Efficacy and Safety of Catheter Ablation for Atrial Fibrillation in Non-Fluoroscopic Cardiac Electrophysiology Lab: A Non-Inferior, Multi-Center, Prospective Randomized Controlled Trial
Phase: NA
Conditions: Atrial Fibrillation (AF)
Sponsor: Sir Run Run Shaw Hospital

Efficacy and Safety of Catheter Ablation for Atrial Fibrillation in Non-fluoroscopic 
Cardiac Electrophysiology Lab:  
A Non-Inferior, Multi-Center, Prospective Randomized Controlled Trial 
(NCT06719921) 
 
 
 
 
 
 
 
 
 
Protocol 
Version V3.0  
11/27/2025 
 
 
 
 
 
 

PROTOCOL SYNOPSIS 
Title 
Efficacy and Safety of Catheter Ablation for Atrial Fibrillation in 
Non-Fluoroscopic Cardiac Electrophysiology Lab: A Non-
Inferior, Multi-Center, Prospective Randomized Controlled 
Trial 
Purpose 
A randomized controlled trial to investigate whether catheter 
ablation in a non-fluoroscopy lab is non-inferior to catheter 
ablation in a conventional DSA lab in terms of efficacy and 
safety for treating atrial fibrillation (AF). 
Principal 
Investigato
r 
Dr. Jiang Chenyang 
Coordinati
ng Center 
Sir Run Run Shaw Hospital serves as the coordinating center 
for this clinical study with 16 EP centers participating. 
Trial 
Sponsor 
Biosense Webster 
Number of 
Subjects 
Up to 724 patients (procedures) will be enrolled over 1 year at 
16 EP centers.  
Inclusion 
Criteria 
Subjects must meet all the following inclusion criteria to be 
eligible for participation in this trial. 
• Age: ≥18 years 
• Patients diagnosed with paroxysmal AF or persistent AF 
≤1 year, who are referred for catheter ablation. 
• Patients referred for catheter ablation of AF (Pulmonary 
Vein Isolation) as a first-time intervention (no prior 
catheter ablation or surgical procedures for AF). 
• The patient is able and willing to provide written informed 
consent 

Exclusion 
Criteria 
Subjects who meet any of the following exclusion criteria are 
not eligible for enrollment. 
• Patients with contraindication to anticoagulation or to right 
or left sided cardiac catheterization 
• Patients scheduled for AF ablation procedures other than 
PVI and requiring X-ray fluoroscopy, such as VOM ablation, 
epicardial ablation, LAAO, CAG, etc. 
• Serious known concomitant disease with a life expectancy 
of < 1 year 
• MI, CABG, or PCI within the preceding 3 months 
• Left atrial diameter >55 mm 
• LVEF<30% 
• NYHA class III or IV 
• Awaiting cardiac transplantation or other cardiac surgery 
within 12 months. 
• History of a documented thromboembolic event within the 
past 6 weeks. 
•  Heart or vascular malformation that impedes catheter 
access or vascular puncture. 
• Current enrollment in an investigational study evaluating 
another device or drug. 
• Acute illness, active systemic infection, or sepsis. 
• Significant congenital anomaly or a medical problem that 
in the opinion of the investigator would preclude 
enrollment in this trial. 
 
Type 
A 
Non-Inferior, 
Multi-Center, 
Prospective 
Randomized 
Controlled Trial 
Design 
Sample Size Justification 

1) The sample size calculation will be based on the primary 
efficacy endpoint. 
Sample-size was calculated by non-inferiority log-rank test with 
1:1 design. The expected recurrence rate of AF is 30% for 
control group based on previous studies and our experience, 
and a hazard ratio of 1.3 was used for establish non-inferiority. 
Based on a power of 80% and an alpha of 0.05, proportion lost 
to follow up 5%, a sample size of 724 patients (362 for each 
group) was estimated. 
2）Safety endpoints will be collected in details and analyzed 
for comparison between the groups, but they will not be used 
to determine the sample size. 
 
 
 
 
 
 
 
 
 
 
 

Flowchart 
 
 
Ablation Procedure details (study and control group) 
The study will target AF catheter ablation procedures 
(Pulmonary Vein Isolation). After obtaining written informed 
consent, eligible patients will be randomized into one of the 
following two groups: 
Group 1: Non-Fluoroscopic Lab Group 
1. Ablation procedures will be performed in a 
catheterization lab equipped with non-fluoroscopic 3D 
electroanatomic mapping systems. 
2. No routine fluoroscopy will be used, except if deemed 
necessary for safety (e.g., complications or 
unexpected procedural difficulties), adhering to the 
ALARA principle. 
3. Pulmonary vein isolation (PVI) will be the sole ablation 
strategy, following the study protocol. 
 
Group 2: Fluoroscopic Lab Group (DSA Lab) 

1. Ablation procedures will be conducted in a 
fluoroscopy-guided catheterization lab using digital 
subtraction angiography (DSA) for catheter navigation. 
2. Radiation exposure will be recorded, and efforts will be 
made to minimize exposure by following the ALARA 
principle. 
3. Similar to Group 1, PVI will be the sole ablation 
strategy, as per protocol. 
Ablation strategy 
The primary ablation strategy for both groups will be pulmonary 
vein isolation (PVI). 
Other additional ablation, including but not limited to linear 
ablation, complex fractionated atrial electrogram (CFAE) 
ablation, or superior vena cava (SVC) isolation is not 
recommended unless necessitated by one of the following: 
 • Documented atrial flutter (AFL) or atrial tachycardia (AT) 
observed during the procedure, or 
 • Arrhythmias originating from the specific region requiring 
intervention.  
Energy Selection Principles 
Energy modality (RF or PF) will be selected by the investigator 
prior to randomization according to routine clinical practice, 
with a population-level expectation that the proportion of PFA 
among newly enrolled patients will progressively increase to 
approximately 50–60%, without influencing individual clinical 
decision-making. 
Recommendations  
1) The configuration of the Non-fluoroscopic Lab needs to 
be in accordance with the latest expert consensus 

recommendations (Jiang C, et al. Pacing Clin 
Electrophysiol. 2023 Sep;46(9):1035-1048). 
2) The use of ICE catheter is required for both groups. The 
application of ICE technology includes but is not limited 
to: visualizing the cardiac anatomy; guiding catheter 
placement, transeptal puncture (if necessary); 
constructing the geometry; monitoring intracardiac 
thrombus and cardiac effusion throughout the procedure. 
3) Magnetic mapping catheters (e.g. Lasso, PentaRay, or 
DECANAV) is recommended to create the cardiac 
geometry. 
4) A safe, rapid, and smooth plan for transfer to the DSA lab 
should be established if no mobile DSA equipment is 
available in the Non-fluoroscopic EP Lab. In the event of 
an emergency requiring the use of DSA, patient transfer 
should be completed in a minimal period to maximize 
patient safety.  
5) If deemed necessary, X-ray imaging may be utilized to 
guide catheter placement and monitor for potential 
complications. The use of X-ray must adhere to the As 
Low As Reasonably Achievable (ALARA) principle, 
ensuring radiation exposure is minimized while 
maintaining procedural safety and effectiveness. 
Duration  
April 22, 2025 – April 21, 2028, The study will be completed 
after the last enrolled subject has finished the 12-month follow-
up period. 
Objectives 
To evaluate the efficacy and safety of AF ablation without the 
use of fluoroscopy. 

