/j. cmki. cjcpe. 2020. 06.008.
Study 
population
Study population description was also updated due to inclusion criteria 
chage as below.
“Patients aged 18-75 with symptomatic drug refractory PAF and indicated 

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The Biosense Webster IRE system (Circular IRE Catheter (D-1412-01-SI) and Multi-Channel IRE 
Generator(D-1417-01-I)) is for investigational device use only and is not commercially available anywhere 
in the world. “Circular IRE Catheter and IRE Generator” are internal Biosense Webster project names 
and is not intended for any other external use. The final commercial or trade name of the PFA system 
(Circular IRE Catheter and IRE Generator) may be different.
for catheter ablation” in study synopsis section, section 2.2 and section 4.3
was revised to “Patients aged 18 – 80 years with symptomatic drug 
refractory PAF and indicated for catheter ablation”
Intraprocedure 
ACT 
requirement
Based on the China AF guideline 2021 update* and China clinical practice, 
the intraprocedure ACT requirement was revised from “≥350 sec” to “≥
300 sec” and ACT test frequency was revised from “every 15-30 minutes” to 
“every12-18 minutes”. An ACT≥350 sec was recommended. The detailed
changes were listed as below:
1.
“Optimally target an ACT 350-400 seconds prior to ablation and 
throughout the procedure” in section 6.3.1 was revised to “An ACT≥
350 seconds prior to ablation and throughout the procedure is 
recommended, and An ACT≥300 seconds is required.”
2.
“An ACT below 350s requires additional bolus of heparin until a 
minimal targeted ACT of 350s is reached. It is REQUIRED to check 
ACT levels on regular basis during the procedure to ensure an ACT 
target of ≥350 seconds” in section 6.3.1 was revised to “An ACT 
below 300s requires additional bolus of heparin until a minimal 
targeted ACT of 300s is reached. It is REQUIRED to check ACT levels 
on regular basis during the procedure to ensure an ACT target of ≥
300 seconds”
3.
“REQUIRED: Confirmation of ACT ≥350 sec. PRIOR to ablation 
with the Circular IRE Catheter” in section 6.5.2 was revised to 
“REQUIRED: Confirmation of ACT ≥300 sec. PRIOR to ablation 
with the Circular IRE Catheter. An ACT≥350 sec is recommended.”
4.
“ACT MUST be targeted to be maintained ≥350 sec throughout the 
ablation” in section 6.5.2 was revised to “ACT MUST be targeted to be 
maintained ≥300 sec throughout the ablation.”
5.
“ACT must be checked every 15-30 minutes while the Circular IRE 
Catheter is in the LA” in section 6.5.2 was revised to “ACT must be 
checked every 12-18 minutes during ablation procedure”
6.
“If ACT is below 350, heparin should be administered (except for any 
safety reasons) without pausing ablation procedure” in section 6.5.2 
was revised to “If ACT is below 300, heparin should be administered 
(except for any safety reasons) without pausing ablation procedure.”
*China AF guideline 2021 update: The intraprocedural ACT recommendation was 300 to 
350 sec (I-B)
Other minor 
updates
1.
Adding missing item “physical exam” in section 6.4.2 to be aligned 
with study schedule in section 6.2
2.
“Standard 12 lead ECG” in this protocol was revised to “standard 12 
or 15 leads ECG” to be aligned with hospital routine practice.
3.
“About 37% of the total number of non-roll-in subjects” in section 
7.2.3 was revised to “about 33% of the total number of non-roll-in 
subjects” due to typing error.

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Table of Contents
Table of Contents................................................................................................. 6
List of Abbreviations......................................................................................... 10
Study Synopsis................................................................................................... 13
1.
Sponsor Information................................................................................. 20
2.
Clinical Trial Objective and Contents .................................................... 20
2.1.
Clinical trial objective....................................................................... 20
2.2.
Clinical trial contents........................................................................ 20
3.
Background Information of the Clinical Trial....................................... 21
3.1.
Disease introduction.......................................................................... 21
3.1.1. Explanation of the disease........................................................21
3.1.2. Selection of diagnosis and treatment method.........................21
3.2.
Previous Experience with Biosense Webster IRE Ablation System
............................................................................................................. 23
3.2.1. Animal Testing: Porcine Beating Heart Model (GLP Survival 
Study)..........................................................................................23
3.2.2. Summary of OUS Clinical Study.............................................27
3.3.
Product registration and the reason for clinical trial registration 
in China .............................................................................................. 28
4.
Characteristics, 
Structural 
Composition, 
Operating 
Principle, 
Mechanism of Action and Study Population of the Product ................ 28
4.1.
Characteristics of the product.......................................................... 28
4.1.1. Design features of the investigational product .......................28
4.2.
Structural composition, operating principle and mechanism of 
action of the product ......................................................................... 28
4.2.1. IRE Generator (D-1417-01-I)...................................................28
4.2.2. Circular IRE Catheter (D-1412-01-SI)....................................29
4.2.3. System Components..................................................................31
4.2.4. Required Study Devices............................................................32
4.3.
Study population ............................................................................... 33
5.
Indications, Contraindications and Precautions of the Product (From 
IFU approved by country of origin) ........................................................ 33
6.
Overall Design ........................................................................................... 33
6.1.
Study design....................................................................................... 33
6.1.1. Study objective ..........................................................................33
6.1.2. Selection of study method and justification............................33

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6.1.3. Measures for reducing and avoiding bias...............................34
6.1.4. Selection of subjects ..................................................................35
6.1.4.1.
Inclusion criteria .............................................................35
6.1.4.2.
Exclusion criteria ............................................................35
6.1.4.3.
Reasons for early termination of subjects ....................37
6.1.4.4.
Enrollment time...............................................................39
6.1.4.5.
Expected overall duration of clinical trial and 
justification ......................................................................39
6.1.4.6.
Expected duration of participation of each subject.....39
6.1.4.7.
Number of subjects required for the clinical trial .......39
6.1.4.8.
Subject Enrollment Disposition.....................................39
6.1.5. Effectiveness evaluation method..............................................40
6.1.5.1.
Description on effectiveness parameters.......................40
6.1.5.2.
Selection of method and time to evaluate, record and 
analyze the effectiveness parameters ............................42
6.1.6. Safety evaluation method .........................................................42
6.1.6.1.
Description on safety parameters..................................42
6.1.6.2.
Selection of method and time to evaluate, record and 
analyze the safety parameters........................................43
6.2.
Study Schedule................................................................................... 43
6.3.
Medication/device operation specification...................................... 44
6.3.1. Medication use...........................................................................44
6.3.2. Device operation specification..................................................46
6.4.
Study procedure ................................................................................ 46
6.4.1. Screening and Informed Consent ............................................46
6.4.2. Pre-Procedure/Baseline Assessments.......................................46
6.5.
Study Ablation Procedure Guidelines............................................. 48
6.5.1. Ablation Selections and parameters........................................48
6.5.2. Study Ablation Procedure Sequence & Guidelines................51
6.5.3. Collection of Ablation Procedure Data for Post-Analysis (non-
SOC) ...........................................................................................55
6.5.4. Data Collection during Study Ablation Procedure................55
6.5.5. Repeat Ablation Procedures.....................................................56
6.5.6. Post-Ablation Follow-up Schedule ..........................................57
6.6.
Monitoring plan................................................................................. 59
7.
Statistical Considerations......................................................................... 60

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7.1.
Statistical design, method and analysis procedure ........................ 60
7.2.
Calculation of sample size ................................................................ 61
7.2.1.
........................................................................61
7.2.2. Number of subjects with each disease in clinical trial and 
reason for determination ..........................................................61
7.2.3. Minimum and maximum number of subjects in each study site 
and justification.........................................................................62
7.2.4. Significance level and power of clinical trial ..........................62
7.2.5. Expected drop-out rate.............................................................62
7.3.
62
7.4.
Criteria for terminating the trial based on the statistical reasons 
and justification................................................................................. 62
7.5.
Statistical method of all data, together with the handling method 
of missing, unused and wrong data (including discontinuation and 
withdrawal) and unreasonable data................................................ 62
7.6.
Protocol deviation.............................................................................. 66
7.7.
Selection criteria for subjects included in the analysis and 
justification ........................................................................................ 66
7.7.1.
...................................................................66
7.7.2.
..........................................................................66
7.7.3.
..........................................................................66
7.7.4.
......................................................................66
8.
Data Management ..................................................................................... 66
9.
Feasibility Analysis.................................................................................... 67
9.1.
Possibility analysis on success .......................................................... 67
9.2.
Possibility analysis on failure........................................................... 67
10. Quality Control of Clinical Trial ............................................................. 67
11. Ethical Issues and Informed Consent of Clinical Trial......................... 68
11.1. Ethical considerations....................................................................... 68
11.2. Approval of trial protocol................................................................. 68
11.3. Informed consent process................................................................. 69
11.3.1. Informed consent process.........................................................69
12. Device Management.................................................................................. 69
12.1. Packaging and labeling of investigational devices ......................... 70
12.2. Shipment of investigational devices................................................. 70
12.3. Management of investigational devices........................................... 70
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12.4. Return and destruction of investigational devices......................... 71
13. AEs and Device Complaints reporting.................................................... 71
13.1. AEs recording.................................................................................... 71
13.2. Classification...................................................................................... 72
13.2.1. Primary Adverse Event.............................................................72
13.2.2. Serious AEs ................................................................................75
13.2.3. Non-Serious AEs........................................................................75
13.2.4. Anticipated AEs.........................................................................75
13.2.5. Unanticipated Serious Adverse Device Effects.......................75
13.2.6. Intensity or Severity, Outcome and Causality........................76
13.3. Device complaints.............................................................................. 77
13.4. Device deficiencies............................................................................. 77
13.5. Reporting procedures and contact information............................. 77
14. Provisions for Deviation from Clinical Trial Protocol and the 
Amendment to Clinical Trial Protocol.................................................... 78
15. Direct Access to Source Data and Documents........................................ 79
16. Finance and Insurance.............................................................................. 79
17. Contents of Clinical Trial Report............................................................ 79
18. Confidentiality Principle........................................................................... 80
19. Agreement on Publication of Trial Results............................................. 80
20. Responsibilities of Parties Involved......................................................... 81
20.1. Responsibilities of sponsor ............................................................... 81
20.2. Responsibilities of study sites and investigators............................. 81
20.3. Responsibilities of other interested parties..................................... 82
Investigator’s Statement:.................................................................................. 83
Appendix I: References..................................................................................... 84
Appendix II: Anticipated Adverse Events...................................................... 87

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List of Abbreviations
Abbreviation
Description on abbreviation
AAD 
Antiarrhythmic Drug 
ACC/AHA 
American College of Cardiology/American Heart Association 
ACE 
Asymptomatic Cerebral Emboli 
ACT 
Activated Clotting Time 
AE 
Adverse Event 
AEF 
Atrio Esophageal Fistula 
AF 
Atrial Fibrillation 
AFEQT 
Atrial Fibrillation Effect on Quality of Life 
AFL 
Atrial Flutter 
AT 
Atrial Tachycardia 
CA 
Competent Authority 
CABG 
Coronary Artery Bypass Graft 
CEC
Clinical Events Committee 
CHF 
Congestive Heart Failure 
COPD 
Chronic Obstructive Pulmonary Disease 
CPK 
Creatinine Phosphokinase 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
CS 
Coronary Sinus 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
CTI 
Cavotricuspid Isthmus 
CVA 
Cerebrovascular Accident or Stroke 
DM 
Diabetes Mellitus 
DMC 
Data Monitoring Committee 
EB 
Ethics Board 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EHRA AF 
European Heart Rhythm Association Atrial Fibrillation 
EMEA 
Europe, Middle East and Africa 
EP 
Electrophysiology 
ESC 
European Society of Cardiology 
FAM 
Fast Anatomical Mapping 
FDA 
Food and Drug Administration 

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Fr 
French 
FU 
Follow-Up 
MD-GCP 
Medical Device Good Clinical Practices 
GERD 
Gastroesophageal Reflux Disease 
GSMC 
Global Safety Monitoring Committee 
HM 
Holter Monitoring 
HRS/EHRA/ECAS 
Heart Rhythm Society / European Heart Rhythm Association / European 
Cardiac Arrhythmia Society 
ICE 
Intracardiac Echocardiography 
ICF 
Informed Consent Form 
IFU 
Instruction for Use 
ILR 
Implantable Loop Recorder 
IRE 
Irreversible Electroporation 
LA 
Left Atrium 
LBBB 
Left Bundle Branch Block 
LV 
Left Ventricle 
LVEF 
Left Ventricular Ejection Fraction 
MEDDEV 
Medical Device Directive Guidance 
MDD 
Medical Device Directive 
MDR 
Medical Device Regulation 
MI 
Myocardial Infarction 
MMSE 
Mini Mental State Examination 
MRA 
Magnetic Resonance Angiogram 
MRI 
Magnetic Resonance Imaging 
mRS 
Modified Rankin Scale 
NAE 
Neurological Assessment Evaluable 
NIHSS 
National Institute of Health Stroke Scale 
NYHA 
New York Heart Association 
PAF 
Paroxysmal Atrial Fibrillation 
PFA 
Pulsed Field Ablation 
PFE 
Pulsed Field Energy 
PI 
Principal Investigator 
PN 
Phrenic Nerve 
PNP 
Phrenic Nerve Paralysis 
PP 
Per Protocol 
PPI 
Proton Pump Inhibitors 
PSU 
Power Supply Unit 
PV 
Pulmonary Vein 
PVI 
Pulmonary Vein Isolation 

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QA 
Quality Assurance 
QC 
Quality Control 
QoL 
Quality of Life 
RA 
Right Atrium 
RF 
Radiofrequency 
RFCA 
Radiofrequency Catheter Ablation 
RV 
Right Ventricle 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SDV 
Source Data Verification 
SOC 
Standard Of Care 
SS 
Safety Analysis Set
SVC 
Superior Vena Cava 
TEE 
Transesophageal Echocardiography 
TIA 
Transient Ischemic Attack 
TS 
Transseptal 
TTE 
Transthoracic Echocardiography 
UM 
User Manual 