Primary 
endpoint 
• 
The primary efficacy endpoint is treatment success at 12 
months without AAD, defined as freedom from recurrence 
of AF/AFL/AT lasting longer than 30 seconds. 
• 
The primary safety endpoint is a composite of the 
following prespecified procedure-related serious adverse 
events: death, stroke, transient ischemic attack, 
myocardial infarction, major vascular complication, or 
major bleeding within the first 7 days post procedure; 
development of a clinically significant pericardial effusion 
within 30 days; symptomatic pulmonary vein stenosis, 
atrial-esophageal fistula, or phrenic nerve injury within 3 
months. 
Secondary 
endpoint 
• 
The initial success of the procedure. 
• 
The proportion of intraoperative conversion to using X-ray. 
• 
Utilization of lead personal protective equipment (PPE) 
and wear time. 
• 
Quality-of-life for staff at the end of each procedure. 
• 
The proportion of patients with recurrence of AF/AFL/AT 
during the first 90 days post-ablation. 
• 
Early recurrence of atrial arrhythmias, defined as any 
AF/AFL/AT episode lasting >30 seconds occurring during 
the blanking period. 
• 
Late recurrence of atrial arrhythmias, defined as any 
documented AF/AFL/AT episode lasting >30 seconds 
occurring after the blanking period and up to 12 months. 
• 
Impact of early recurrence on late recurrence, 
assessed through survival analysis and multivariable 
adjustment to evaluate whether early recurrence predicts 

subsequent late recurrence. 
• 
AF burden, assessed by scheduled rhythm monitoring 
(e.g., 7-day Holter at 3, 6, 9, and 12 months), expressed 
as the proportion of time spent in AF during the monitoring 
period. 
• 
Incidence of peri-procedural complication. 
• 
Total procedure duration, ablation time. 
• 
Changes in quality-of-life 
Data 
Collection 
Three case report forms will be used to collect essential data 
Case Report Forms Include: 
1. Procedure Form 
• Patient-specific details 
• Procedural and ablation data, including de-identified 
Carto case backup data 
• Complications/adverse events during the procedure 
2. Complications/Adverse Events Form   
• Adverse events that occur after the patient leaves the 
procedure room through discharge  
• Adverse events from the discharge date through 7 
days post-procedure 
• Adverse events from day 8 through day 90 post-
procedure 
3. Effectiveness Form 
• 
For patients with atrial fibrillation, follow-up will be 
performed at 1 month, 2 months, 3 months, 6 months, 
9 months and 12 months post ablation. Patients' 
symptoms and 12-lead ECG will be recorded at each 
follow-up visit to assess recurrence, and a 7-day 

Holter monitor will be used at the 1-, 2-, 3-, 6-, 9-, and 
12-month visit.  
Pre and Post-Procedure Assessments to be documented on 
the CRFs include: 
• Baseline parameters including demographic data, 
TTE, CHADS2Vasc score and HAS-BLED score, OSA, 
AAD, OAC, interventions 
 
 
 

Investigator’s Statement 
I, the undersigned, have read and understand the trial protocol described 
herein.  I agree to perform and conduct the trial as described in the protocol 
and in accordance with applicable laws and regulations. I agree to maintain 
the confidentiality of all information received or developed in connection with 
this study. 
 
 
 
                                                                             
Investigator (Printed Name) 
 
___________________________ 
 
 
 
 
 
 
 
_________________  
Investigator                                     Signature Date                
 
 

1. Introduction 
1.1 What is the problem to be addressed? 
The problem to be addressed is whether the catheter ablation procedures 
for atrial fibrillation (AF) in a non-fluoroscopic electrophysiology (EP) lab have 
the same efficacy and safety to those procedures in a digital subtraction 
angiography (DSA) lab, especially when new techniques -like intracardiac 
echocardiography (ICE), contact force catheters, Pulse field ablation (PFA), 
etc.-could be used in both groups. 
 
1.1.1 Catheter ablation of atrial fibrillation and guidelines 
Catheter ablation has become a standard therapy for managing AF, 
particularly in patients with symptomatic paroxysmal or persistent AF who have 
failed medical therapy. Pulmonary vein isolation (PVI) remains the fundamental 
strategy for catheter ablation, and PVI is endorsed by guidelines from the 
European Society of Cardiology (ESC), American Heart Association (AHA), and 
Heart Rhythm Society (HRS) as the first-line approach for AF ablation1, 2. 
New innovations such as contact force-sensing catheters, 3D 
electroanatomic mapping systems, and ICE have improved catheter 
positioning, lesion precision, and procedural safety. In addition, Recent 
technological advancements have further optimized the safety and efficacy of 
AF ablation. PFA, a novel non-thermal ablation modality, uses electroporation 
to selectively ablate myocardial tissue while sparing adjacent structures such 
as the esophagus, phrenic nerve, and pulmonary veins. PFA has demonstrated 
potential for shorter procedure times and reduced risks of complications, 
offering a promising alternative to conventional thermal ablation techniques3-6. 
These advancements, combined with the established efficacy of PVI, are 
driving improvements in the outcomes and safety of catheter ablation 
procedures, addressing unmet needs in AF treatment, and broadening the 
scope of patients who can benefit from this therapy. 
 
1.1.2 Fluoroscopy related health risks and occupational injuries 
Historically, fluoroscopy has been the standard for guiding EP interventions; 
however, despite advancements that have reduced radiation exposure to safer 
levels7-10, the need for heavy personal protective equipment (PPE) remains a 
significant concern. Prolonged use of leaded PPE has been linked to chronic 
occupational injuries such as back, neck, and other joint pain, as well as more 
serious conditions like spinal disc herniation11, 12. These injuries are particularly 
concerning for healthcare providers who perform complex and lengthy 
procedures, potentially limiting their career longevity13, 14. 
 
1.1.3 Financial and environmental burdens of fluoroscopic labs 

Traditional EP labs pose substantial financial and environmental burdens. 
The setup of a new fluoroscopic lab, particularly one using DSA systems, 
involves significant initial investments—typically between 5 to 8 million yuan (¥) 
(687,400 to 1,100,000 dollars) per lab. Maintenance costs are also high, with 
annual fees reaching into the hundreds of thousands of yuan (¥) per lab. 
Moreover, fluoroscopic systems consume considerable energy, with each 
procedure requiring 60 to 70 kilowatt-hours of electricity to power X-ray 
machines and cooling systems. This not only drives up operational expenses 
but also contributes to increased carbon emissions. The sustainability of this 
approach is increasingly being questioned. 
 
1.1.4 Fluoro-less/-free practices for AF catheter ablation 
Non-fluoroscopic EP labs offer a feasible alternative, relying on advanced 
technologies such as three-dimensional (3D) mapping systems, contact-force 
catheters, and intracardiac echocardiography (ICE) to guide PE procedure 
without need for fluoroscopy. These systems not only reduce the need for heavy 
PPE and radiation exposure but also lower the financial and energy costs 
associated with traditional EP labs, making them more accessible and 
sustainable. Non-fluoroscopic EP labs offer a scalable and cost-effective 
solution, providing a more practical approach to addressing the growing 
demand for ablation therapies. Non-fluoroscopic EP labs, which eliminate the 
need for fluoroscopic imaging, have proven to be both feasible and safe15-20. 
The shift away from radiation-based guidance aligns with a growing focus on 
minimizing procedural risks and optimizing patient outcomes21, 22. While early 
studies suggest that non-fluoroscopic ablation techniques are feasible and 
effective23-25, comprehensive data on their clinical outcomes and long-term 
safety are still limited. there remains a critical need for large-scale, standardized 
assessments to validate these findings and support broader adoption of the 
technology26. Furthermore, recent studies have suggested that the 
characteristics of the blanking period following PFA may differ from those after 
conventional RF ablation, as early recurrences of atrial arrhythmias do not 
necessarily predict long-term failure, and the blanking period may be 
substantially shorter than the traditional 3-month duration.4, 27, 28 This highlights 
the need for large-scale studies to assess the real-world performance of non-
fluoroscopic ablation techniques. 
 
1.2 What are the principal research questions to be addressed? 
1.2.1 Study Question and Hypothesis 
We seek to assess the efficacy and safety of catheter ablation procedures 
for the treatment of AF, performed in a non-fluoroscopic EP lab. We hypothesize 
that the efficacy and safety outcomes of AF ablation in patients meeting the 
inclusion criteria of non-fluoroscopic EP lab will be non-inferior to those 

achieved in a conventional DSA lab under identical technical conditions. The 
findings of this study will not only validate the feasibility of non-fluoroscopic EP 
labs for AF ablation but also provide a foundation for their application to 
emerging ablation technologies, such as pulsed field ablation (PFA), which are 
anticipated to gain widespread adoption in the near future. 
 
1.2.2 Principal Research Questions 
(i) Efficacy: Do patients undergoing catheter ablation for AF in a non-
fluoroscopic EP lab achieve comparable success rates after one year or more 
of follow-up as those treated in a traditional DSA lab? 
(ii) Safety: Are severe complication rates in a non-fluoroscopic lab non-
inferior to those in a traditional DSA lab? 
(iii) Cost-effectiveness: Is a catheter ablation strategy in a non-
fluoroscopic EP lab cost-effective compared to traditional approaches? 
(iv) Target Population Selection: Given that not all patients are suitable 
for treatment in a non-fluoroscopic EP lab, can we identify specific patient 
characteristics at the point of entry to determine suitability for non-fluoroscopic 
procedures? 
 
2 
Description Of Study Device 
The following devices are included in the trial. New devices could be added 
to the list if they become available in the future. 
 
2.1 CARTO® 3 System 
The CARTO® 3 System is an imaging platform designed to support precise 
catheter navigation during cardiac procedures by generating real-time, three-
dimensional maps of the heart. Utilizing electromagnetic technology, it provides 
accurate location and orientation of catheters, contributing to enhanced 
procedural safety and efficiency. The system employs magnetic sensors 
embedded in the catheters, along with six patient patches, to calculate catheter 
positioning based on electromagnetic signals. Fast Anatomical Mapping (FAM) 
enables the rapid creation of detailed heart maps, streamlining the mapping 
process and improving workflow. 
 
2.2 SOUNDSTAR® Intracardiac Echocardiography (ICE) 
 
ICE catheters are 8 or 10 Fr steerable phased-array devices that provide 
a 90° ultrasound sector perpendicular to the catheter tip. The catheter tip can 
be deflected up to 160° in two planes (anteroposterior and lateral), enabling 
four-directional movement (anterior, posterior, left, and right) to generate 
diverse 2D imaging. 
The CARTOSOUND® Module is a new software module that integrating 
real-time 3D ultrasound imaging with the CARTO® 3 System, enhancing 

visualization of soft tissue during cardiac procedures. The SOUNDSTAR® 
catheter, equipped with a navigation sensor, allows its tip to be visualized on 
CARTO maps. This additional imaging capability allows for better catheter 
placement and monitoring of potential complications, such as blood clots or fluid 
accumulation. By improving visualization of critical structures, including the 
esophagus, the module helps minimize risks associated with catheter ablation 
procedures.  
 
2.3 Thermocool Smarttouch® &Thermocool Smarttouch® SF (ST&STSF) 
Catheter  
ST catheter is an irrigated-tip ablation, contact-force (CF)-sensing catheter 
indicated for cardiac mapping and ablation. The catheter contains a porous tip 
with 6 holes at the distal end. STSF catheter is a newer generation of the CF-
sensing and irrigated-tip ablation catheter indicated for cardiac mapping and 
ablation. The catheter contains a porous tip with 56 holes at the distal end. 
The increased number of holes at the distal tip improves the cooling effect at 
the catheter-tissue interface. This newer design also requires less fluid 
delivery through the distal tip which could reduce the risk of volume overload. 
When used in conjunction with the Carto®3 system, the catheter of both kinds 
is able to provide real-time CF data during catheter ablation. Due to the 
product's indication restrictions, we suggest to use ST/STSF catheter for 
persistent AF patients. 
SURPOINT is another new software module running with Carto 3 system. 
When used with ST and STSF catheter, SURPOINT is able to display AI value 
real-time on the Carto 3 system. The AI values can be used to guide the 
catheter ablation for durable lesion creation by ST and STSF catheter.  
 
2.4 QDOT catheter 
The Biosense Webster QDOT MICRO™ Catheter is a steerable multi-
electrode luminal catheter with a deflectable tip designed to facilitate 
electrophysiological mapping of the heart and to transmit radiofrequency (RF) 
current to the catheter tip electrode for ablation purposes. The catheter 
contains force-sensing technology that provides a real-time measurement of 
contact force between the catheter tip and the heart wall. The location sensor 
embedded in the tip section transmits location and contact force information to 
the CARTO® 3 System.  
The catheter incorporates six thermocouple temperature sensors in the tip 
section that can accurately monitor the catheter-tissue interface temperature 
and tip stability. 
 
2.5 Varipulse Platform 
The VaripulseTM platform from Biosense Webster is an innovative pulsed 
field ablation (PFA) system designed for treating atrial fibrillation. It uses a 
7.5Fr circular catheter with 10 electrodes, each with its own irrigation pore to 

improve cooling during ablation. The catheter is highly flexible, with 180° 
deflection in one direction and 90° in the other, making it easier to reach all 
pulmonary veins, including the more difficult-to-access right inferior pulmonary 
vein (RIPV). 
The PFA energy is delivered in a bipolar pattern between alternating 
electrodes (e.g., between electrodes 1 and 3), as well as between adjacent 
pairs (e.g., electrodes 1–2 and 2–3). The system applies 1800V of pulsed 
energy through brief microsecond-long pulses, lasting a total of 250 
microseconds per application. 
During the procedure, irrigation is maintained at a flow rate both at rest 
and during ablation, to ensure safe and effective procedure. 
 
3 
THE TRIAL 
3.1 Trial design  
This is a non-Inferior, Multi-Center, Prospective Randomized Controlled 
Trial ((1:1 randomization) conducted in China. The study aims to consecutively 
enroll up to 724 procedures over the course of one year at 10 EP centers with 
non-fluoroscopic labs accredited by the Chinese Heart Rhythm Society. The 
anticipated total study duration is 36 months, with a follow-up period of 12 
months for each participant. The study will be completed after the last enrolled 
subject has finished the 12-month follow-up period. 
Following informed consent, obtained either during the pre-procedure office 
visit or during hospitalization for the procedure, baseline data will be collected. 
This data will include patient demographics, medical history, prior treatments, 
and laboratory test results. 
The initial enrollment ratio between PFA and RF was projected to be evenly 
distributed at 50% each. Peri-procedural data, including procedural details, 
ablation strategies, acute success rates, VISITAG parameters, and any 
complications or adverse events, will be recorded up to the patient’s discharge. 
Post-discharge, participants will undergo follow-up evaluations at 1,2, 
3,6,9,12 months after the procedure. The follow-up schedule will remain 
unchanged even if a repeat ablation procedure is required. 
3.2 Study Rationale and Objective 
This randomized controlled trial aims to evaluate the efficacy, peri-
procedural safety, and clinical outcomes of catheter ablation performed in 
non-fluoroscopic EP labs compared to procedures in conventional DSA lab. 
With the rapid adoption of non-fluoroscopic EP labs in China, it is essential 
to assess their performance to ensure safe and effective care. We hypothesize 
that non-fluoroscopic procedures will demonstrate non-inferior safety and 
efficacy to fluoroscopy-guided ablations, while offering benefits such as 
reduced costs, minimized radiation exposure for physicians, and improved 
environmental sustainability. 