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goal. All subjects will be evaluated at discharge, 7 days, 1, 3, 6 and 12 months 
following the index procedure. One early success interim analysis is planned for 
this study. 
Sample size
A maximum of 147 subjects (123 evaluable non-roll-in subjects + max of 24 roll-
in subjects) will be enrolled. 
Study population
Patients aged 18 – 80 years with symptomatic drug refractory PAF and indicated 
for catheter ablation
Study duration
Duration: From 2022 to 2024
Description 
on 
study procedures
Study evaluation time points include:
1.
Screening 
2.
Study Procedure 
3.
Discharge 
4.
Follow-up at 7 days (telephone, virtual interview, or clinic visit)
5.
Follow-up at 1 month (telephone, virtual interview or clinic visit) 
6.
Follow-up at 3 months (clinic visit)
7.
Follow-up at 6 months (clinic visit) 
8.
Follow-up at 12 months (clinic visit)
Study objective
The primary objective of this study is to evaluate the long term off-AAD 
effectiveness of BWI IRE system in treatment of patients with symptomatic drug 
refractory PAF. Safety data will be evaluated as a secondary objective. 
Primary endpoint 

Long term effectiveness: Freedomb ≥30 seconds from documented 
asymptomatic and symptomatic AF, AT, and AFL of unknown origin+ based 
on electrocardiographic data (ECG or 24h Holter) during the effectiveness 
evaluation period (91-365 days post index procedure). Additionally, if a 
subject meets any one of the following criteria, then the subject will be 
considered an effectiveness failure:
a)
Failure to achieve acute procedural success. Acute procedural success is 
defined as confirmation of entrance block in clinically relevant PVs (all 
PVs except those that are silent and/or cannot be cannulated) after 
adenosine and/or isoproterenol challenge. 
b)
Greater (>) than 1 repeat ablations for AF, AT, and AFL of unknown 
origin in the blanking period or any repeat ablation or surgical treatment 
for AF, AT, and AFL of unknown origin during the effectiveness 
evaluation period.
c)
Non-study catheter failure, including:
i.
Use of a non-study catheter (NSC) to treat pulmonary vein targets 
to achieve isolation of clinically relevant PVs (all PVs except those 
that are silent and/or cannot be canulated) and/or to ablate left atrial 
non-PV AF targets during the index procedure
ii.
Use of a non-study catheter to treat pulmonary vein targets to 
achieve isolation of clinically relevant PVs (all PVs except those 
that are silent and/or cannot be canulated) during repeat procedure 
in the blanking period.

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d)
Direct current or pharmacological cardioversion for AF, AT, and AFL of 
unknown origin during the effectiveness evaluation period.
e)
Continuous AF, AT, and AFL of unknown origin on a standard 12-lead 
ECG during the effectiveness evaluation period.
f)
A Class I and/or Class III AAD is prescribed for AF, AT, and AFL of 
unknown origin during effectiveness evaluation period, or end date of 
Class I and/or Class III AAD past day 90 post procedure.
g)
Oral amiodarone is prescribed post index ablation procedure.
+AFL of unknown origin is defined as all AFL except those CTI dependent AFL as 
confirmed by 12-Lead electrocardiogram (ECG) or entrainment maneuvers in an 
EP study
Secondary 
endpoints 

Procedure and device safety: The incidence of Primary Adverse Events 
(AEs) (within seven (7) days of the ablation procedure which uses 
investigational devices per protocol, including the initial and repeat 
procedures). PAEs include the following Adverse Events (Aes): Atrio-
Esophageal 
Fistula*, 
Cardiac 
Tamponade**,***/ 
perforation**, 
PNP 
(permanent)+, Pulmonary Vein Stenosis++, Device or procedure related 
death+++, Stroke/ CVA†,††, Major Vascular Access Complication Bleeding, 
Thromboembolism, Myocardial Infarction, TIA, Pericarditis, Pulmonary 
Edema (Respiratory insufficiency), Heart Block, Vagal Nerve Injury/ 
Gastroparesis
* Atrio-esophageal fistula occurring up to 90 days post AF ablation process 
procedure will be considered a PAE.
**Cardiac Tamponade/Perforation occurring up to 30 days post AF ablation 
process procedure will be considered a PAE
*** Hemodynamic compromise or instability is defined as Systolic BP < 80 
mm Hg.
+ Absent phrenic nerve function as assessed by a sniff test. Refer to Table 4 
for permanent phrenic nerve paralysis definition.
++ Pulmonary Vein Stenosis occurring anytime during the 12-month follow 
up period will be considered a PAE.
+++ Device or procedure-related death anytime during or after the ablation 
procedure
† Non-focal global encephalopathy requires unequivocal evidence based 
upon neuroimaging studies to be reported as a stroke
†† Modified Rankin score assessments should be made by certified 
individuals.

Occurrence of Serious Adverse Events (SAEs) within 7 days (early-onset), 
8-30 days (peri-procedural) and >30 days (late onset) of initial ablation 
procedure

Acute Procedural Success defined as confirmation of entrance block in all 
clinically relevant targeted PVs after adenosine/ isoproterenol challenge. 
Touching up with focal catheter will be considered as acute procedural 
failure.

Acute reconnection identified by adenosine/isoproterenol challenge. 
Among all clinically relevant targeted PVs and by subject

Rate of repeat ablation within the 12M FU period, including timing 
(blanking period or after blanking) and rate of PV reconnection

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
Procedural data, including but not limited to

Total procedure time

Mapping time

PFA application time

Number of PFA applications by PV and by subject

Total fluoroscopy time

Study catheter dwell time

Ablation settings used

Use of paralytics and anesthesia
Inclusion criteria
1.
Diagnosed with Symptomatic PAF (Physician’s note indicating recurrent 
self-terminating AF). At least one (1) electrocardiographically documented 
AF 
episode 
within 
twelve 
(12) 
months 
prior 
to 
enrollment. 
Electrocardiographic documentation may include, but is not limited to, 
electrocardiogram (ECG), Holter monitor, or other electrocardiographical 
devices accepted by investigators.
2.
Failed at least one (1) Class I or Class III AAD as evidenced by recurrent 
symptomatic AF, contraindication or intolerable to both Class I and Class III
AAD.
3.
Age 18 - 80 years.
4.
Able and willing to comply with all pre-procedure, post-procedure, and 
follow-up testing and visit requirements.
5.
Willing and capable of providing consent.
Exclusion criteria
1.
AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-
cardiac cause (e.g., untreated documented obstructive sleep apnea and acute 
alcohol toxicity). 
2.
Previous LA ablation or surgery 
3.
Patients known to require ablation outside the PV region (atrioventricular 
reentrant tachycardia, atrioventricular nodal reentry tachycardia, atrial 
tachycardia, atrial flutter of unknown origin, ventricular tachycardia and 
Wolff-Parkinson-White).
4.
Previously diagnosed with persistent AF (> 7 days in duration)
5.
Severe dilatation of the LA (documented LAD >50mm antero-posterior 
diameter by Transthoracic Echocardiography (TTE) within 6 month prior to
enrollment)
6.
Documented left atrium (LA) thrombus within 48 hours prior to the index 
procedure by TEE or CT (in case of intolerance to TEE), or by ICE prior to 
transeptal puncture during procedure.
7.
Documented severely compromised LVEF (LVEF <40%) by imaging within 
6 months prior to enrollment
8.
Uncontrolled heart failure or New York Heart Association (NYHA) Class III 
or IV
9.
History of blood clotting, bleeding abnormalities or contraindication to 
anticoagulation (heparin, warfarin, or dabigatran)
10. History of a documented thromboembolic event (including TIA) within the 
past 12 months, or history of a documented left atrial appendage (LAA) 
thrombus
11. History of a documented symptomatic lacunar infarction within the past 12 
months
12. Previous PCI/MI within the past 2 months
13. Coronary Artery Bypass Grafting (CABG) surgery within past 6 months

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1.
Sponsor Information
(I).
Name of sponsor
Biosense Webster, Inc. (BWI)
(II).
Address of sponsor
31 Technology Drive, Suite 200 Irvine, CA 92618
(III). Contact information of sponsor
+1 800-729-9010
(IV). Name, address, contact information
Johnson & Johnson Medical (Shanghai) Ltd. (JJMS)
Location C, 1/2/3 F, #439 Fu Te Xi Yi Road, Pilot Free Trade Zone, Shanghai, 
P.R.China
Email: china_ct_safety@its.jnj.com
Tel.: 021-33378888
Address: Building A, Xinyan Tower, No.65 Guijing Road, Xuhui District, 
Shanghai
2.
Clinical Trial Objective and Contents
2.1.
Clinical trial objective
The primary objective of this study is to evaluate the long term off-AAD 
effectiveness of BWI IRE system in treatment of patients with symptomatic drug 
refractory PAF. Safety data will be evaluated as a secondary objective. 
2.2.
Clinical trial contents
This study is a prospective, multicenter, single-arm design with a performance 
goal. All subjects will be evaluated at discharge, 7 days, 1, 3, 6 and 12 months 
following the index procedure. One early success interim analysis is planned for 
this study. Study population are patients aged 18 – 80 years with symptomatic
drug refractory PAF and indicated for catheter ablation.
A total of 123 non-roll-in subjects will be enrolled. Given at most 2 roll-in cases 
are planned for each investigator, a maximum of 147 subjects (including 123 non-
roll-in and maximum of 24 roll-in subjects) will be enrolled in this study. All 
patients are treated with BWI IRE system and then followed for 12 months.

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The primary endpoint is long term effectiveness without AAD use in effectiveness 
evaluation period, defined as freedom
≥30 seconds
from documented 
asymptomatic and symptomatic AF, AT, and AFL of unknown origin based on 
electrocardiographic data (ECG or 24h Holter) during the effectiveness evaluation 
period (91-365 days post index procedure), with additional failure modes in 
section 6.1.5
Safety endpoint is defined as the incidence of Primary Adverse Events (Aes) 
(within seven (7) days of the ablation procedure which uses investigational 
devices per protocol, including the initial and repeat procedures). PAEs include 
the following Adverse Events (Aes): Atrio-Esophageal Fistula, Cardiac 
Tamponade/ perforation, PNP (permanent), Pulmonary Vein Stenosis, Device or 
procedure related death, Stroke/ CVA, Major Vascular Access Complication 
Bleeding, Thromboembolism, Myocardial Infarction, TIA, Pericarditis, 
Pulmonary Edema (Respiratory insufficiency), Heart Block, Vagal Nerve Injury/ 
Gastroparesis. More details can be found in section 6.1.6
3.
Background Information of the Clinical Trial
3.1.
Disease introduction
3.1.1. Explanation of the disease
Atrial Fibrillation (AF) is the most common sustained arrhythmia in humans. It 
affects anywhere from 0.4% to 1% of the general population, and increases in 
prevalence with age to approximately 8% in patients over 80 years of age.1, 2 The 
primary clinical benefit of AF ablation is improvement in Quality of Life (QoL) 
resulting from the elimination of arrhythmia-related symptoms such as 
palpitations, fatigue, or effort intolerance.3 In recognition of this, the elimination 
of symptomatic atrial arrhythmias was recommended by the 2017 
HRS/EHRA/ECAS Consensus on Catheter and Surgical Ablation of Atrial 
Fibrillation.3 The opinion of the ESC as expressed in their 2019 AF Management 
Guidelines is that “Catheter ablation of symptomatic Paroxysmal Atrial 
Fibrillation (PAF) is recommended to improve AF symptoms in patients who have 
symptomatic recurrences of AF on Antiarrhythmic Drug (AAD) therapy and who 
prefer further rhythm control therapy, when performed by an electrophysiologist 
who has received appropriate training and is performing the procedure in an 
experienced center.”2, 4, 5
3.1.2. Selection of diagnosis and treatment method
The 2017 HRS/EHRA/ECAS consensus statement states that electrical isolation 
of the Pulmonary Veins (PVs) from the Left Atrium (LA) is the “cornerstone for 
most AF ablation procedures” and that “complete electrical isolation of all PVs 

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should be the goal.”3 Point-by-point ablation with radiofrequency (RF) catheters 
has provided positive results for treating many types of supraventricular 
arrhythmias,6, 7 including PAF.6-12 However, the procedure is technically complex 
and has a long learning curve. RF ablation success is highly dependent on operator 
skill and is associated with a high degree of PV reconnection.13-15 Additionally, 
RF ablation carries a major complication rate of roughly 4.5%.16
In order to reduce technical complexity and potentially decrease major 
complications, circular ablation catheters were developed. Use of a Circular IRE 
Catheter allows for a different energy source for ablation and selective tissue 
destruction utilizing PFA energy17-25 to create lesions and isolate PVs.
While RF and cryo-ablation techniques are based on thermal energy transfer to 
induce local tissue necrosis, Irreversible Electroporation (IRE) is a non-thermal 
cell death following pulsed field ablation technology which might be used to treat 
atrial arrhythmias.23 It is suggested that non-thermal IRE is the trigger of apoptotic 
processes at the cellular level because the major damages occur after 
electroporation, within minutes/hours after the pulse application.26-28 Short pulses 
with high voltages cause unrecoverable permeabilization of cell membranes, 
triggering apoptosis rather than necrosis, and as such might be safer for structures 
adjacent to the myocardium.25
It has been known that uniphasic electric pulses cause muscle contractions, using 
biphasic pulses, should prevent muscle contractions during IRE. It is believed that 
using a biphasic waveform will mitigate muscle contractions during IRE and 
therefore gives the possibility to perform procedures without administration of 
paralytic agents.
High correlation has been observed in animal models between targeted areas and 
tissue death with well distinguishable transition zones between treated and 
untreated tissue.17
IRE is considered nonthermal if the optimal balance has been reached to induce 
nonnecrotic selective cellular death. The technique has the capability to spare 
adjacent heat sensitive structures or tissues which would be of benefit in the 
reduction of possible complications know with RF and cryo energy. Although 
using the same electrical parameter, IRE energy delivery may be affected by other 
parameters like active electrode area impacting the tissue-electrode impedance. 
Therefore, literature describes the need of balancing Pulsed Field Ablation (PFA) 
application parameters (in example voltage, pulse width and interpulse distance) 
with physical parameters (in example electrode area, reference proximity) to 
achieve optimal efficacy and possible benefits of this approach versus RF energy 
delivery techniques.24

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IRE of the myocardium is studied on animals resulting in clear lesions in the 
cardiac tissue, with no charring or temperature changes. Lesion size correlations 
are described in literature with pulse duration, number of pulses, higher voltage 
and lower interpulse distance. Interestingly the majority of the animal studies 
report sparing of the extracellular structures. 29-35
Influence on adjacent structures has been previously studied. Of the well 
described complications in RF ablation techniques, the tissue specificity of IRE 
has been considered as a major advantage.36 Recoverable proof of IRE effect on 
phrenic nerves has been described, suggesting that permanent damage can be 
avoided with IRE.37-40 As rare but dangerous complication of RF ablation, namely 
development of lethal Atrio-Esophageal Fistula (AEF), might be minimized with 
IRE as it’s suggestive that the risk with IRE would only be limited to the muscular 
layer of the esophagus. 41
Biosense Webster developed the novel proprietary technology system, including 
Multi-Channel Circular IRE Catheter and Multi-Channel IRE Generator. With 
standardized bipolar, biphasic, non-thermal IRE energy delivery and circular 
catheter design, BWI IRE system might be confirmed to provide expected long 
term efficacy and safety performance in this study. 
3.2.
Previous Experience with Biosense Webster IRE Ablation System
Pre-clinical studies were conducted to assess the safety and effectiveness of the 
IRE ablation system. One clinical study is ongoing in Europe.
3.2.1. Animal Testing: Porcine Beating Heart Model (GLP Survival Study)
An in-vivo animal study titled “Safety Evaluation of the Circular IRE Catheter 
and IRE Generator in a Chronic Porcine Beating Heart Model” Testing performed 
under this protocol was GLP compliant and conformed to the guidelines for 
nonclinical laboratory studies as described in the Code of Federal Regulations, 21 
Part 58.
Purpose
The purpose of this study was to demonstrate the overall safety of the Biosense 
Webster IRE Ablation System, which includes the IRE Generator and Circular 
IRE Catheter, when ablating at clinically relevant anatomical locations like the 
pulmonary veins and left posterior wall, in a simulated clinical use scenario in 
combination with a CARTOTM 3 System, nGEN irrigation pump, catheter 
interface cables, and a pacing system in a chronic beating heart model. Various 
doses (differing in the number of applications) of PFA were delivered to 
characterize performance and safety relative to a radiofrequency (RF) control, 
THERMOCOOL SMARTTOUCH®
SF Catheter with SMARTABLATE®

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Generator. As part of this study, BWI captured and analyzed ECG data to 
determine whether arrythmia (if any) is correlated with timing of pulse delivery 
with respect to the cardiac cycle. Additionally, overall performance of the BWI 
IRE Ablation System will be evaluated using a 7-point Likert Scale
Scope
The study consisted of four arms, 3 PFA and 1 RF. All PFA animals were treated 
with the same energy setting with different numbers of PFA applications (doses) 
at each catheter location, without moving the catheter: Low Dose (1 
application/catheter location), Nominal Dose (3 applications/catheter location), 
and High Dose (6 applications/catheter location). In each of these PFA arms, the 
designated dose (low, nominal or high) is delivered at four locations per 
pulmonary vein (i.e., 3 x 4 pattern) and the same dose is employed in every animal 
in each of the three PFA arms. Additionally, an RF arm served as a comparative 
control. A total of 12 animals (plus 2 backups) were included in the study. Note 
that in this discussion, and throughout the study report, the terms ablation and 
application are used synonymously to represent a user initiated PFA energy 
delivery event while the term dose or dosage are used to represent the number of 
applications delivered before the catheter is moved.
Safety of the Test devices were evaluated using the following assessments:
•
Occurrence of thrombus and/or char on the catheter tip, following 
energy delivery
•
Occurrence of clinically significant steam pop (leading to significant 
pericardial effusion and/or cardiac tamponade)
•
Occurrence of mural thrombus in the treated heart chambers
•
Occurrence of pulmonary vein (PV) stenosis
•
Occurrence of collateral damage to organs surrounding organs (lungs, 
esophagus, phrenic nerve, pericardium)
•
Occurrence of intracardiac tissue damage due to mechanical injury 
from the device

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•
Occurrence of thrombo-emboli (micro-emboli) in
upstream/downstream tissues
Efficacy of the Test devices were evaluated using the following assessments:
•
Ability to demonstrate 100% acute effectiveness of ablation in the left 
atrium
•
Ability to demonstrate 80% chronic effectiveness of ablation at the 
PVs
Performance of the Test devices were evaluated using the following assessments:
•
Survey answers and qualitative results in the form of written 
comments will be recorded and analyzed. The results will be 
considered passing if average of all the responses per question meet 5 
and above on the Likert’s scale of 1-7
In addition to these safety and effectiveness endpoints, the study also included: 
•
Detailed gross and histological assessment
•
An arrhythmogenicity evaluation was performed which annotated 
each application of energy to identify where in the cardiac cycle 
energy was delivered
Result Summary
Testing was performed on twelve (12) male Yorkshire pigs. All animals in the 
arms 1-3 were treated using PFA with the IRE Generator and Circular IRE
Catheter. Doses used were Low (arm 1), Nominal (arm 2), and High (arm 3). As 
a control, animals in Group 4 received a clinically relevant RF dose using the 
SMARTABLATE Generator and THERMOCOOL SMARTTOUCH SF Catheter 
and served as the control group. After concluding Day 30±5 follow-up procedures, 
animals were humanely euthanized under anesthesia, and gross necropsies were 
performed.
Energy was applied to targeted tissue areas wall thickness and their anatomic 
relevance to an atrial fibrillation treatment procedure. These included areas in the 
left atrium (LA) such as the right superior pulmonary vein (RSPV) and right 
inferior pulmonary vein (RIPV), atrial roof/posterior wall, left atrial appendage, 
and mitral valve annulus, and in the right atrium (RA) the lateral wall.
Safety:
Throughout the procedure, no signs of respiratory distress, pain or other abnormal 
behaviors were observed in any of the study animals. Additionally, no mural 

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thrombus, coagulum or charring, cardiac effusion and/or tamponade were noted 
for the duration of the study nor was evidence of steam pop detected in any of the 
enrolled animals. All animals survived until their scheduled termination time 
points.
In all PFA arms, ablation energy was applied directly to the phrenic nerve. In the 
RF arm, RF was applied more conservatively adjacent to the phrenic so as not to 
risk the chronic survival of the animal. Subsequent phrenic nerve capture after 
pacing was successful in all animals in all arms, demonstrating no loss of phrenic 
function. Pulmonary vein stenosis assessment was based on fluoroscopic 
measurements. No clinically relevant reduction in PV diameter was noted for any 
animal following Day 1 ablations and Day 30±5 follow-up (remap) procedures. 
Upon gross pathological inspection, it was noted that ablations were created in 
intended anatomical regions with no significant collateral injury.
All animals in all arms (test and control) showed a similar safety profile for the 
specified protocol endpoints.
All safety acceptance criteria for the study were met.
Efficacy:
Three physicians performed the ablation treatment on each of 1 animal per arm.
Confirmation of elimination of PV potential using a Pentaray® diagnostic 
mapping catheter, following initial ablation procedure was confirmed in all 
animals, meeting the expectation of 100% acute effectiveness of ablation in the 
left atrium.
For chronic evaluations on Day 30±5, all PFA treated animals presented 100% 
chronic PV isolation, although some areas of low voltage can be seen more 
prominently in the “Low” arm compared to the Nominal and High. In the RF arm, 
83.3% chronic PV isolation was achieved.
All effectiveness acceptance criteria for the study were met.
Performance:
The overall performance of the Circular IRE Catheter and IRE Generator was 
evaluated using a 7-point Likert Scale by three (3) physicians. The average of all 
the responses per question met a 5 and above on the Likert’s scale, meeting the 
acceptance criteria. All performance acceptance criteria for the study were met.
Gross Pathology and Histology Analysis:
Gross Pathology

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There were no gross signs of collateral injury to any of the adjacent anatomic 
structures, including aorta, lungs, esophagus, pericardium, and/or phrenic nerve 
adjacent to the ablation lesions.
Histology
All histology findings were within expectations. Both PFA and RF treated tissues 
produced expected degree of post-ablation tissue modulation and repair, but the 
RF treatment group differed remarkably when the severity of the lesions was 
compared.
Conclusion
The Circular IRE Catheter with the IRE Generator meets all acceptance criteria 
as listed in protocol P/TR-0034530.
This study confirms the overall effectiveness and safety of the Circular IRE 
Catheter when used with the IRE Generator and the CARTOTM 3 System, when 
simulating a clinical pulmonary vein isolation (PVI) procedure in a porcine 
beating heart model.
3.2.2. Summary of OUS Clinical Study
BWI has initiated a prospective, single-arm, multi-center, pre-market clinical 
evaluation of the IRE Ablation System in Europe (InspIRE, NCT04524364) to 
demonstrate the safety and long-term effectiveness in the treatment of paroxysmal 
atrial fibrillation when compared to a performance goal. Enrollment commenced 
on August 26, 2020, and the study will enroll up to 180-330 subjects with sample 
size adaptation based on accruing data. The study is currently ongoing.
The study has 2 sequential phases. Wave 1, the safety characterization phase of 
the study enrolled 40 subjects. Wave 2, the pivotal phase of the study is currently 
enrolling.
Acute procedural success, defined as confirmation of entrance block in all 
clinically relevant targeted pulmonary veins after adenosine/ isoproterenol 
challenge without use of a non-study catheter to achieve PVI, was achieved in all 
subjects treated with the study catheter in Wave 1 of the study.
No primary adverse events including atrio-esophageal fistula, phrenic nerve 
paralysis, cardiac tamponade/perforation, pulmonary vein stenosis, device or 
procedure-related death, or stroke/CVA have been reported in the Wave 1 phase 
of the study.

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4.3.
Study population
Patients aged 18 – 80 years with symptomatic drug refractory PAF and indicated 
for catheter ablation.
5.
Indications, Contraindications and Precautions of the Product (From 
IFU approved by country of origin)
Please refer to IFUs of Multi-Channel IRE Generator（D-1417-01-I）and Circular 
IRE Catheter（D-1412-01-SI）
6.
Overall Design
6.1.
Study design
6.1.1. Study objective
The primary objective of this study is to evaluate the long term off-AAD 
effectiveness of BWI IRE system in treatment of patients with symptomatic drug 
refractory PAF. Safety data will be evaluated as a secondary objective. 
6.1.2. Selection of study method and justification
This study is a prospective, multicenter, single-arm design with a performance 
goal. Its rationale is as follows:
Prospective: The prospective study is insusceptible to bias, with no need of recall, 
in which the incidence can be calculated, and the definition of symptom and
condition can maintain consistency.
Multicenter: With patients from multiple sites more representative than that from 
a single site, the result bias caused by systematic errors of a single site may be 
reduced.
CCI

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Single arm with a performance goal: The Sponsor has carefully considered the 
most appropriate study design for the assessment of the IRE Ablation system. The 
2017 HRS/EHRA/ ECAS/APHRS/SOLAECE Expert Consensus3 Statement on 
Catheter and Surgical Ablation of Atrial Fibrillation addressed the appropriateness 
and concerns of randomized control (non-inferiority) studies–- “…the possibility 
of a downward “creep” in acceptable effectiveness (if each device is numerically 
inferior but statistically equivalent to the prior comparator device). In the future, 
we expect that devices designed to treat patients with symptomatic PAF might 
alternatively be evaluated in nonrandomized trials, comparing prespecified 
performance goals or objective performance criteria (OPC), if uniformly 
established and applied.” Similar concerns may be extended to the evaluation of 
safety given the rapid pace of technology development in this arena. This is 
balanced by the establishment of the treatment of PAF by catheter ablation as a 
safe procedure with pulmonary vein isolation (PVI) as the cornerstone of 
treatment. Data published from many recent prospective multi-center clinical 
trials43-46 for ablation devices demonstrate that the safety and effectiveness rates 
for similar primary endpoints are comparable across the varied technologies in a 
well-defined PAF patient population, further supporting acute PVI as a reliable 
treatment in reducing long term recurrence of PAF. Accordingly, this study is 
designed to be multicenter and single arm with comparison to rigorously 
determined performance goals for effectiveness. The planned performance goal 
for long term effectiveness is 50%, based on the minimum chronic acceptable 
success rate for paroxysmal AF at 12-month follow-up as recommended in the 
2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement3 on 
Catheter and Surgical Ablation of AF.
Meanwhile, in the trial, the appropriate sample size as needed will be estimated 
according to the scientific hypothesis of comparison between the trial group and 
the performance goal, and the permissible Type I and Type II errors, ensuring the 
statistical significance of the results.
6.1.3. Measures for reducing and avoiding bias
Prospective design will be adopted for this study, so as to avoid bias that may be 
caused by retrospective study.
Strict inclusion and exclusion criteria will be implemented to avoid selection bias. 
Meanwhile, in the study, the data of objective indicators will be collected. The 
study related data will be recorded in the original medical records as much as 
possible, and checked in the monitoring process. The training for the investigators 
should be enhanced, so as to assure the scientific attitude of investigators.
Investigators should communicate more with subjects to improve their 

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compliance. This will help to reduce the informational bias.
Clinical outcomes will be measured in a standardized manners using standard 12
or 15 leads ECG and 24h Holter, which are standardized and objective clinical 
assessment tools for identify the recurrence of atrial arrthymia.
6.1.4. Selection of subjects
6.1.4.1.
Inclusion criteria
1.
Diagnosed with Symptomatic PAF (Physician’s note indicating recurrent 
self-terminating AF). At least one (1) electrocardiographically 
documented AF episode within twelve (12) months prior to enrollment. 
Electrocardiographic documentation may include, but is not limited to, 
electrocardiogram (ECG), Holter monitor, or telemetry strip.
2.
Failed at least one (1) Class I or Class III AAD as evidenced by recurrent 
symptomatic AF, contraindicated or intolerable to both Class I and Class 
III AAD.
3.
Age 18 - 80 years.
4.
Able and willing to comply with all pre-procedure, post-procedure, and 
follow-up testing and visit requirements.
5.
Willing and capable of providing consent.
6.1.4.2.
Exclusion criteria
1.
AF secondary to electrolyte imbalance, thyroid disease, or reversible or 
non-cardiac cause (e.g., untreated documented obstructive sleep apnea 
and acute alcohol toxicity).
2.
Previous LA ablation or surgery 
3.
Patients known to require ablation outside the PV region (atrioventricular 
reentrant tachycardia, atrioventricular nodal reentry tachycardia, atrial 
tachycardia, atrial flutter of unknown origin, ventricular tachycardia and 
Wolff-Parkinson-White).
4.
Previously diagnosed with persistent AF (> 7 days in duration)
5.
Severe dilatation of the LA (documented LAD >50mm antero-posterior 
diameter by Transthoracic Echocardiography (TTE) within 6 month prior 
to enrollment)
6.
Documented left atrium (LA) thrombus within 48 hours prior to the index 
procedure by TEE or CT (in case of intolerance to TEE) , or by ICE prior 