This study will provide evidence to guide clinical practice, improve patient 
care, and support the broader adoption of non-fluoroscopic EP technologies, 
enhancing access to advanced arrhythmia treatments and optimizing outcomes 
for patients with AF. 
3.3 Inclusion/exclusion criteria 
Inclusion criteria 
Subjects must meet all the following inclusion criteria to be eligible for 
participation in this trial. 
1) Age: ≥18 years 
2) Patients diagnosed with paroxysmal AF or persistent AF with a duration of 
1 year or less, who are referred for catheter ablation. 
3) Patients referred for catheter ablation as a first-time intervention (no prior 
catheter ablation or surgical procedures for AF). 
4) The patient is able and willing to provide written informed consent 
Exclusion criteria 
Subjects who meet any of the following exclusion criteria are not eligible 
for enrollment. 
1) Patients with contraindication to anticoagulation  
2) Patients with contraindication to right or left sided cardiac catheterization 
3) Patients scheduled for AF ablation procedures other than PVI and 
requiring X-ray fluoroscopy, such as VOM ablation, epicardial ablation, 
LAAO, CAG, etc 
4) Serious known concomitant disease with a life expectancy of < 1 year 
5) MI, CABG, or PCI within the preceding 3 months 
6) Left atrial diameter >55 mm 
7) LVEF<30% 
8) NYHA class III or IV 
9) Awaiting cardiac transplantation or other cardiac surgery within 12 
months. 
10) History of a documented thromboembolic event within the past 6 weeks. 
11) Heart or vascular malformation that impedes catheter access or vascular 
puncture. 
12) Current enrollment in an investigational study evaluating another device 
or drug. 
13) Acute illness, active systemic infection, or sepsis. 
14) Significant congenital anomaly or a medical problem that in the opinion of 
the investigator would preclude enrollment in this trial. 
 
3.4 Study Endpoints 
3.4.1 Primary endpoints 

The primary efficacy endpoint is freedom from any documented atrial 
arrhythmia, including AF, atrial tachycardia or atrial flutter episodes lasting 
longer than 30 seconds without antiarrhythmic drugs, for 12 months after the 
index ablation procedure, excluding a 3-month blanking period. The 
continuation or reinitiation of class I or class III antiarrhythmic drugs after the 3-
month post ablation blanking period, as well as electric cardioversion or 
catheter ablation for any atrial arrhythmias, are considered treatment failures 
for the primary end point. 
The primary safety endpoint is a composite of the following prespecified 
procedure-related serious adverse events: 
• 
Major vascular complication or major bleeding within the first 7 days post 
procedure. 
• 
Development of a clinically significant pericardial effusion. 
• 
Transient ischemic attack. 
• 
Stroke. 
• 
Myocardial infarction. 
• 
Severe pulmonary vein stenosis. 
• 
Atrial-esophageal fistula, or phrenic nerve injury within 3 months. 
• 
Death. 
3.4.2 Secondary endpoints 
• 
The acute success of the procedure.  
• 
The proportion of intraoperative conversion to using X-ray.  
• 
Utilization of lead personal protective equipment (PPE) and wear 
time.Well-being survey of staff. 
• 
The proportion of patients with recurrence of targeted arrhythmia during 
the first 90 days post-ablation.  
• 
Early recurrence of atrial arrhythmias, defined as any AF/AFL/AT episode 
lasting >30 seconds occurring during the blanking period. 
• 
Late recurrence of atrial arrhythmias, defined as any documented 
AF/AFL/AT episode lasting >30 seconds occurring after the blanking 
period and up to 12 months. 
• 
Impact of early recurrence on late recurrence, assessed through survival 
analysis and multivariable adjustment to evaluate whether early recurrence 
predicts subsequent late recurrence. 
• 
AF burden, assessed by scheduled rhythm monitoring (e.g., 7-day Holter 
at 3, 6, 9, and 12 months), expressed as the proportion of time spent in AF 
during the monitoring period. 
• 
Incidence of peri-procedural complication.  
• 
Total procedure duration, ablation time. 
• 
changes in quality-of-life (using the AF Effect on Quality of Life (AFQT) 
and the EuroQol Health-Related Quality-of-Life 3-Level (EQ-5D-3L)). 
 

 
3.5 Sample Size 
For efficacy as the primary endpoint, sample-size was calculated by non-
inferiority log-rank test with 1:1 design. The expected recurrence rate of AF is 
30% for control group based on previous studies and our experience, and a 
hazard ratio of 1.3 was used for establish non-inferiority. Based on a power of 
80% and an alpha of 0.05, proportion lost to follow up 5%, a sample size of 724 
patients (362 for each group) was estimated.  
Safety endpoints will still be collected in detail and analyzed for comparison 
between the groups, but they will not be used to determine the sample size. 
 
3.6 Study flowchart 
 
3.7 Planned trial interventions 
Ablation Procedure details (study and control group) 
The study will target AF catheter ablation procedures. After obtaining 
written informed consent, eligible patients will be randomized in a 1:1 fashion 
to one of the following two groups: 
Group 1: Non-Fluoroscopic Lab Group 
1. Ablation procedures will utilize ICE and 3D mapping systems for non-
fluoroscopic guidement. ICE is mandatory for real-time anatomical 
visualization.  
2. No routine fluoroscopy will be used, except if deemed necessary for 
safety (e.g., complications or unexpected procedural difficulties), 
adhering to the ALARA principle. 
3. Pulmonary vein isolation (PVI) will be the sole ablation strategy, 
following the study protocol. 

Group 2: Fluoroscopic Lab Group (DSA Lab) 
1. Ablation procedures will be conducted in a fluoroscopic lab. The use of 
ICE, 3D EP mapping systems, and other tools will follow the same 
recommendations as in the non-fluoroscopic lab group. 
2. Radiation exposure will be closely monitored and minimized in 
accordance with the ALARA (As Low As Reasonably Achievable) 
principles when necessary.  
3. Similar to Group 1, PVI will be the sole ablation strategy, as per 
protocol. 
Ablation strategy 
The primary ablation strategy for both groups will be pulmonary vein 
isolation (PVI). Additional ablation, including but not limited to linear ablation, 
complex fractionated atrial electrogram (CFAE) ablation, or superior vena 
cava (SVC) isolation will not be allowed unless required in the presence  of 
one the following: 
• 
Documented atrial flutter (AFL) or atrial tachycardia (AT) observed 
during the procedure, or 
• 
Arrhythmias originating from the specific region requiring intervention. 
 
Energy Selection Principles 
At the time of enrollment, the investigator will determine the planned 
ablation energy modality (radiofrequency [RF] or pulsed field [PF]) according to 
routine clinical practice, patient characteristics, procedural indications, device 
availability, and patient preference. The choice of energy modality is made prior 
to randomization, and the study protocol does not mandate or interfere with 
individual clinical decision-making. 
Given the increasing adoption and availability of pulsed field ablation (PFA) 
in current clinical practice, and in order to maintain the external validity of the 
study in the future era when PFA is expected to become the predominant 
ablation modality, the study adopts a population-level expectation for patients 
enrolled after the effective date of this protocol version: 
Without influencing individual clinical judgment, the cumulative proportion 
of PFA among subsequently enrolled patients is expected to progressively 
increase, with a target of achieving ≥50-60% of all newly enrolled cases. 
This expectation aims to optimize the overall energy composition of the 
study cohort to better reflect evolving clinical practice trends. It does not impose 
restrictions on individual patient-level energy selection and does not apply to 
participants enrolled prior to the implementation of this protocol amendment. 
 
Recommendations  
1) The configuration of the Non-fluoroscopic Lab needs to be in accordance 
with the latest expert consensus recommendations (Jiang C, et al. Pacing 
Clin Electrophysiol. 2023 Sep;46(9):1035-1048). 

2) The use of ICE catheter is required for both groups. The application of 
ICE technology includes but is not limited to: visualizing the cardiac 
anatomy; guiding catheter placement, transeptal puncture (if necessary); 
constructing the geometry; monitoring intracardiac thrombus and cardiac 
effusion throughout the procedure. 
3) Magnetic mapping catheters (e.g. Lasso, PentaRay, or DECANAV) is 
recommended to create the cardiac geometry. 
4) A safe, rapid, and smooth plan for transfer to the DSA lab should be 
established if no mobile DSA equipment is available in the Non-
fluoroscopic EP Lab. In the event of an emergency requiring the use of 
DSA, patient transfer should be completed in a minimum period to 
maximize patient safety.  
5) If deemed necessary, X-ray imaging may be utilized to guide catheter 
placement and monitor for potential complications. The use of X-ray must 
adhere to the As Low As Reasonably Achievable (ALARA) principle, 
ensuring radiation exposure is minimized while maintaining procedural 
safety and effectiveness. 
 
3.8 Clinical Equipoise 
3.8.1 Sample Size Justification  
Since complication rates are very low (estimated at 2-3% in the ICE group, 
based on literature29-32 and our prior experience), conducting a controlled 
study focusing on safety endpoints is not feasible. Additionally, our previous 
registry study has already provided supporting evidence on safety. In this study, 
while safety endpoints will still be collected in detail and compared between 
the two groups, they will not be used to calculate the sample size. Instead, the 
sample size calculation will be based on the primary efficacy endpoint. 
 
3.8.2 Ablation strategy  
PVI is well-established as the cornerstone strategy for AF ablation, 
particularly for paroxysmal AF, its effectiveness in persistent AF remains a 
subject of ongoing investigation. There is currently no robust clinical evidence 
to support that additional ablation strategies provide superior outcomes for all 
persistent AF patients33. Enhanced isolation of the vein of Marshall (EIVOM) 
has shown promise in improving outcomes for selected cases of persistent AF, 
particularly in addressing specific arrhythmogenic substrates. However, EIVOM 
is not universally applicable, as it often necessitates X-ray imaging and 
specialized techniques, which limit its use in fluoroscopy-free settings. 
To maintain clinical equipoise and ensure the feasibility of this randomized 
controlled trial, we have chosen to focus on patients with shorter durations of 
persistent AF. These patients are hypothesized to have a lower likelihood of 
requiring EIVOM or other advanced substrate modification strategies. This 

inclusion criterion allows us to evaluate the efficacy and safety of catheter 
ablation performed in non-fluoroscopic electrophysiology (EP) labs while 
minimizing the potential confounding effects of more complex ablation 
requirements. This approach ensures a balanced assessment of outcomes and 
aligns with the study's goal of evaluating PVI as the primary ablation strategy 
in a fluoroscopy-free context. 
 
4 
Data Collection 
An Electronic Data Capture (EDC) system will be employed for the 
collection and secure storage of study data. The system is equipped with 
several built-in data integrity features, including range checks, logic checks, 
and mandatory data field requirements to ensure the accuracy and 
completeness of entries. Each investigator will be granted a unique, 
password-protected login to access the database, and any alterations to 
subject data will be logged to maintain a clear audit trail. 
Primary data will be sourced from medical charts and procedural records, 
complemented by information gathered during structured interviews to assess 
quality of life (QoL) and other study-related metrics. Data collection will be 
managed by independent personnel who are not involved in the clinical care 
or procedural treatment of study subjects. Baseline, pre-procedural, and post-
procedural data will be extracted from the medical record, standard 
questionnaires, physical examinations, and laboratory tests conducted during 
office visits. Physicians performing the ablation procedures will be responsible 
for accurate and timely documentation of relevant procedural data in the 
medical record. 
Follow-up assessments will occur at the1-,2-, 3-,6-,9-,12-month mark and 
may be conducted through in-person interviews. However, in-person 
interviews are strongly recommended to ensure the most comprehensive 
evaluation. During these visits, subjects will complete standardized 
questionnaires, undergo physical examinations, and have laboratory tests 
performed as needed. A trained study coordinator will conduct the interviews, 
following a standardized protocol to ensure consistency across all sites. 
 
4.1 Data Acquisition 
Data will be collected prospectively at multiple time points, including 
baseline/pre-ablation, intra-procedural, prior to hospital discharge, and at the 
3-month follow-up post-index ablation. Patient demographic and clinical 
characteristics, procedural details, and concomitant medications will be 
recorded from medical charts. Information regarding lifestyle factors, 
medication adherence, adverse events, redo procedures, and quality of life 
(QoL) - general EQ-5D and the AF specific AFEQT assessment -will be 
obtained through either face-to-face interview, telephone consultations, or 
online platforms. 
At the1-, 2-, 3-, 6-, 9- and 12-month follow-up, arrhythmia recurrence will 

be assessed using a 12-lead ECG and a 7-day Holter monitor. In this study, 
the Kapatch dynamic electrocardiogram monitor (Zhejiang Medical Device 
Registration Certificate No.: 20202070050) will be also utilized for cardiac 
rhythm monitoring at the1-, 2-, 3-, 6-, 9-, and 12-month follow-up. 
 
4.2 Procedure of Data Collection  
At each site, all subjects that meet all inclusion criteria and do not have 
any exclusion criteria will be enrolled non-selectively.  
All subjects meeting the enrollment eligibility criteria will be recorded in a 
patient log. Patient logs will be kept in individual participant hospitals and do 
not need to be submitted to the Coordinating Center. The enrolled subjects 
will be compared with those who meet the inclusion/exclusion criteria but are 
not enrolled in the study to assess the enrollment selection bias. Only 
subjects who have signed the informed consent are enrolled and the follow-up 
data including the rhythm monitoring data collected according to the study 
protocol. For those who are eligible but fail to enroll due to unwillingness to 
sign the informed consent or due to other reasons, only baseline 
characteristics data, procedure data and in hospital stay outcomes (severe 
procedure related complications, prolonged hospital stay) will be collected. An 
informed consent waiver is required from EC/IRB for each participating site. 
The data to be collected at each time point is listed in Table 1. 
The accuracy of data collection will be validated by comparing with the source 
data. At least 10% of each data variable will be randomly selected for validation 
by EDC system. Demographical data will be 100% SDV, and the remaining 
data variables will be selected for validation at various ratios depending on the 
criticality of the variable. SDV randomization ratio will be dynamically reset by 
error rate of each site and each variable. 
 
Table 1. Data collected at different time points 
  
Basel
ine/Pr
e-
Ablati
on 
 
Ablati
on 
and 
Pre-
Disch
arge 
1M 
[Days
30±7] 
2M 
[Days
60±7] 
3M 
[Days 
90±
14] 
6M 
[Days 
180±
30] 
9M 
[Days  
270±
30] 
12M 
[Days 
365±
45] 
Informed Consent 
√ 
 
 
 
 
 
 
 
Face to Face 
interview/Tele-
interview 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Questionnaire 
√ 
 
 
√ 
√ 
 
√ 
Socio-demographic 
√ 
 
 
 
 
 
 
 
Medical history  
√ 
 
 
 
 
 
 
 

Smoking, alcohol 
consumption  
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
New onset medical 
conditions 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Concomitant 
Medications 
√ 
（√） 
（√） 
（√） 
（√） 
（√） 
√ 
Transthoracic 
echocardiography 
（√） 
（√） 
（√） 
（√） 
（√） 
（√） 
（√） 
（√） 
Neuroimaging of 
the cranium 
√ 
√ 
（√） 
（√） 
（√） 
（√） 
（√） 
（√） 
Laboratory 
investigations 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
EQ-5D 
√ 
 
 
 