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to transeptal puncture during procedure
7.
Documented severely compromised LVEF (LVEF <40%) by imaging 
within 6 months prior to enrollment
8.
Uncontrolled heart failure or New York Heart Association (NYHA) Class 
III or IV
9.
History of blood clotting, bleeding abnormalities or contraindication to 
anticoagulation (heparin, warfarin, or dabigatran)
10. History of a documented thromboembolic event (including TIA) within 
the past 12 months, or history of a documented left atrial appendage 
(LAA) thrombus
11. History of a documented symptomatic lacunar infarction within the past 
12 months
12. Previous PCI/MI within the past 2 months
13. Coronary Artery Bypass Grafting (CABG) surgery within past 6 months
14. Valvular surgery, cardiac surgery (e.g. ventriculotomy, atriotomy) or 
valvular cardiac (surgical or percutaneous) procedure. 
15. Unstable angina pectoris within the past 6 months 
16. Anticipated cardiac transplantation, cardiac surgery or other major 
surgery within the next 12 months. 
17. Significant pulmonary disease (e.g., restrictive pulmonary disease, 
constrictive or chronic obstructive pulmonary disease) or any other 
disease or malfunction of the lungs or respiratory system that produces 
severe chronic symptoms 
18. Known significant PV anomaly that in the opinion of the investigator 
would preclude enrollment in this study 
19. Has known pulmonary vein stenosis 
20. Pre-existing hemi diaphragmatic paralysis
21. Acute illness, active systemic infection or sepsis 
22. Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or 
patch or other abnormality that precludes catheter introduction or 
manipulation. 
23. Severe mitral regurgitation (Regurgitant volume 60 mL/beat, Regurgitant 
fraction 50%, and/or Effective regurgitant orifice area 0.40cm2)

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24. Presence of implanted pacemaker or Implantable Cardioverter-
Defibrillator (ICD) or other implanted metal cardiac device that may 
interfere with the IRE energy field. 
25. Presence of a condition that precludes vascular access (such as IVC filter) 
26. Significant congenital anomaly or a medical problem that in the opinion 
of the investigator would preclude enrollment in this study 
27. Categorized as vulnerable population and requires special treatment with 
respect to safeguards of well-being 
28. Current enrollment in an investigational study evaluating another device 
or drug. 
29. Women who are pregnant (as evidenced by pregnancy test if pre-
menopausal), lactating, or who are of childbearing age and plan on 
becoming pregnant during the course of the clinical investigation. 
30. Life expectancy less than 12 months.
31. History of massive haemorrhage within the past 6 months.
32. Blood test anomaly: HGB≤90 g/L or PLT <100*109 /L.
33. Liver function anomaly: Cirrhosis or bilirubin > 2 times the upper limit 
of the normal value or transaminase anomaly: AST/ALT/ALP > 3 times 
the upper limit of the normal value.
34. Renal function anomaly: Dialysis, kidney transplant, Cr > 2.26 mg/d or > 
200 µmol/L, CCR < 30 mL/ (min*1.73 m2).
35. Presenting contra-indications for the devices used in the study, as 
indicated in the respective Instructions for Use (IFU)
6.1.4.3.
Reasons for early termination of subjects
Possible reasons for early termination may include, but are not limited to the 
following:
1.
Withdrawal of informed consent form (ICF): The subject decides to 
withdraw from the study. This decision must be“" independent decision“" 
and should be documented in the subject study file;
2.
Investigato’'s discretion: The investigator may choose to the withdraw a 
subject from the study if there are safety concerns;
3.
Adverse events (aEs): AE or SAE may lead to subject discontinuation
from the study. If the investigator decides to discontinue a subject from 

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the study, this subject must be followed up until the AE is resolved or 
until the stable clinical endpoint is reached;
4.
Death (if applicable);
5.
Loss to follow-up: All subjects should return to participate in all 
scheduled clinical follow-ups, providing the appropriate contact 
information in order to complete the specified (telephone) follow-up.
Every attempt will be made to have all subjects complete the follow-up 
visit schedule. A subject will not be considered lost to follow-up until the 
last study visit. If a subject can’t return for mandatory clinical visits, 3 
telephone calls should be made to attempt to contact the subject to return 
to clinics and/or obtain safety information. Each attempt to contact 
should be recorded in the source document. If the subject does not
response to 3 telephone calls, the investigator must send a registered mail 
or the EMS which can record the mode of sending and receiving to the 
subject. If the subject makes no response to the registered mail or EMS 
which can record the mode of sending and receiving and makes no further 
contact, this subject should be considered to have missed the scheduled 
visit. 
6.
Termination by the sponsor.
Procedure for subject’s termination in the study:
If the subject is terminated from the study before end of visit in the study, the 
reasons for discontinuation should be documented in the source document and 
kept in the study files and submitted via CRF/eCRF.
Subjects with premature discontinuation from the study will be included in the 
analysis set according to the definition of analysis set in the protocol; however, 
new subjects may not be enrolled to replace these subjects.  
Criteria for sponsor’s termination of the trial are as follows:
The sponsor reserves the right to temporarily suspend/terminate or prematurely 
discontinue the studies either at a single site, multiple sites or all sites. Reasons 
may include, but are not limited to safety issue, ethical issue, administrative issue, 
inaccurate or incomplete data record, non-compliance or
unsatisfactory 
enrollment with respect to quality or quantity.
Procedure for sponsor’s termination of the study:
If the study is prematurely terminated or suspended, the sponsor will inform all 
institutions of the termination or suspension and the reason(s) for the termination 
or suspension, in accordance with applicable regulatory requirement(s). The 

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investigators and EC should also be informed and provided with reason(s) for the 
termination or suspension by the institutions, as specified by the applicable 
regulatory requirement(s). The suspended study should not be resumed without 
the consent of the EC.
6.1.4.4.
Enrollment time
Subjects will be considered successfully enrolled into the study after completion
of the following process:
• Completion of the informed consent process and signing the ICF.
• Discretion by the investigator that the subject meets all inclusion criteria
(including intra-procedure inclusion criteria) and does not meet any 
exclusion criteria.
No operation procedures related to the study (except for SOC) should be 
conducted prior to signing the ICF.
6.1.4.5.
Expected overall duration of clinical trial and justification
The expected overall duration is about 31 months, including the time of EC, 
signing the contract, subject’' enrollment and follow-up, data management and 
statistical analysis, and writing the clinical summary report.
6.1.4.6.
Expected duration of participation of each subject
The duration of each subject’s participation in the study is about 12 months
according to the follow-up schedule specified in the protocol.
6.1.4.7.
Number of subjects required for the clinical trial
A total of 123 non-roll-in subjects will be enrolled. Given at most 2 roll-in cases 
are planned per each investigator, a maximum number of 147 subjects (including 
both non-roll-in and roll-in subjects) will be enrolled.
See Section 7.2 “Calculation of Sample Size” for the basis for selecting such 
sample size.
6.1.4.8.
Subject Enrollment Disposition
Enrolled Subjects: Patients who sign the ICF and meet all eligibility criteria.
Excluded Subjects: Subjects who are enrolled but never undergo insertion of 
the study catheter. Excluded subjects will be subjected to safety event 
reporting between ICF signature and date of exclusion. Enrolled Subjects 
found to be ineligible prior to insertion of the catheter are also considered as 
excluded.

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Evaluable Subjects: All enrolled subjects who have the study catheter inserted.
Discontinued Subjects: Evaluable subjects but do not undergo ablation (i.e., 
no energy is delivered with the study catheter).
o
Discontinued subjects will remain in follow-up for 3-months post catheter 
insertion. 
o
If an SAE is reported for a discontinued subject, the subject will be 
followed until event resolution (with or without sequelae), stabilization, 
or until the event is adequately explained. 
Lost to Follow-up Subjects: Evaluable subjects of which contact is lost after 
most recent visit (despite 3 documented attempts to contact the subject). 
Withdrawn / Early Termination Subjects: Subjects who withdraw consent for 
study participation or are withdrawn by the investigator, are terminated from 
the study prior to completion of all follow-up visits. 
Completed Subjects: Enrolled subjects who have not been excluded, 
discontinued, withdrawn, terminated early, or lost-to-follow-up from the study 
prior to the final study visit. 
6.1.5. Effectiveness evaluation method
6.1.5.1.
Description on effectiveness parameters
1) Primary effectiveness endpoint:
Long term effectiveness: Freedom ≥30 seconds from documented 
asymptomatic and symptomatic AF, AT, and AFL of unknown origin+
based on electrocardiographic data (ECG or 24h Holter) during the 
effectiveness evaluation period (91-365 days post index procedure). 
Additionally, if a subject meets any one of the following criteria, then the 
subject will be considered an effectiveness failure:
a) Failure to achieve acute procedural success. Acute procedural 
success is defined as confirmation of entrance block in clinically 
relevant PVs (all PVs except those that are silent and/or cannot be 
cannulated) after adenosine and/or isoproterenol challenge. 
b) Greater (>) than 1 repeat ablations for AF, AT, and AFL of 
unknown origin in the blanking period or any repeat ablation or 
surgical treatment for AF, AT, and AFL of unknown origin during 
the effectiveness evaluation period.
c) Non-study catheter failure, including:

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
Use of a non-study catheter (NSC) to treat pulmonary 
vein targets to achieve isolation of clinically relevant 
PVs (all PVs except those that are silent and/or cannot 
be canulated) and/or to ablate left atrial non-PV AF 
targets during the index procedure

Use of a non-study catheter to treat pulmonary vein 
targets to achieve isolation of clinically relevant PVs 
(all PVs except those that are silent and/or cannot be 
canulated) during repeat procedure in the blanking 
period
d) Direct current or pharmacological cardioversion for AF, AT, and 
AFL of unknown origin during the effectiveness evaluation period.
e) Continuous AF, AT, and AFL of unknown origin on a standard 12
or 15-lead ECG during the effectiveness evaluation period.
f) A Class I and/or Class III AAD is prescribed for AF, AT, and AFL 
of unknown origin during effectiveness evaluation period, or end 
date of Class I and/or Class III AAD past day 90 post procedure.
g) Oral amiodarone is prescribed post index ablation procedure
+AFL of unknown origin is defined as all AFL except those CTI dependent AFL 
as confirmed by 12 or 15-Lead electrocardiogram (ECG) or entrainment 
maneuvers in an EP study
2) Secondary effectiveness endpoint:
Acute Procedural Success defined as confirmation of entrance block in all 
clinically relevant targeted PVs after adenosine/ isoproterenol challenge. 
Touching up with focal catheter will be considered as acute procedural 
failure. 
Acute reconnection identified by adenosine/isoproterenol challenge. 
Among all clinically relevant targeted PVs and by subject
Rate of PV ablation by a non-study catheter (touch-up) among all 

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clinically relevant targeted PVs and by subject
Rate of repeated ablation within the 12M FU period, including timing 
(blanking period or after blanking) and rate of PV reconnection
6.1.5.2.
Selection of method and time to evaluate, record and analyze the 
effectiveness parameters
1) Long term effectiveness will be evaluated and recorded during effectiveness 
evaluation period (day 91 to day 365 post index procedure) by ECG and 24h 
Holter at 3 months, 6 months and 12 months follow-up points. Recurrence 
during blanking period (day 1 to day 90 post index procedure) is not considered 
as long term effectiveness failure.
2) Acute effectiveness will be evaluated and recorded at the end of procedure by 
the method of adenosine/isoproterenol challenge.
3) All the repeated ablations will be evaluated and recorded during the study. 
For the analysis of the above endpoints, see Section 7.
6.1.6. Safety evaluation method
6.1.6.1.
Description on safety parameters
Safety endpoints include
1) Procedure and device safety: The incidence of Primary Adverse Events (Aes) 
(within seven (7) days of the ablation procedure which uses investigational 
devices per protocol, including the initial and repeat procedures). PAEs 
include the following Adverse Events (Aes): Atrio-Esophageal Fistula*,
Cardiac Tamponade**,***/ perforation**, PNP (permanent)+, Pulmonary Vein 
Stenosis++, Device or procedure related death+++, Stroke/ CVA†,††, Major 
Vascular Access Complication Bleeding, Thromboembolism, Myocardial 
Infarction, TIA, Pericarditis, Pulmonary Edema (Respiratory insufficiency), 
Heart Block, Vagal Nerve Injury/ Gastroparesis
* Atrio-esophageal fistula occurring up to 90 days post AF ablation process 
procedure will be considered a PAE.
**Cardiac Tamponade/Perforation occurring up to 30 days post AF ablation 
process procedure will be considered a PAE
*** Hemodynamic compromise or instability is defined as Systolic BP < 80 
mm Hg.
+ Absent phrenic nerve function as assessed by a sniff test. Refer to Table 4
for permanent phrenic nerve paralysis definition.
++ Pulmonary Vein Stenosis occurring anytime during the 12-month follow 

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
Administer a heparin bolus prior to transseptal puncture.

An ACT≥350 seconds prior to ablation and throughout the procedure is 
recommended, and An ACT≥300 seconds is required.

An ACT below 300s requires additional bolus of heparin until a minimal 
targeted ACT of 300s is reached. It is REQUIRED to check ACT levels 
every 12-18 minutes during the ablation procedure to ensure an ACT target 
of ≥300 seconds.

Flush all tubing and sheath continuously with heparinized saline.
FOLLOWING the procedure

Anticoagulation therapy is REQUIRED for at least 2 months following 
ablation.

Decisions regarding continuation of systemic anticoagulation beyond 2 
months post ablation should be based on the subject’s stroke risk profile. 
Per HRS guidance systemic anticoagulation is recommended be continued 
beyond two months post-procedure in subjects with a CHA2DS2-VASc 
score of ≥ 2 (unless deemed contraindicated based on clinical 
considerations). 