√ 
√ 
 
√ 
AFEQT (for 
AF/AFL) 
√ 
 
 
√ 
√ 
 
√ 
Physical 
examination 
√ 
（√） 
（√） 
（√） 
（√） 
（√） 
（√） 
（√） 
Ablation Record  
 
√ 
 
 
 
 
 
 
ECG record 
(Holter) 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Re-ablation and 
ablation sites 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
SAEs 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Cardiovascular 
related emergency 
visit and 
hospitalization  
 
 
√ 
√ 
√ 
√ 
√ 
√ 
 
4.3 Data Elements  
The following data elements will be collected in three case report forms 
and a site questionnaire.  
Pre-procedure data 
The following pre-procedure data will be collected in one of the case report 
forms. 
Demographics 
age, sex, education background, medical 
insurance information, etc 
Medical history  
medical history (congestive heart failure, 
hypertension, coronary heart disease, 
diabetes, stroke/TIA history, systemic arterial 
embolization, bleeding history, CHADSVASC 
for AF, arrhythmia history) and heart surgery 
history 
Physical examination  
blood pressure, heart rate and heart 
rhythm, and body weight and height 

Laboratory test  
 CBC, Electrolytes, glucose, serum 
cholesterol, creatinine, INR 
Echocardiogram  
left ventricular ejection fraction (LVEF), left 
atrium diameter and volume, presence and 
severity of mitral and tricuspid regurgitation, 
LAA detection methods (CT/TEE/ICE), 
whether there is spontaneous echo contrast in 
TEE examination 
Concomitant 
Medications 
blood pressure lowering drugs, diabetic 
medications, lipid lowering drugs, continuous 
or interrupted anticoagulants, AADs 
Quality of life (QoL) 
general EQ-5D and the AF specific AFEQT 
assessment 
Procedural Data 
The table below lists the information documented during AF ablation and 
pre-discharge hospital stay. These data will be collected in another case 
report form. 
Cardiac 
arrhythmia 
□paroxysmal AF 
□persistent AF ≤1year 
□Others,                                    
Anesthesia 
or sedation 
level 
minimal sedation, conscious sedation, deep sedation or 
general anesthesia 
Ablation 
and mapping 
catheters  
list the catheters 
Procedural 
and ablation 
data 
total procedure time, Mapping time and points, RF 
application time 
Ablation 
strategies : 
Ablation sites 
in addition to 
PVI including 
the AI value 
per ablation 
line 
Circumferential pulmonary vein isolation (CPVI) 
Additional: 
Line ablation: LA roof line/LA anterior line/LA posterior 
line/CTI/Mitral isthmus/SVC 
CFAE/Rotors/Substrate modification 
Others 
 
Acute 
success 
□Yes   □No, reason:                           
VISITAG® 
parameters 
number of tags, CF, power and energy deliver time per 
lesion, AI value per application and per segment, 
impedance drop 
Data will be collected in the CARTO® 3 Navigation 

System during the ablation procedures for generation of left 
atrium ablation maps in accordance with predefined 
segments of anterior wall, ridge, posterior wall, roof and 
inferior area 
VISITAG® parameters source database should be 
exported from Carto system and saved on One Drive. 
Checklist will be provided to record the participants’ ID, file 
ID and uploading information.  
 
ACT 
Max ACT during ablation                 
Pre-
discharge 
data 
• Supine time after ablation  
• Concomitant medications (anticoagulation, AAD, BP-
lowering drugs, lipid-lowering drugs, and antidiabetic 
drugs) 
• Postprocedural complications/adverse events 
(device/procedure-related and any SAEs) 
• Length of stay in hospital 
 
Subject Follow-Up Data 
Subject follow-up data are collected in the effectiveness and safety data 
form and include items listed in the table below: 
Patient information 
weight, blood pressure, QOL, EHRA score, 
life style,  
Concomitant 
medications 
anticoagulation, AAD, blood pressure-
lowering drugs, lipid-lowering drugs, and 
antidiabetic drugs 
Documented 
AF/AFL/AT recurrence 
12-lead ECG/7-day Holter, AF burden in the 
holter 
Repeat procedure 
Re-ablation and ablation sites 
Emergency or re-
hospitalization 
Cardiovascular related emergency visit and 
re-hospitalization due to arrhythmia recurrence 
or procedure-related reasons 
New onset medical 
conditions 
hypertension, diabetes, major bleeding, renal 
dysfunction, etc. 
Serious procedure or 
device related adverse 
events 
List (Appendix A) 
 
5. Trial/Repository Administration 
The trial will be conducted in compliance with this protocol, and according 
to ISO 14155: 2011, Clinical Investigation of Medical Devices for Human 
Subjects, and the International Conference on Harmonization (ICH) 
Harmonized Tripartite Guideline of Good Clinical Practice (E6). 
 

5.1 Institutional Review Board/Ethics Committee 
This protocol must be reviewed and approved by the appropriate IRB/EC 
where the trial is to be conducted before enrollment of subjects. The IRB/EC 
must approve in writing any changes to the protocol that affect the rights, 
safety, or welfare of the subjects, or may adversely affect the validity of the 
trial. 
A signed copy of the IRB/EC Approval Form and a signed copy of the 
IRB/EC approval letter addressed to the investigator must be submitted to the 
Coordinating Center certifying registry approval before subject enrollment. 
Investigators are responsible for submitting and obtaining initial and 
continuing review of the trial by their IRB/EC. 
 
5.2 Responsibilities 
The investigator is responsible for ensuring the trial is conducted in 
accordance with the procedures and evaluations described in this protocol 
(see Investigator Signature Page at the beginning of this protocol). 
Deviations from the protocol shall not be made without discussion with the 
Coordinating Center. Changes to the protocol may be made only when a 
written protocol amendment provided by the sponsor has been signed by the 
investigator and approved by the IRB/EC and applicable regulatory agencies 
in accordance with local requirements. 
 
5.3 Restrictions 
Only staff listed in the delegation can log in the internet-based data 
management system with an authorized account and the unique individual 
password. 
 
5.4 Confidentiality 
 Authentication technology is adopted to meet demands like identity 
authentication and non-repudiation. Sensitive data will be stored via a data 
encryption technology and cross-domain data transfer will be encrypted. The 
present trial will sign a confidentiality agreement with the staff who manage 
and operate the important information. Information manager should not modify 
or delete the existing information without authorization. Unrelated people are 
restricted to access to the clinical research EDC system. 
Data managers will daily check all the uploaded data case by case, and if 
there’s a question, he/she shall raise it and send a reminder to the 
investigator. Data managers are served by experienced physicians from 
HHRC. All questions will be listed with the content, questioner, proposed date 
and resolved date recorded in detail. 
The study team will retain all study records required by the HHRC and by 
the applicable regulatory bodies in a secure and safe facility for a minimum 
period of 15 years. 
The Sir Run Run Shaw Hospital Clinical Trials Centre will function as the 

coordinating centre for all aspects of this trial. The Data Management 
Coordinating Centre will oversee the intra-study data sharing process, with 
input from the Data Management Subcommittee. 
All Principal Investigators will be given access to the cleaned data sets. 
Project data sets will be housed on the Project Web Database and/or the file 
transfer protocol site created for the study, and all data sets will be password 
protected. Project Principal Investigators will have direct access to their own 
site’s data sets and will have access to other sites data by request. To ensure 
confidentiality, data dispersed to project team members will be blinded of any 
identifying participant information. 
 
5.5 Private Health Information (PHI)  
Subjects will be identified on the case report form by number codes only, 
using the criteria provided by the coordinating center. Local IRB approval is 
required for each participating site.     
All information and data sent to the Coordinating Center concerning 
subjects or their participation in this trial will be considered confidential. Only 
authorized Coordinating Center personnel or designee, or local government 
authorities acting in their official capacities will have access to these 
confidential files. All data used in the analysis and reporting of this evaluation 
will be without identifiable reference to the subject. 
 
6. Data Collection and Management 
The Coordinating Center will perform all data management activities for 
this trial. These activities include development and validation of a clinical 
database into which all trial data will be entered. The Coordinating Center will 
be responsible for ensuring overall integrity of the data and database. Data 
will be stored on a secure cloud server. Only authorized study person will be 
able to access EDC. ID and password will be used to protect data security. 
 
6.1 Data Collection 
Case Report Forms (CRF) will be used to collect all subject data for the 
trial. The CRF will be developed to capture the information outlined in this 
protocol. Data collected on these CRFs will be entered to an Electronic Data 
Capture (EDC) System by individuals at the Coordinating Center and 
analyzed by the trial Sponsor as defined in the trial protocol. 
 
6.2 Data Reporting 
The site investigator, or a designated individual, is responsible for ensuring 
that trial data are properly recorded on each subject’s CRF and related 
documents. Completed CRFs will be reviewed by Coordinating Center 
personnel throughout the trial. 
All CRFs should be completed and submitted to the Coordinating Center 
using the guidelines set for by the Coordinating Center. For AE reporting, 

refer to the Adverse Event Reporting Requirements and timelines within this 
trial protocol. 
 
6.3 Source Documentation 
Source documents will serve as the basis for validation of data entered 
into the EDC system. Source documents may include subject medical 
records, hospital charts, clinical charts, the investigator’s subject registry files, 
admissions and discharge summaries, as well as the results of diagnostic 
tests such as X-rays, laboratory tests, and electrocardiograms. 
If no standard hospital or office document exists to capture information that 
may be unique to this trial, a worksheet may be developed to record this 
information, which shall be signed by the PI at the given site and serve as the 
source document for unique trial data. 
Electronic subject records will be considered source documents on the 
condition that the hospital’s database is a validated system. If this is not the 
case, electronic records will have to be printed and added to the subject’s 
paper file.  
Regulations require that investigators maintain information in the subject’s 
medical records, which corroborate data collected on the CRF. 
Variables collected will be validated with source data. Demographical data 
will be 100% SDV, and the rest of data to be set up different randomization 
ratio, based on the variable priority. At least 10% of transferred data will be 
randomly selected by EDC system. 
If there are no discrepancies, then monitor does not have to SDV anymore 
data for that visit. If there are discrepancies, then the amount to SDV will 
increase by 10% and will continue to increase until 50%. If discrepancies are 
still found after 50%, then all data will have to be SDV. The Site Monitor may 
also check the compliance of the site with the protocol and to detect issues 
that may be difficult to assess from remote monitoring alone. 
The Project Manager – he/she will be responsible for the day to day 
running of the study including liaising with the individual study sites and study 
research co-coordinators. This individual will supervise the activities of the 
Study Nurses with respect to patient eligibility, data accumulation and 
transmission, and patient follow-up. 
There will also be a separate and independent data safety and monitoring 
board (DSMB). The DSMB will consist of three people. All members of the 
DSMB have extensive clinical trials experience and were invited on the basis 
of their expertise and independence. The DSMB will monitor the study safety 
data on an ongoing basis. 
 
6.4 Missing Data Handling 
This study is a real-world study, and all the data will be recorded based on 
the medical routine of the hospital and the actual completed status of the 
subjects. If there are missing data, compliance with medical routine is not 

considered as a protocol deviation.  
6.5 Energy Composition Target and Monitoring 
Each participating center is required to maintain complete documentation 
of the ablation energy modality selected for all enrolled cases. Following the 
effective date of this protocol version, the Coordinating Center will periodically 
review and summarize the energy composition of newly enrolled patients to 
assess whether the overall distribution aligns with the anticipated study 
trajectory. 
To ensure that the study cohort adequately reflects the increasing clinical 
adoption of PFA and maintains relevance in a future PFA-dominant treatment 
environment, the study establishes the following population-level target for the 
overall energy composition during the study period:  
Across the entire enrollment period, the cumulative proportion of 
PFA cases is expected, in principle, to reach at least 50-60% of all 
enrolled subjects. 
This target is intended to optimize the cohort’s energy structure at the 
population level and enhance the interpretability and external validity of study 
results in the context of evolving ablation practice. It does not impose 
restrictions on the energy selection for individual cases and does not 
constitute a mandatory requirement for any participating center or 
investigator. This monitoring process is implemented solely to support study 
quality control and consistency in data interpretation. 
 
7. Adverse Event Evaluation, Record and Report 
7.1 Adverse event 
Adverse events (AE) mean any untoward medical occurrence during 
clinical trials, whether related to catheter ablation. An AE can be any adverse 
or unexpected sign associated with catheter ablation in time, a symptom 
reported by a subject, or any disease, whether or not it has a causal 
relationship with catheter ablation.  
 
7.2 Serious adverse events 
Serious adverse event (SAE) refers to an event or reaction that, in the 
view of either the investigator or sponsor, results in any of the following 
outcomes: death, a life-threatening adverse event, in-patient hospitalization or 
prolongation of existing hospitalization, a persistent or significant incapacity or 
substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly or birth defect.  
 
7.3 Suspected Unexpected Serious Adverse Reactions (SUSARs) 
SUSARS refer an adverse event that occurs in a clinical trial subject, 
which is assessed by the sponsor and or study investigator as being 
unexpected, serious and as having a reasonable possibility of a causal 
relationship with the ablation.  

An independent Advisory Committee comprising clinical 
electrophysiologists, device experts, and procedural workflow specialists will 
provide non-binding recommendations throughout the course of the trial. This 
committee will offer guidance on clinical protocol development, training 
procedures, data interpretation, and integration of new technologies as they 
become available. The Advisory Committee does not have access to 
unblinded safety data but will work in coordination with the Sponsor and 
DSMB to ensure the trial remains aligned with current clinical practice 
standards and technological advancements. 
 
7.4 Device defects  
Device defects refer to unreasonable risks that may likely cause or 
contribute to a death or serious injury under common practice, such as label 
errors, quality problems, malfunction, etc. 
 
7.5 Collect and report serious adverse events, device defects, and 
unexpected serious adverse events 
7.5.1 Collection time 
AE evaluation will be conducted from the signing of informed consent to 
the end of this trial. 
 
7.5.2 SAE Reporting 
After initial receipt of SAEs, the investigator should provide proper 
treatment and write to the relative facilities and sponsor immediately.  
The investigator is responsible for continuing to follow all SAE reports 
(whether related to study drug) until resolution or until the event is considered 
chronic and/or stable by the investigator and/or other physician who has the 
responsibility for the patient’s medical care. Follow-up SAE reports will be 
reported according to the same timelines as initial reports as soon as new 
significant information becomes available.  
For SAE or suspected SAE-related device defects, the sponsor should 
report to the CFDA and the health authority at the same level and notice other 
sites in this trial. Study sites should report to the ethnic committee by the 
clinical trial management department. 
 
7.5.3 Device defects Reporting 
If any issues with the study device arise, including suspected or confirmed 
malfunctions related to quality, labeling, durability, reliability, or safety, please 
contact the designated Johnson & Johnson representative immediately. 
 