AAD management:
o During this study, current AF management guidelines and the 
institution’s standard of care practices are to be followed as closely 
as possible for AAD therapy.
o A Class I and/or Class III AAD can be administered for AF during 
the blanking period and terminated before the end of the blanking 
period. If a Class I/III AAD is prescribed /administered after day 90 
post procedure or oral amiodarone is prescribed/administered at any 
time post procedure, it MUST be accompanied by documentation of 
arrhythmia. If a Class I and/or Class III AAD is continued or started 
past Day 90, the subject will be considered a primary effectiveness 
failure. If oral amiodarone is prescribed and/or taken at any time post 
index ablation procedure, the subject will be considered a primary 
effectiveness failure.

PPI administration following the procedure is at investigator discretion. 

Additional medications needed to treat clinical indications are at 
investigator discretion.

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6.3.2. Device operation specification
Please refer to IFU of IRE Generator（D-1417-01-I）and Circular IRE Catheter
（D-1412-01-SI）
6.4.
Study procedure
6.4.1. Screening and Informed Consent
Candidates presenting to the institution with symptomatic PAF 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. Sites will be instructed to screen all subjects who require a 
documented ablation procedure for symptomatic PAF without regard to sex or 
race.
The study investigator or designated member of the research team will obtain 
written informed consent from the subject. The patient informed consent 
procedure must be done within 90 days before the actual study procedure takes 
place. The background of the proposed study and the potential benefits and risks 
of the study should be explained to the subject. The subject or legal representative 
must sign the consent form prior to any study-specific exams or tests are provided 
to them that fall outside of the standard of care. The consent form used must have 
prior approval from the CAs and study site's EC. Failure to obtain informed 
consent renders the subject ineligible for participation in the study.
The investigator and/or designee must also clearly document the process of 
obtaining informed consent in the subject’s source documents. The voluntary 
process of informed consent confirms the subject’s willingness to participate in 
the study. It’s the investigator’s responsibility to ensure that the informed consent 
process is performed in accordance with Medical Device Good Clinical Practice 
(MD-GCP) and with applicable local and national regulations. If new information 
becomes available that can significantly affect a subject’s future health and/or 
medical care, this information shall be provided to the subject(s) affected in 
written form. If relevant, all affected subjects shall be asked to confirm their 
continuing informed consent in writing by dating and signing an amended ICF.
Each subject screened for enrollment in the clinical investigation who signs the 
patient ICF will be enrolled into the study. No subject should undergo any clinical 
investigation specific tests or examinations that fall outside the standard of care 
without first signing the patient ICF for this clinical investigation.
6.4.2. Pre-Procedure/Baseline Assessments
Below pre-procedure assessments and data collection must be performed prior to 

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the ablation procedure.
• Patient Information and Consent (procedure must be done within 90 days of 
consent)
• Demographics (age, gender, etc).
• Medical history, including but not limited to arrhythmia, heart disease, 
thromboembolic events, lung/respiratory problems.
o AF history (first evidence of AF, number of episodes, symptoms, etc).
o NYHA Functional Class Scale.
o CHA2DS2 VASc Score. CHA2DS2 VASc will be scored for all 
subjects. 
o Vital signs (length, weight, etc.)
o Medication history: Medication history (cardiac medication, AAD 
medication, anticoagulation regimen and any other clinically 
significant medication history) shall be gathered by interview or 
from medical records following enrolment but prior to the ablation 
procedure and should be recorded in the eCRF.
o Anticoagulation therapy: Anticoagulation therapy (NOAC or low 
molecular weight heparin) MUST be in place at least 24 hours prior 
to ablation procedure
• Physical exam
• Pregnancy test must be done on all women of childbearing age and potential 
within 72-hours prior to the procedure and documented in the subject’s 
medical chart.
• Imaging (TTE or other acceptable equivalent cardiac imaging – i.e. CT/MRI) 
within 6 months prior to procedure to assess the LA and LVEF. Must be 
collected within 6 months prior to procedure, in case of the imaging 
assessment is older than 6 months LA/LVEF, dimensions shall be re-
measured during the index procedure prior to insertion of the study catheter. 
In case of re-measurements before study catheter insertion fail to meet the 
LA and/or LVEF criteria, the subject will be considered as not meeting 
eligibility and will be excluded.
• Imaging for detection of left atrial thrombus or other structural 
contraindications to an ablation procedure is mandatory within 48 hours 
prior to ablation procedure. Presence of a thrombus will require 

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Figure 3: 
CCI
CCI

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6.5.2.
CCI
CCI

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CCI

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CCI

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CCI

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6.5.3. Collection of Ablation Procedure Data for Post-Analysis (non-SOC)
At the completion of the study ablation procedure, two back-up copies of the 
CARTO®3 and generator system log files will be made. One copy should be kept 
at the site within the investigator site or patient binders, and one fully anonymized 
copy will be provided to/collected by the Sponsor.
6.5.4. Data Collection during Study Ablation Procedure
Procedural data collection will be done through anonymized (or de-identified) 
generator files, anonymized (or de-identified) CARTO®3 data files, procedural 
worksheets and subject medical files. Documentation of procedural data will be 
kept in the subject’s CRF, anonymized (or de-identified) back-up generator files 
and back-up CARTO®3 datafiles for study analysis. The following information 
will be collected during the procedure, including but not limited to:
• Technical parameters are collected via CARTO® datafiles and generator 
files, including but not limited to:
o Number of PFA applications
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o Ablation locations/ targets
o Energy delivered
o PFA application time
o Ablation settings
o Ablation lesion information will be collected in the CARTO®3 
system and IRE Generator
• Other procedural parameters are collected via Electronic Data Capture 
(EDC), including but not limited to:
o Use of a non-study catheter for PVI
o Number of PFA applications per target PV
o Number of RF applications required with a non-study catheter
o PVI confirmed with Lasso® or PentaRay or Circular IRE Catheter
o PV acute reconnection (early or dormant)
o Procedure time (from first femoral puncture to last catheter out)
o Mapping time (start mapping - end mapping)
o Total fluoroscopy time
o Total study catheter LA dwell time (from first study catheter insertion 
in LA until study catheter removal from LA)
o ECG data
o Total fluid delivered via study catheter
o Total fluid delivered via intravenous line (if captured)
o Fluid output (if captured)
o Device deficiency information (if applicable)
o Procedural medication (paralytics)
o Anesthesia type
6.5.5. Repeat Ablation Procedures
Repeat procedures may be performed at the discretion of the investigator. Repeat 
procedures for AF/AT/AFL of unknown origin+ recurrences during the blanking 
period (90 days post index procedure) must be conducted with the investigational 
device for ablating PV reconnections. More than 1 repeat procedure for AF/AT/AFL of 

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unknown origin+ during the blanking period is considered a failure mode for 
primary effectiveness. Procedures for CTI dependent flutter in the follow up 
period are not considered repeat procedures per protocol. 
Repeat procedures performed after the blanking period may be managed per 
investigator discretion using a commercially available ablation catheter and 
generator. The follow-up schedule will remain based on the initial ablation 
procedure.
For the repeat procedures for AF/AT/AFL of unknown origin+, investigators must
collect and provide information on location of reconnections of PVs and in case 
of atrial flutter recurrence, confirm if CTI dependent flutter or AFL of unknown 
origin.
+AFL of unknown origin is defined as all AFL except those CTI dependent AFL 
as confirmed by 12 or 15 leads ECG or entrainment maneuvers in an EP study.
6.5.6. Post-Ablation Follow-up Schedule
The subject will be required to complete follow-up visits through 12 months post 
initial ablation procedure. Follow-up will be done at discharge, 7 day +3 days
(phone call or clinic visit), 1 month ± 7 days (phone call or clinic visit), 3 month 
±14 days, 6 month ± 30 days and 12 month ± 30 days (clinic visit). Follow-up 
visit schedule should be based on the date of the index study ablation procedure 
and will not reset if subject undergoes a repeat AF ablation procedure.
Prior to hospital discharge, the following assessments should be performed:
• Physical exam MUST be performed pre-discharge.

If physical exam demonstrates new abnormal neurological 
findings as compared to the one performed at baseline, a formal 
neurological consult and examination with appropriate imaging 
(i.e., DW-MRI) needs to be done to confirm or rule out any 
suspected diagnosis of stroke.

Diagnosis of stroke/CVA must be confirmed by at least one of the 
following:
o Neurology or neurosurgical specialist
o Neuroimaging procedure (MR or CT scan or cerebral 
angiography)
o Lumbar puncture (i.e., spinal fluid analysis diagnostic of 
intracranial hemorrhage)

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o Stroke: (diagnosis as above, preferably with positive 
neuroimaging study)

Minor-Modified Rankin sore<2 at 30 and 90 days

Major-Modified Rankin score>=2 at 30 and 90 days

MRS assessments should be made by certified 
individuals
• Medication regimen (Cardiac, anti-coagulation, PPIs and AE related)
• TTE should be performed to evaluate pericardial effusion
• AEs events
• AF/AT/AFL recurrence
• 12 or 15 leads ECG
At 7 day, 1-, 3-, 6-, 12-month follow-up, and at any unscheduled visits, the 
following assessments will be performed:
• Physical exam: exam should be performed at all clinical visits (except at 7 
day follow-up)
• 12 or 15 leads ECG. Data from 12 or 15 leads ECG recordings will be 
collected at 3-, 6- and 12-month follow-up visits. ECG data will be collected 
at unscheduled visits if completed as standard of care.
• 24 Hour Holter: Holter monitor will be used at 3-, 6- and 12-month follow-
up visits to monitor the subjects’ heart rhythm for 24 hours continuously.
• Cardiac CT/MRA image: Any subjects who have symptoms suggestive of 
PV stenosis should undergo CT/MRA imaging.
• Adverse Events: AEs must be collected from the time the subject signs the 
informed consent onwards.
• AF/AT/AFL recurrences: for subjects with AFL recurrence identified though 
Holter monitoring, a 12 or 15 leads ECG MUST be collected.
• Medication: Cardiac and Anti-coagulation medication regimen, AE related
• Repeat ablation: any ablation procedure performed after the index procedure 
will be recorded at 3-, 6- and 12-month follow-up as well as at any 
unscheduled visits.
• Cardiac related hospitalization and cardioversions

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• Subject completion/ discontinuation form (12-month)
Early Termination Visit
If early termination of the study is required due to safety concerns, each site will 
undergo a monitoring visit to conclude any outstanding issues, collect all 
outstanding CRF information, verify device accountability, and discuss any other 
items relevant to the conclusion of the study. Any enrolled subjects will continue 
to be followed per the study protocol requirements. In case of early termination 
due to safety concerns, reporting to EC and CA may be required per local 
regulations.
Unscheduled Visit
If a subject returns for a potential study related cardiovascular or neurological 
visit outside of the protocol-defined visit schedule provided in table 2, the visit 
will be considered “unscheduled” (UNS). An investigator may request an 
unscheduled visit in the presence of a new or worsened cardiovascular condition 
or neurological deficit. If the unscheduled visit is for a repeat ablation procedure, 
the protocol follow-up schedule is based on the index ablation procedure. For all 
unscheduled visits, an unscheduled visit eCRF must be completed and the subject 
must also return for their next scheduled study visit per clinical investigational 
plan.
6.6.
Monitoring plan
This study is carried out according to the Good Clinical Practice for Medical 
Device Trials and relevant international laws and regulations, criteria, etc., such 
as the Declaration of Helsinki.
The sponsor bears the monitoring responsibility for the clinical trial and will select 
the qualified monitor to execute the monitoring responsibility.
The monitor should comply with the relevant laws and regulations and the 
standard operating procedure (SOP) established by the sponsor regarding the 
monitoring to monitor each phase of this study.
The monitor should contact and visit the investigators at a regular basis and 
perform on-site visit/monitoring for the study. The monitor should conduct a visit 
when the first subject is enrolled in each site and conduct a necessary visit at a 
regular basis during the study.
The monitoring includes the visit to study sites, verification of source data, 
communication with investigators and study sites, ensuring that this study is 
carried out strictly in compliance with the trial protocol and the requirements of 
such regulations as Good Clinical Practice.

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analyzed in the full analysis set (FAS) and the safety analysis set.
The descriptive statistics of continuous variables will include the number of 
subjects with valid data, number of missing, mean, standard deviation, quartiles, 
minimum and maximum. The descriptive statistics of categorical variables will 
include the frequency and percentage. The number of missing will not be included 
in the denominator for percentage calculation. 
The data analysis plan will be documented in detail in the Statistical Analysis Plan.
CCI

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Analysis of secondary endpoints
All secondary endpoints will be analyzed on the FAS. 

Acute Procedural Success: the number and percentage of patients with acute 
procedural success will be calculated, and the two-sided 95% confidence 
CCI

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interval (CI) will be calculated by the exact (Clopper-Pearson) test method. 

Acute reconnection identified by adenosine/isoproterenol challenge among all 
clinically relevant targeted PVs and by subject: the number and percentage of 
PVs/patients with acute reconnection will be calculated, and the two-sided 95% 
CI will be calculated by the exact (Clopper-Pearson) test method.

Rate of PV ablation by a non-study catheter (touch-up) among all clinically 
relevant targeted PVs and by subject: same statistical analysis method as acute 
reconnection.

Rate of repeated ablation within the 12M FU period: same statistical analysis 
method as acute procedural success.
The secondary endpoints will not be used for statistical inference, but for 
descriptive purposes. Therefore, multiplicity will not be adjusted.
Analysis of safety endpoints
The safety endpoints will be analyzed in the safety set. 
AEs will be summarized, including the number of AEs and the number and 
percentage of subjects experiencing any AEs. All PAE, SAEs and all procedure-
/device-related AEs will analyzed in same way. The severity, relationship, AE 
treatment intervention, seriousness and outcome of all AEs will be described.
In addition, all AEs, PAE, serious and non-serious AEs will be summarized 
according to the system organ classification and preferred terms of MedDRA, and 
a list will be generated, including but not limited to subject identification number, 
age, AE term, start and end time (corresponding duration post procedure), severity, 
relationship, AE treatment intervention, seriousness, and outcome.
Handling of missing value
Subjects will be contacted by different means, such as by telephone, to avoid 
missing value. 
For the primary endpoint, missing primary endpoint data of the subjects in the 
FAS will be excluded from the final primary effectiveness analysis as described 
in “Primary analysis of primary endpoint” of Section 7.5. 
For those who had the investigational device inserted but not ablated, they would 
be replaced, and new subjects should be screened and enrolled to ensure total 110 
evaluable non-roll-in subjects. 
For baseline information, operational information, or secondary endpoints, all 
observed data will be used for analysis. Missing data imputation will not be 

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the data analysis will be performed.
9.
Feasibility Analysis
9.1.
Possibility analysis on success
The isolation of pulmonary veins (PVI) from the left atrium is the cornerstone for 
AF ablation procedures. The clinical data from different technologies and catheter 
designs have shown that PVI is safe and effective in treatment of paroxysmal AF.
The BWI PFA system have been proven with features of non-thermal, irreversible, 
and cardiac tissue selection, which might be used to treat atrial arrhythmias. In 
pre-clinical studies, it showed that the predicate products were safe and could 
produce durable lesions.
Although there was limited clinical data about PFA technology in AF ablation, the 
features of non-thermal and cardiac tissue selection make this technology safer 
for structures adjacent to the myocardium. So, it is unlikely that the study will be 
terminated due to safety problems.
The investigational device is provided free of charge, which will not increase the 
burden of the subjects, so the difficulty in recruiting and screening subjects is 
acceptable. 
9.2.
Possibility analysis on failure
Long term effectiveness is unknown for PFA technology. There is limited clinical 
data for this technology in cardiac ablation area. there may be some undetected 
problems that may result in some unforeseen results in this study.
Patients will be followed 3 times in clinic and 2 time by phone and have ECG and 
24h Holter at 3M/6M/12M follow-ups, which is not SOC and would be 
challenging in following up. 
10. Quality Control of Clinical Trial
During the clinical study, the sponsor and investigator should execute their 
respective responsibilities according to the Good Clinical Practice for Medical 
Device Trials  and applicable relevant Chinese and international regulations. 
They should also strictly follow the clinical trial protocol, to ensure the quality of 
clinical trial.
The sponsor should, according to the requirements of the clinical trial protocol, 
organize the training on the clinical trial protocol and the use and maintenance of 
investigational product for all investigators participating in the trial, to ensure 
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investigational products.
During the implementation of study, the sponsor is responsible for monitoring 
each phase of clinical trial. The clinical monitor designated by the sponsor or 
designated representative should comply with the relevant SOP and clinical trial 
protocol that are established by the sponsor to monitor the clinical trial, to ensure 
the complete, accurate, true, and reliable data.
To ensure the quality of study, the sponsor may authorize the qualified QC or 
auditor to audit the clinical trial as needed. The investigator should allow the 
auditors to access to the original data and documents related to this study after 
receiving the notification.
When the medical products administration or other health administrative authority 
appoints the inspection personnel to carry out inspection, the study sites and 
investigators should cooperate and immediately notify the sponsor.
11. Ethical Issues and Informed Consent of Clinical Trial
11.1. Ethical considerations
The study should comply with Chinese laws and regulations, the Declaration of 
Helsinki and other international consensus, to protect the rights, safety, and health 
of subjects, including at least the following contents:
1) Ensure that the subjects are fully informed and agree to participate in the study 
voluntarily;
2) Respect and protect the privacy of subjects, and keep the records that may 
identify subjects confidential;
3) The production of the investigational medical device should meet relevant 
requirements of the applicable medical device quality management system; 
the use of the investigational medical device should meet the requirements of 
their IFUs, the protocol and relevant operation guidance;
4) Select the qualified study sites and investigators;
5) A subject has the right to withdraw from the study at any time for any reason 
without prejudice to their future medical care by the physician or the 
institution;
6) The study protocol and amendment, the ICF and amendment and other study-
related applicable documents should be approved by the EC before 
implementation.
11.2. Approval of trial protocol

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Before the trial protocol is submitted to China Food and Drug Administration (if 
necessary), the EC and other authorities for approval, the internal review and 
approval should be completed according to the company's SOP.
The clinical trial protocol can be implemented only after the written approval from 
the EC is obtained.
11.3. Informed consent process 
11.3.1. Informed consent process
The written consent of all candidate subjects or their legal authorized 
representatives 
must 
be 
obtained 
prior 
to 
performing 
any 
study 
operations/procedures (except for SOC operation procedures). Once the 
investigator determines that the subjects are suitable for participating in this study, 
the investigator must explain the study background and procedures, possible 
benefits and risks, etc. to the subjects or their legal authorized representatives. 
Only the subject who signs the ICF (Informed Consent Form) of the latest version 
that is approved by the EC (Ethics Committee (EC)) prior to participating in the 
study is eligible to participate in this study. The subject who does not sign the 
written ICF is not eligible to participate in this study.
Each subject (or legally authorized representative) must sign and date the ICF of 
the latest version that is approved by the EC (and other documents as per local 
regulations) prior to performance of any study-related activity or procedure, that 
is not standard of care and the study has been fully explained.
The voluntary process of obtaining written informed consent confirms the 
subject’s willingness to participate in the study. The Investigator and/or designee 
must clearly document the process of obtaining informed consent in the subject 
clinical record. The investigator has responsibilities to ensure the process of 
obtaining the informed consent is implemented according to It is the Investigator’s 
responsibility to ensure that the informed consent process is performed in 
accordance with the Good Clinical Practice for Medical Device Trials and 
relevant regulations, such as Declaration of Helsinki.
12. Device Management
In this study, the sponsor will provide all investigational devices. The package is 
clearly marked with "For Clinical Trial Only". All devices must be stored 
according to the conditions specified by the product label and IFU. The principal 
investigator is responsible for ensuring that the device is properly stored at the 
site.
The principal investigator or the person designated personnel by the principal 

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investigator must be responsible for all investigational devices throughout the 
clinical study and at the end of the study. During the study, the investigational 
devices must be kept in a locked or safe place. Inventory records of all devices 
received, used, or returned must be maintained during the clinical trial. The 
principal investigator must allow the monitor to enter the safe place where the 
investigational devices are kept in order to check the inventory. At the end of the 
clinical trial, all unused investigational devices must be returned to Johnson & 
Johnson Medical (Shanghai) Ltd., and an appropriate investigational device return 
form must be provided.
12.1. Packaging and labeling of investigational devices
All investigational devices provided by the sponsor in this study are prepared, 
packaged and labeled by qualified staff or designated personnel of the sponsor in 
accordance with the company's SOP, Good Manufacturing Practice for Medical 
Devices (GMP) and relevant local laws/regulations.
The label of each device meets the requirements of guidelines issued by regulatory 
authorities, GMP, local laws and regulations and company's SOP, and indicates 
that the investigational product is only for clinical trial.
12.2. Shipment of investigational devices
The sponsor or designated personnel of the sponsor will supply the devices to the 
study sites according to the device storage conditions in the device IFU.
12.3. Management of investigational devices
The sponsor will be responsible for providing qualified investigational products 
to the study sites. Each study site should designate related person to be responsible 
for the management of investigational devices. When the study sites receive the 
investigational products, they should check the investigational products and 
ensure that the packages of the investigational products are complete, the quantity 
is correct, and the transportation conditions meet the requirements.
During the study, the designated person is responsible for recording and counting 
the usage of the investigational products.
Records related to the receiving, distribution, use, recovery and disposal of 
investigational products should be kept in accordance with the requirements of 
Medical Device Good Clinical Practice (MD-GCP).
The investigators should ensure to use the investigational medical device only for 
the subjects of this clinical trial.
The principal investigator must allow the monitor to enter the safe place where 

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the investigational devices are kept during the clinical trial in order to check the 
inventory. At the end of the clinical trial, the unused investigational devices must 
be returned together with the relevant investigational device return form.
12.4. Return and destruction of investigational devices 
All unopened and unused (e.g., expired), opened but unused, damaged, mislabeled 
or malfunctioning investigational devices should be sent back to the address 
designated by the sponsor. The corresponding form should be completed, and the 
devices should be properly returned to the address specified by the sponsor. The 
appropriate form(s) must be completed, and the device must be returned by 
courier to an address specified by the sponsor.
13. AEs and Device Complaints reporting
13.1. AEs recording
An adverse event is any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory findings) 
occurring during a clinical study, whether or not related to the study device or 
ablation procedure.
The following clinical events will not be considered an adverse event for this 
clinical study:
• Any medical condition that is present at the time of screening. Such 
conditions should be added to the medical history if not previously reported. 
However, if the study subject’s condition deteriorates at any time during the 
study, it should be recorded as an AE.
• Minor pericarditis attributable to the ablation procedure defined as pleuritic 
chest discomfort with or without pericardial rub and ECG changes.
• A trace/ trivial pericardial effusion that is asymptomatic, requires no medical 
intervention, and does not extend hospitalization will not be considered an 
adverse event.
• Postoperative incision pain, fever, incisional scar formation and abnormal 
lab test values are expected to occur and should not be recorded as AEs 
unless the investigator considers incision pain, fever, incisional scar 
formation and abnormal lab test values exceed the normal expected range 
for postoperative response or are related to the investigational device.
The following clinical events will not be considered an adverse event for this 
clinical study but will be captured in the database separately:

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• Recurrence of pre-existing AF/AT/AFL of unknown origin+
• AF/AT/AFL of unknown origin requiring direct current cardioversion or 
pharmacological cardioversion (and accompanying hospitalization) during 
the blanking period. However, new onset of left atrial flutter occurring post 
ablation is an AE. For subjects with AFL recurrence identified through 
Holter monitoring; a 12 or 15 leads ECG MUST be collected.
• Re-ablation for AF or pre-existing AT/AFL of unknown origin+ (including 
accompanying hospitalization) itself is not an AE. However, any 
complication associated with the repeat ablation procedures is considered 
an AE and shall be reported within the applicable timelines.
From signing the ICF by the subject, the investigator should determine whether 
an AE occurs and determine its relationship to the investigational device or 
procedure at each evaluation for the subjects recruited for the clinical study.
Other AEs, investigational device malfunctions and other product issues must be 
recorded in the medical record and entered in the e-CRF.
13.2. Classification
Any of the following events, and any death or hospitalization while on study, is 
to be reported to the sponsor immediately when investigator is awarness. The 
sponsor may request additional information after the initial notification
13.2.1. Primary Adverse Event
A primary AE is one of the following events occurring within seven (7) days 
following an AF ablation procedure with the Circular IRE Catheter when used 
with IRE generator per protocol. Table 4 provides the PAEs and their descriptions.
A Clinical Events Committee (CEC) will be implemented to adjudicate the 
primary adverse events. The CEC will operate as described in the CEC Charter.
All reported Primary AEs will be monitored until they are adequately resolved or 
explained. The Clinical Events Committee (CEC) is to adjudicate the primary 
adverse events and operate following the regulations of the Committee.
Table 4: Primary adverse events and description/criteria
Primary AE
Description/ Criteria
Death (device or procedure related)
Subject death directly related to the device or procedure and 
occurs at any time during or after the procedure.
Atrio-Esophageal Fistula*
Is defined as a connection between the atrium and the lumen of 
the esophagus. Evidence supporting this diagnosis includes 
documentation of esophagus erosion combined with evidence of 
a fistulous connection to the atrium such as air emboli, an 

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embolic event, or direct observation at the time of surgical 
repair. A CT or MRI scan is the most common method of 
documentation of an atrio-esophageal fistula.
Cardiac 
Tamponade**,***/Perforation**
The development of a significant pericardial effusion during or 
within 30 days of undergoing an AF ablation procedure. A 
significant pericardial effusion is one which results in 
hemodynamic compromise, requires elective or urgent 
pericardiocentesis, or results in a 1 cm or more pericardial 
effusion as documented by echocardiography. Cardiac 
tamponade should also be classified as "early” or “late” 
depending on whether it is diagnosed during or following initial 
discharge from the hospital.
Myocardial Infarction
The presence of any one of the following criteria:
•
Detection of ECG changes indicative of new ischemia 
(new ST-T changes or new LBBB) which persists for 
more than 1 h
•
Development of new pathological Q waves on an ECG, 
and
•
Imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality
Stroke/ Cerebrovascular Accident
Rapid onset of a focal or global neurological deficit with at least 
one of the following: change in level of consciousness, 
hemiplegia, hemiparesis, numbness, or sensory loss affecting 
one side of the body, dysphasia or aphasia, hemianopia, 
amaurosis fugax, or other neurological signs or symptoms 
consistent with stroke.
Duration of a focal or global neurological deficit ≥24 h; or <24 
h, if therapeutic intervention(s) were performed (e.g., 
thrombolytic therapy or intracranial angioplasty); OR available 
neuroimaging documents a new hemorrhage or infarct; or the 
neurological deficit results in death.
No other readily identifiable non-stroke cause for the clinical 
presentation (e.g., brain tumor, trauma, infection, hypoglycemia, 
peripheral lesion, pharmacological influences)† Confirmation of 
the diagnosis by at least one of the following:
•
Neurology or neurosurgical specialist
•
Neuroimaging procedure (MR or CT scan or cerebral 
angiography)
•
Lumbar puncture (i.e., spinal fluid analysis diagnostic of 
intracranial hemorrhage)
Stroke: (diagnosis as above, preferably with positive 
neuroimaging study)
•
Minor—Modified Rankin score <2 at 30 and 90 days††
•
Major—Modified Rankin score ≥2 at 30 and 90 days
Thromboembolism
Formation of a clot (thrombus) inside a blood vessel causing 
obstruction to blood flow. The thrombus can migrate (embolus) 
and obstruct distal vascular sites. Diagnostic tests to help detect 
thromboembolisms may include but are not limited to 
angiography (pulmonary or distal), ventilation-perfusion (V/Q) 
scans, venography, Doppler ultrasonography, spiral CT, and 
echocardiography. For the purposes of this study, silent 

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(asymptomatic) cerebral embolism will not be considered a 
PAE.
Transient Ischemic Attack
New focal neurological deficit with rapid symptom resolution 
(usually 1 to 2 h), always within 24h. Neuroimaging without 
tissue injury.
Phrenic Nerve Injury / Diaphragmatic 
Paralysis
Absent phrenic nerve function as assessed by a sniff test. A 
phrenic nerve paralysis is considered to be permanent when not 
resolved at the final follow-up.
Heart Block
Impairment of AV conduction requiring intervention (e.g., 
temporary or permanent pacemaker) due to iatrogenic cause 
(e.g., inappropriate RF application, traumatic maneuvering of 
catheter or other intracardiac devices).
Pulmonary Vein Stenosis+
A reduction of the diameter of a PV or PV branch. PV stenosis 
can be categorized as mild <50%, moderate 50-70%, and severe 
70% reduction in the diameter of the PV or PV branch.
PV stenosis (> 70% PV narrowing) regardless of the presence or 
absence of symptoms and PV stenosis with ≥ 50% PV 
narrowing when accompanied with relevant and related 
symptoms that cannot be explained by other etiologies will be 
considered a primary adverse event.
Pulmonary 
Edema 
(Respiratory 
Insufficiency)
Respiratory insufficiency resulting in pulmonary complications 
necessitating intubation or other significant intervention 
(including diuretics administered specifically for treating 
pulmonary edema or ICU hospitalization requiring oxygen 
administration but not intubation). Exclusion criteria include:
•
Pneumonia – infiltrate, fever and leukocytosis
•
Acute Respiratory Distress Syndrome
Vagal Nerve Injury/ Gastroparesis
Injury to the vagal nerve that results in esophageal dysmotility 
or gastroparesis. Vagal nerve injury is considered to be a major 
complication if it prolongs hospitalization++++, requires
hospitalization, or results in ongoing symptoms for more than 30 
days following an ablation procedure.
Pericarditis
Should be considered a major complication following ablation if 
it results in effusion which leads to hemodynamic compromise 
or requires pericardiocentesis, prolongs hospitalization++++ by 
more than 48 h, requires hospitalization++++, or persists for 
more than 30 days following the ablation procedure.
Major Vascular Access Complication 
/ Bleeding
Major Bleeding:
A major complication of AF ablation if it requires and/or treated 
with transfusion or results in a 20% or greater fall in HCT.
Major Vascular Access Complication:
Defined as hematoma, an AV fistula, or a pseudoaneurysm 
which requires intervention such as surgical repair or 
transfusion, prolongs the hospital stay, or requires hospital 
admission.
* Atrio-esophageal fistula that occurs greater than one week (7 days) post-procedure and up to 90 days 
post-procedure is considered and analyzed as a PAE.
** Cardiac Tamponade/Perforation occurring within 30 days of the AF ablation process will be considered 
Primary AEs

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*** Hemodynamic compromise or instability is defined as Systolic BP < 80 mm Hg.
+ Pulmonary Vein Stenosis will be considered as a PAE if it occurs anytime during the 12- month follow up 
period.
† Subjects with non-focal global encephalopathy will not be reported as a stroke without unequivocal 
evidence based upon neuroimaging studies.
†† Modified Rankin score assessments should be made by certified individuals. ++++“Hospitalization” 
means the event necessitated an admission to a health care facility e.g., with at least an overnight stay. 
Emergency room visits that do not result in admission to the hospital should be evaluated for one of the 
other serious outcomes.
13.2.2. Serious AEs
A SAE is any AE that results in a death or a serious deterioration in the health of 
the subject during the clinical trial, including a life-threatening illness or injury, a 
permanent impairment of a body structure or a body function, in-patient 
hospitalization or prolongation of existing hospitalization*, medical or surgical 
intervention to prevent permanent impairment of a body structure or a body 
function; or results in fetal distress, foetal death or congenital abnormality, 
congenital anomaly, etc.
If it is a disease that exists before the scheduled hospitalization and/or medical 
intervention, or the operation required by the protocol but no serious deterioration 
in health, it will not be regarded as an SAE.
“Hospitalization” means the event necessitated an admission to a health care 
facility e.g., with at least an overnight stay. Emergency room visits that do not 
result in admission to the hospital should be evaluated for one of the other serious 
outcomes.
*Planned hospitalization for a condition present prior to the participant’s 
enrollment in the study will not meet the definition of an SAE but should 
nevertheless be included in routine study reporting.
13.2.3. Non-Serious AEs
A non-serious AE is any event that results in minimal transient impairment of a 
body function or damage to a body structure and does not require any intervention 
listed under the criteria for “Serious Adverse Event.” Non-serious adverse events 
require routine reporting via EDC.
13.2.4. Anticipated AEs
An anticipated AE is one that has been reported in previous studies of cardiac 
ablation and can be anticipated in this current study as per the risk analysis. 
Appendix II provides a comprehensive list of anticipated AEs. If listed then report 
event as anticipated.
13.2.5. Unanticipated Serious Adverse Device Effects

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A (serious) adverse device effect (SADE) is any (serious) adverse effect on 
subjects’ health, safety, rights, welfare, and life-threatening problems including 
death, which is caused by, or associated with the study device. Accordingly, 
relationship to device or study is a crucial assessment by investigators. An 
unanticipated adverse device effect (UADE) or unanticipated serious adverse 
device effect (USADE) is any ADE or SADE that has not been previously 
identified in nature, severity, or degree of incidence in the study plan or risk 
analysis report. An investigator shall submit to the reviewing EC a report of any 
unanticipated adverse device effect occurring during an investigation per EC
requirements.
13.2.6. Intensity or Severity, Outcome and Causality
Intensity (or severity) of AEs is defined as follows as table 5:
Table 5. Definition of intensity (or severity) of AEs
Mild
Awareness of sign or symptom that does not interfere with the subject’s usual activity or 
is transient, resolved without treatment and with no sequelae.
Moderate
Interferes, but does not hinder, the subject’s usual activity and may require treatment.
Severe
Symptom(s) causing severe discomfort and significant impact on the subject’s usual 
activity and requires treatment or intervention.
AE outcomes are assessed according to the following classifications as table 6:
Table 6. Definition of AE outcomes
Recovered/ Resolved 
Subject recovered withoutsequelae..
Recovered/Resolved 
Subject recovered with sequelae.
Not 
recovered/ 
resolved, 
onging
AE is ongoing without improvement or worsening in overall condition
Recovering/Resolving
Subject's condition is improving but residual effects remain.
Not recovered/ resolved
, 
worsening
AE is ongoing with worsening in overall condition.
Fatal
Subject died as a result of the adverse event, whether or not the AE is 
related to the device or procedure. Note: deaths from any cause occurring 
on this study are to follow expedited reporting.
Others
Others：like AE outcome is unknown (e.g., subject lost to follow-up)
The causal relationship should be rated as table 7:
Table 7. Definition of causal relationship
Caused by
Relation
Definition of Relation
Device
Definitely (Causal 
relationship)
The event is associated with the investigational device 
beyond reasonable doubt
Possible
The relationship with the use of investigational device 

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seems relevant and/or the event cannot reasonably be 
explained by another cause, but additional information my 
be obtained. Or the relationship with the use of 
investigational device is weak but cannot be ruled out 
completely
Unlikely
The occurrence of AE is more possibly related to other 
factors, or the temporal sequence did not reasonably show 
the relationship between product application and the event
Not related
Relationship to the investigational device can be excluded.
Study 
procedure
Definitely (Causal 
relationship)
The event is associated with the procedure beyond 
reasonable doubt.1
Possible
The relationship with the study procedure seems relevant 
and/or the event cannot reasonably be explained by 
another cause, but additional information may be obtained. 
Or the relationship with the study procedure is weak but 
cannot be ruled out completely
Unlikely
The occurrence of AE is more possibly related to other 
factors, or the temporal sequence did not reasonably show 
the relationship between study procedure and the event
Not related
Relationship to the study procedure can be excluded.
1 If event is deemed related to procedure, site should indicate whether related to index or repeat if applicable.
13.3. Device complaints
Device complaint refers to any defects of the marketed products regarding 
identification, quality, durability, reliability, safety, effectiveness or product 
performance that are reported in a written, electronic or oral manner. If there are 
any complaints about Johnson & Johnson’s products, the study site must inform 
the monitor and follow up and report them according to the procedures specified 
by the sponsor. After receiving the complaint information from the study site, the 
monitor will follow up and report it according to the manner and time limit 
specified by the sponsor, and coordinate with the study site on the return of 
relevant investigational products.
13.4. Device deficiencies
The device deficiency is defined as unreasonable risk occurred under normal use 
of medical device during the clinical trial, which may do harm to human health 
and life safety, such as label error, quality problem and fault.
13.5. Reporting procedures and contact information
The investigator should ensure to provide the sufficient treatment for any AEs of 
any subjects, including the laboratory test values with clinical significance and 
related to this study.
The investigator should report the AE to the sponsor through e-CRF within 2 

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weeks after learning of the AE. The investigator should record the nature, severity, 
treatment and outcome of AE, and determine whether it is related to the 
investigational device, medication or surgery specified in the trial protocol.
The investigator should follow up all AEs until the event is resolved (with or 
without sequelae), or if the event causes the permanent damage, it should be 
followed up until the event is stable and the clinical outcome is determined. When 
the event is not resolved or stable at the end of study, the medical monitor in this 
clinical study will decide whether it is necessary to collect the further follow-up 
information.
The investigator must report any SAE to the administrative department for 
medical device clinical trials of the study site, the sponsor and the EC within 24 
hours after learning of such SAE or device deficiency, and should provide further 
information if requested by the sponsor.
The investigator should record all device deficiencies and complaints occurred 
during the clinical trial, and contact the sponsor's monitor or corresponding 
contact person in time. Detailed reporting process and contact person are shown 
in the Safety Events Management Plan. According to the requirements of the 
sponsor, the defective investigational devices should be returned to the sponsor as 
much as possible.
For the SAE, the sponsor should, according to the regulatory requirements, report 
to other clinical trial institutions participated in the clinical trial, Ethics Committee 
and principal investigators, the drug administration department where the sponsor 
is located, the drug administration department where the clinical trial institution 
is located and health administration department, within 7 days of being informed 
of a death or life-threatening serious adverse event (SAE) associated with a 
clinical trial medical device, and within 15 days after being informed of non-death 
or non-life threatening serious adverse events associated with a clinical trial 
medical device or other serious security risk information, and shall take risk 
control measures.
14. Provisions for Deviation from Clinical Trial Protocol and the 
Amendment to Clinical Trial Protocol
The protocol deviation is defined as the circumstances that fail to comply with the 
requirements of clinical trial protocol intentionally or unintentionally.
The sponsor's investigator should record and report all protocol deviations in a 
timely manner. 
If protocol amendment is required, the sponsor or designated person should 

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submit the change data of trial protocol to the investigator, EC, etc. according to 
the relevant laws and regulations. All major amendments must be approved by the 
EC and regulatory authority (if needed) prior to implementing any changes to 
study procedures.
15. Direct Access to Source Data and Documents
The source data is defined as all information in the original record and its 
approved copy with regard to the clinical findings, observations and other 
activities in the clinical trial, which can be used for reproduction and evaluation 
of clinical trial. The source documents are documents in which the source data are 
recorded, including printed or electronic documents.
The information in the subject’s medical records and other study related 
documents (source documents) must be maintained and retained by the 
investigator. The investigator should allow the monitors and auditors/inspectors 
to look up, including but not limited to the following information:

Medical/physical condition of the study subject that meets the inclusion 
criteria in the trial protocol prior to participating this study;

Medical records in which informed consent process is recorded;

Operational description on use and implantation of the investigational product;

All examination results and follow-ups;

Examined printed output file or report (for example, X-ray film) that is dated 
and signed;

Description on AEs and follow-ups of AEs (description on events, severity, 
date of occurrence, duration, correlation with the investigational device, study 
procedures, outcome and treatment of AEs, concomitant medications when 
AE occur);

Description on device deficiencies

Study subject’s status at the end of the study or withdrawal from the study.
16. Finance and Insurance
See the relevant study contract and insurance document.
17. Contents of Clinical Trial Report
According to the regulatory requirements, the clinical trial report should include 
the following contents:
The clinical trial report should be consistent with the clinical trial protocol, mainly 
including:

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(I).
General information;
(II).
Summary;
(III).
Introduction;
(IV).
Clinical trial objective;
(V).
Clinical trial method;
(VI).
Clinical trial contents;
(VII).
General clinical information;
(VIII).
Investigational medical device and control medical device or control 
diagnostic and therapeutic method;
(IX).
Statistical analysis methods and evaluation methods adopted;
(X).
Clinical evaluation criteria;
(XI).
Organizational structure of clinical trial;
(XII).
Ethical description;
(XIII).
Clinical trial results;
(XIV).
AEs found in the clinical trial and their handling;
(XV).
Analysis and discussion of clinical trial results, especially the 
indications, scope of application, contraindications and precautions;
(XVI).
Clinical trial conclusion;
(XVII). Existing problems and improvement suggestions;
(XVIII). List of investigators;
(XIX).
Other conditions that need to be described;
18. Confidentiality Principle
The personal data of the subject participating in the trial is confidential; however, 
the EC, sponsor and health administrative authority and their authorized 
representatives may review the personal data of the subjects participating in the 
trial according to the established procedure.
The personal data of subjects should be kept confidential during the entire period 
of clinical study, and it should be ensured that the source data can be tracked 
through information. Therefore, a unique subject identification number (study site 
number and subject number) is used to identify all data of each subject reported. 
If the data is kept strictly confidential and it is ensured that the privacy of the 
subject has been protected, the data related to this study is available for the third 
party (for example, under the inspection of regulatory authority).
19. Agreement on Publication of Trial Results
If needed, an article for multi-center clinical trial will be prepared and published 

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in the prestigious scientific journal at the end of the study. No major results of any 
individual study site in this study are allowed to be published before the multi-
center trial results are prepared and published. In case of exceptions, such as 
analysis of pre-defined and non-pre-defined other endpoints, or such secondary 
analyses and other proposed investigations, prior approval of the sponsor is 
required. To timely extract the statement and publish, the second publication will 
be entrusted to the corresponding principal authors. The final analysis and review 
of all multi-center trial data are required to be approved by the sponsor.
20. Responsibilities of Parties Involved
20.1. Responsibilities of sponsor
The sponsor is responsible for the initiation, application, organization and 
monitoring of a clinical trial and is responsible for the quality of the clinical trial. 
This includes: select qualified study sites and their investigators; organize the 
preparation and revision of study related documents before or during the trial; 
provide necessary training for the investigators to carry out this clinical trial. 
Ensure that investigators follow the clinical trial protocol; provide qualified 
investigational products and other study related articles required for 
implementation of this trial according to the regulatory requirements; collect and 
report AEs, SAEs and device deficiencies according to regulations; coordinate 
and organize the clinical trial reporting and final registration application at the end 
of the study.
20.2. Responsibilities of study sites and investigators
The study sites should evaluate the relevant resources according to the features of 
investigational medical device prior to the clinical trial, so as to decide whether 
to carry out this clinical trial. The administrative department for medical device 
clinical trials of the study site should cooperate with the sponsor to submit the 
clinical study application to the EC and submit relevant documents according to 
regulations. The study sites should properly keep the records and basic documents 
of clinical trial according to relevant laws & regulations and the time limit agreed 
with the sponsor.
The investigator should ensure that relevant staff participating in the trial has 
enough resources and receive study-related training, and keep the training related 
documents, and should carry out the study according to the clinical trial protocol.
The study sites and investigators should ensure that the data, documents and 
records generated in the clinical trial are true, accurate, clear and safe, should 
accept and cooperate with the monitoring and audit of the sponsor, the supervision 
of the EC, as well as the inspection of the health administrative authority, and 

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provide all required records related to the trial. The investigators should ensure to 
complete all records and reports at the end of clinical trial. The investigators 
should also ensure that the received investigational medical devices are properly 
handled and recorded according to the requirements.
20.3. Responsibilities of other interested parties 
See the study-related contract.

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INVESTIGATOR’S STATEMENT:
I agree:
1. To carry out this clinical trial in strict compliance with Declaration of 
Helsinki, current laws and regulations of China, and the requirements of 
the trial protocol.
2. To accurately record all data required into the CRF and complete the 
clinical trial report on time.
3. The investigational medical device will be used only for this clinical trial; 
the receipt and use of the investigational medical device will be recorded 
completely and accurately and the records will be retained throughout the 
clinical trial.
4. To allow monitors and auditors authorized or designated by the sponsor 
as well as regulatory authorities to conduct monitoring, audit and 
inspection on the clinical trial.
5. To strictly perform the articles of clinical trial contract/agreement signed 
among parties.
I have already read the clinical trial protocol entirely, including the above 
statement, and I fully agree all the above contents.
Comments of sponsor  
Signature (stamp) 
MMDDYYYY
Comments of investigator
Signature
MMDDYYYY
Comments of the medical device study site
Signature (stamp)
MMDDYYYY

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Appendix I: References
1.
Cain, M.E., Atrial fibrillation--rhythm or rate control. N Engl J Med, 
2002. 347(23): p. 1822-3. 
2.
January, C.T., et al., 2014 AHA/ACC/HRS Guideline for the Management 
of Patients With 
Atrial Fibrillation: Executive SummaryA Report of the American College 
of Cardiology/American Heart Association Task Force on Practice 
Guidelines and the Heart Rhythm Society. Journal of the American 
College of Cardiology, 2014. 64(21): p. 2246-2280. 
3.
Calkins, H., et al., 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert 
consensus statement on catheter and surgical ablation of atrial 
fibrillation: Executive summary. J Arrhythm, 2017. 33(5): p. 369-409. 
4.
Kirchhof, P., et al., 2016 ESC Guidelines for the management of atrial 
fibrillation developed in collaboration with EACTS. Eur Heart J, 2016. 
37(38): p. 2893-2962. 
5.
January, C.T., et al., 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the 
Heart Rhythm Society in Collaboration With the Society of Thoracic 
Surgeons. Circulation, 2019. 140(2): p. e125-e151. 
6.
Jackman, W.M., et al., Catheter ablation of accessory atrioventricular 
pathways (Wolff- Parkinson-White syndrome) by radiofrequency current. 
N Engl J Med, 1991. 324(23): p. 1605- 11. 
7.
Jazayeri, M.R., et al., Selective transcatheter ablation of the fast and slow 
pathways using radiofrequency energy in patients with atrioventricular 
nodal reentrant tachycardia. Circulation, 1992. 85(4): p. 1318-28. 
8.
Wilber, D.J., et al., Comparison of antiarrhythmic drug therapy and 
radiofrequency catheter ablation in patients with paroxysmal atrial 
fibrillation: a randomized controlled trial. JAMA, 2010. 303(4): p. 333-
40. 
9.
Marrouche, N.F., et al., Circular mapping and ablation of the pulmonary 
vein for treatment of atrial fibrillation: impact of different catheter 
technologies. J Am Coll Cardiol, 2002. 40(3): p. 464-74. 
10. Oral, H., et al., Pulmonary vein isolation for paroxysmal and persistent 
atrial fibrillation. Circulation, 2002. 105(9): p. 1077-81. 
11. Pappone, C., et al., Atrial electroanatomic remodeling after 
circumferential radiofrequency pulmonary vein ablation: efficacy of an 
anatomic approach in a large cohort of patients with atrial fibrillation. 
Circulation, 2001. 104(21): p. 2539-44. 

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12. Haissaguerre, M., et al., Electrophysiological breakthroughs from the left 
atrium to the pulmonary veins. Circulation, 2000. 102(20): p. 2463-5. 
13. Nademanee, K. and B.A. Gidney, Pulmonary vein isolation without 
reconnection: a decade of trying. J Cardiovasc Electrophysiol, 2010. 
21(7): p. 738-40. 
14. Sauer, W.H., et al., Clinical predictors and outcomes associated with 
acute return of pulmonary vein conduction during pulmonary vein 
isolation for treatment of atrial fibrillation. Heart Rhythm, 2006. 3(9): p. 
1024-8. 
15. Cappato, R., et al., Prospective assessment of late conduction recurrence 
across radiofrequency lesions producing electrical disconnection at the 
pulmonary vein ostium in patients with atrial fibrillation. Circulation, 
2003. 108(13): p. 1599-604. 
16. Cappato, R., et al., Updated worldwide survey on the methods, efficacy, 
and safety of catheter ablation for human atrial fibrillation. Circ 
Arrhythm Electrophysiol, 2010. 3(1): p. 32-8. 
17. Arena, C.B., et al., High-frequency irreversible electroporation (H-FIRE) 
for non-thermal ablation without muscle contraction. Biomed Eng Online, 
2011. 10: p. 102. 
18. Gerstenfeld, E.P., Catheter Ablation of Atrial Fibrillation Using 
Electroporation: Back to the Future? JACC Clin Electrophysiol, 2018. 
4(8): p. 996-998. 
19. Lee, A. and E.P. Gerstenfeld, Electroporation-Application beyond 
pulmonary vein isolation? J Cardiovasc Electrophysiol, 2019. 30(9): p. 
1410-1411. 
20. Maor, E., et al., Pulsed electric fields for cardiac ablation and beyond: A 
state-of-the-art review. Heart Rhythm, 2019. 16(7): p. 1112-1120. 
21. Reddy, V.Y., et al., Pulsed Field Ablation for Pulmonary Vein Isolation in 
Atrial Fibrillation. J Am Coll Cardiol, 2019. 74(3): p. 315-326. 
22. Stewart, M.T., et al., Intracardiac pulsed field ablation: Proof of 
feasibility in a chronic porcine model. Heart Rhythm, 2019. 16(5): p. 754-
764. 
23. Sugrue, A., et al., Irreversible electroporation for catheter-based cardiac 
ablation: a systematic review of the preclinical experience. J Interv Card 
Electrophysiol, 2019. 55(3): p. 251-265. 
24. Caluori, G., et al., Irreversible electroporation-Let's keep it cool. J 
Cardiovasc Electrophysiol, 2018. 29(7): p. E12. 
25. Wojtaszczyk, A., et al., Irreversible electroporation ablation for atrial 
fibrillation. J Cardiovasc Electrophysiol, 2018. 29(4): p. 643-651. 
26. Frandsen, S.K., et al., Direct therapeutic applications of calcium 
electroporation to effectively induce tumor necrosis. Cancer Res, 2012. 

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72(6): p. 1336-41. 
27. Tracy, C.R., W. Kabbani, and J.A. Cadeddu, Irreversible electroporation 
(IRE): a novel method for renal tissue ablation. BJU Int, 2011. 107(12): 
p. 1982-7. 
28. Schoellnast, H., et al., The delayed effects of irreversible electroporation 
ablation on nerves. Eur Radiol, 2013. 23(2): p. 375-80. 
29. Lavee, J., et al., A novel nonthermal energy source for surgical epicardial 
atrial ablation: irreversible electroporation. Heart Surg Forum, 2007. 
10(2): p. E162-7. 
30. Neven, K., et al., Epicardial ablation: prevention of phrenic nerve 
damage by pericardial injection of saline and the use of a steerable 
sheath. Indian Pacing Electrophysiol J, 2014. 14(2): p. 87-93. 
31. Neven, K., et al., Myocardial lesion size after epicardial electroporation 
catheter ablation after subxiphoid puncture. Circ Arrhythm 
Electrophysiol, 2014. 7(4): p. 728-33. 
32. Neven, K., et al., Epicardial linear electroporation ablation and lesion 
size. Heart Rhythm, 2014. 11(8): p. 1465-70. 
33. Neven, K., et al., Safety and feasibility of closed chest epicardial catheter 
ablation using electroporation. Circ Arrhythm Electrophysiol, 2014. 7(5): 
p. 913-9. 
34. Wittkampf, F.H., et al., Myocardial lesion depth with circular 
electroporation ablation. Circ Arrhythm Electrophysiol, 2012. 5(3): p. 
581-6. 
35. Zager, Y., et al., Optimization of Irreversible Electroporation Protocols 
for In-vivo Myocardial Decellularization. PLoS One, 2016. 11(11): p. 
e0165475. 
36. DeSimone, C.V., S. Kapa, and S.J. Asirvatham, Electroporation: past and 
future of catheter ablation. Circ Arrhythm Electrophysiol, 2014. 7(4): p. 
573-5. 
37. van Driel, V.J., et al., Low vulnerability of the right phrenic nerve to 
electroporation ablation. Heart Rhythm, 2015. 12(8): p. 1838-44. 
38. Schoellnast, H., et al., Acute and subacute effects of irreversible 
electroporation on nerves: experimental study in a pig model. Radiology, 
2011. 260(2): p. 421-7. 
39. Tam, A.L., et al., Irreversible electroporation of the lumbar vertebrae in a 
porcine model: is there clinical-pathologic evidence of neural toxicity? 
Radiology, 2014. 272(3): p. 709-19. 
40. Li, W., et al., The effects of irreversible electroporation (IRE) on nerves. 
PLoS One, 2011. 6(4): p. e18831. 
41. Hong, J., et al., Cardiac ablation via electroporation. Conf Proc IEEE 
Eng Med Biol Soc, 2009. 2009: p. 3381-4. 

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Appendix II: ANTICIPATED ADVERSE EVENTS
(Acute) renal failure
Infection, systemic
(Aspiration) pneumonia
Inflammation
(Skin) laceration
Isolated ST segment elevation
(Vascular) bleeding
Liver toxicity
Acute Respiratory Distress Syndrome 
(ARDS) 
Local Hematoma/ecchymosis
Air embolism
Localized skin reaction
Allergic reaction to contrast media Allergic 
skin reaction 
Mitral Insufficiency
Allergic skin reaction
Myocardial infarction with or without ST elevation 
Altered Mental Status Confusion; Altered 
Level of Consciousness;
Nausea 
Anaphylactic shock
Neurological disorders (poor coordination) 
Anemia 
Neurological disorders (tremor) 
Anesthesia complications/reactions
Neuropraxia/Muscle contraction 
Anoxic or hypoxic encephalopathy
Palpitations 
Aortic Puncture
Papillary Muscle tear/injury
Apnea - sedation induced
Pericardial effusion resulting in tamponade 
Arrhythmia (new or worsening of pre-existing 
arrhythmia) 
Pericardial effusion without tamponade 
Asthmatic attack 
Pericarditis
Asymptomatic Cerebral Emboli 
Periesophageal vagal nerve injury
Atelectasis
Peripheral nerve injury
Atrial fibrillation
Phlebitis
Atrial Septal Defect (acquired) 
Phrenic nerve damage/injury
Atrio-Esophageal fistula 
Pleural effusion
Auditory Disorder 
Pneumothorax
AV fistula
Post- and perioperative pain
Back Pain
Post Procedural Hematuria
Bone disorder
Pseudoaneurysm
Bronchial fistula, Broncho-pericardium 
fistula 
Pulmonary edema
Cardiac arrest 
Pulmonary embolism
Cardiac pacemaker insertion or replacement 
Pulmonary hypertension
Cardiac perforation
Pulmonary toxicity, like acute pulmonary syndrome 
Cardiac Valve Rupture/Damage
Pulmonary vein dissection
Cardiogenic Shock 
Pulmonary vein stenosis
Cerebro-Vascular accident (CVA)/Stroke
Renal Artery Stenosis
Chest pain/discomfort
Respiratory arrest
Complete or incomplete heart block 
Respiratory depression 
Conduction block
Respiratory failure

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Coronary Artery Stenosis
Respiratory infection
Coronary artery thrombosis
Retinal Artery Embolism
Death
Retroperitoneal bleeding
Deep venous thrombosis
Rhabdomyolysis, including produced by body positio
n or propofol
Diaphragmatic paralysis
Sedation 
induced CO2 retention with lethargy and cholecystitis
Dislodgement/Malfunction of 
pacemaker/defibrilator leads
Seizure
Disseminated Intravascular Coagulation
Sepsis
Dizziness, presyncope, vertigo
Sinus bradycardia
Dysphagia
Sinus tachycardia
Dyspnea
Skin burn or necrosis
Endocarditis
Skin discoloration
Epigastric Distress
Skin edema
Epistaxis
Skin or soft tissue (radiation) injury/tear
Esophageal injury / perforation
Subclavian artery puncture
Expressive aphasia
Temperature elevation / Fever
Fatigue
Thrombocytopenia
Gastric hypomotility
Thromboembolism
Gastroesophageal reflux
Thrombosis
Gastrointestinal disorders
Thyroid disorders
Gastrointestinal diverticulosis
Toxic reaction
Gastroparesis
Transient extremity numbness
Headache
Transient Ischemic attack (TIA)
Heart failure (acute or chronic)
Urinary Retention Postoperative
Heart injury
Urinary tract injury or infection related to 
the urinary catheter
Heart valve insufficiency
Valvular damage/insufficiency
Hemoptysis
Vascular (access) dissection (including coronary 
arteries)
Hemorrhage
Vascular occlusion
Hemothorax
Vasovagal reactions
High/increased creatine phosphokinase (CPK)
Ventricular Fibrillation
Hypertension
Vessel damage/trauma
Hypervolemia
Vessel perforation
Hypotension
Vessel spasm (including coronary arteries)
Hypovolemia
Visual disturbance
Hypoxia
Worsening of pre-existing pulmonary disease
Increased phosphokinase level
Wound healing disturbance