7.5.4 SUSARs Reporting 
Suspected Unexpected Serious Adverse Reactions [SUSARs] will undergo 
expedited reporting to relevant regulatory authorities (e.g., research ethics 
committees, National Medical Products Administration, and National Health 

Commission of the People’s Republic of China). Investigators must report all 
SUSARs to sponsor as soon as possible and 24h of learning of the event. 
These SUSARs will be centrally reviewed and reported by the sponsor as 
soon as possible:  
For fatal or life-threatening SUSARs, sponsor must report as soon as 
possible and within 7 days of learning of the events. Active follow-up must be 
completed within the following 8 days (The first day of learning of the event is 
considered 0 day).   
For fatal or life-threatening SUSARs, sponsor must report as soon as 
possible and within 15 days of learning of the events. 
8. Statistical analysis  
Continuous variables are expressed as mean ± SD if normally distributed or 
median (interquartile range [IQR]) if not normally distributed. Intergroup 
differences will be compared by student’s t-test (normally distributed data with 
equal variance) or Mann-Whitney U test (failed either normality or equal 
variance test). Categorical variables will be presented as percentages and 
compared by using the Chi-square test or Fisher’s exact test. The Kaplan-Meier 
method will be used to describe event-free rates over time. The statistical 
significance for all tests will be accepted at P< 0.05. 
 
8.1 Sub-analyses 
8.1.1 Sub-analysis 1: Comparison of PFA VS RFA 
This sub-analysis will compare the 12-month efficacy and safety of PFA and 
RFA using data collected in the main study. 
All analyses will be performed post-hoc within the predefined data 
framework of the primary trial; no additional interventions, visits, or consent are 
required. 
 
8.1.2 Sub-analysis 2: Impact of blanking period definitions following 
PFA 
This sub-analysis will explore the effect of different blanking period 
definitions (1-month, 2-month vs 3-month) on arrhythmia-free success rates 
after PFA, using the same dataset and follow-up schedule as the main study. 
It is an exploratory analytical component of the main trial and does not 
involve separate randomization or data collection. 
 
8.1.3 Sub-analysis 3: Impact of AF duration and symptom/diagnosis-
to-ablation interval on ablation success 
This sub-analysis will explore whether different time definitions influence the 
interpretation of 12-month ablation success. Two analytical models will be 
applied using the main trial dataset without additional interventions or visits: 
• 
Model A (documented AF duration model): Patients will be stratified 
by AF type (paroxysmal vs. persistent ≤1 year) and analyzed according 
to documented AF duration based on the first recorded AF episode. 

• 
Model B (symptom/diagnosis-to-ablation interval model): Patients 
will be stratified according to the interval from initial symptom onset or 
first AF diagnosis—whichever occurs earlier—to the ablation procedure, 
with categories defined by the actual distribution of the study population. 
This exploratory sub-analysis compares analytical approaches only; it does 
not modify clinical management, affect randomization, or add data collection 
requirements. 
 
9. Consenting Process 
Local IRB approval must be obtained before patient enrollment. Informed 
consent form signed and dated by both investigator and subject must be 
obtained from all subjects prior to exporting the data from the hospital database 
for this study. Any modifications to the Patient Informed Consent Form must be 
approved by the Ethics Committee (EC). The copy of the Patient Informed 
Consent Form approved by EC, along with the copies of consent forms signed 
by every subject, must be maintained by every investigator in a designated 
clinical trial master file. A signed copy of the consent form must be given to each 
subject. It is the investigator’s responsibility to ensure that the informed consent 
process is performed in accordance with good clinical practices (GCP). 
 
10. Plans For Publication 
We plan to submit primary safety and efficacy data for publication in a peer-
reviewed journal. Additional publication plans will be discussed in consultation 
with the study PI and local PIs during independent publication planning 
meetings. Participating investigators are encouraged to propose publication 
ideas, which will be reviewed for suitability by the steering committee in these 
planning meetings. 
Publication of trial results will be coordinated independently. Biosense 
Webster, Inc. will not interfere with the trial's conduct, data management, or 
authorship decisions. Authorship and publication processes will be led by the 
Trial Principal Investigator to uphold scientific integrity and objectivity. 
 
 
 

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Appendix  
Appendix A.  Anticipated Adverse Events 
 
1. Acute Respiratory Distress Syndrome 
(ARDS) 
35. Laceration 
2. Air embolism 
36. Leakage of air or blood into the lungs or 
other organs due to perforation 
3. Allergic reaction 
37. Local hematoma/ecchymosis 
4. Anemia 
38. Mobile strands in the inferior vena cava 
5. Anesthesia reaction 
39. Myocardial infarction 
6.  Arrhythmias 
40. Obstruction or perforation or damage to the 
vascular system 
7. Atelectasis 
41. Pericardial effusion 
8. Atrio-Esophageal Fistula 
42. Pericarditis 
9. Atypical flutter 
43. Phrenic nerve damage 
10. AV fistula 
44. Pleural effusion 
11. Cardiac perforation/tamponade 
45. Pneumonia 
12. Cardiac Thromboembolism 
46. Pneumothorax 
13. Cerebrovascular accident (CVA) 
47. Pseudoaneurysm 
14. Chest pain/discomfort 
48. Pulmonary edema 
15. Complete heart block, temporary or 
permanent 
49. Pulmonary embolism 
16. 
Component 
damage 
to 
ICD 
or 
pacemaker 
50. Renal Failure 
17. Congestive heart failure 
51. Respiratory depression/failure 
18. Coronary artery dissection 
52. Retroperitoneal hematoma 
19.Coronary artery spasm 
53. Rhabdomyolysis, including that produced 
by body position or propofol 
20. Death 
54. Seizure 
21. Dislodgement of ICD or permanent 
pacing leads 
55. Shortness of Breath 
22.  Endocarditis 
56. Skin burns due to cardioversion, tape, etc. 
23. 
Exacerbation 
of 
pre-existing 
atrial 
fibrillation, or other arrhythmia 
57. Syncope/Dizziness 
24. Expressive aphasia 
58. Temperature elevation 
25. Hair loss due to anesthesia 
59. Thromboembolism 
26. Heart failure 
60. Transient ischemic attack (TIA) 
27. Hematuria 
61. Unintended complete/incomplete AV, sinus 
node or other heart block or damage 
28. Hemorrhage 
62. Urinary tract injury or infection related to 
the urinary catheter 
29. Hemothorax 
63. Valvular damage/insufficiency 
30. Hypertension/Hypotension 
64. Vasovagal reactions 

31. Increase in frequency or duration of 
episodes of typical atrial flutter 
65. Volume overload 
32. Increased phosphokinase level 
66. Worsening obstructive, restrictive, or other 
form of pulmonary disease 
33. Infection, localized or systemic 
67. X-ray radiation injury of skin, muscle or 
organ 
34. Injury to skin, muscle, connective tissue 
due to body position, electrical cardioversion, 
etc. 
 
 
 
 

Appendix B.  Definition of related hospitalization 
 
Heart failure 
Hospitalization event that meets ALL of the following criteria: 
1. The patient was admitted to the hospital with a primary 
diagnosis of HF as the cause for hospitalization. 
2. The patient’s length of stay in hospital extended for at least 24 
hours (or a change in calendar date if the hospital admission and 
discharge times are unavailable). 
3. Diagnosis of HF by at least 1 of each of the following 3 criteria: 
symptom, sign, and medication (specifically for the treatment of 
worsening 
heart 
failure)/supportive 
measures/objective 
assessments. 
Arrhythmia 
When a patient was hospitalized for elective or urgent diagnosis or 
treatment of bradyarrhythmias, atrial, or ventricular rhythm 
disorders of the heart. 
Transient 
ischemic 
attack 
and 
stroke 
When a patient was hospitalized for elective or urgent diagnosis or 
treatment of TIA or stroke. 
TIA was defined as a transient episode of focal neurological 
dysfunction lasting for <24 hours caused by brain, spinal cord, or 
retinal ischemia, without acute infarction. 
Stroke was defined as an acute episode of focal or global 
neurological dysfunction caused by brain, spinal cord, or retinal 
vascular injury as a result of hemorrhage or infarction.  
Myocardial 
infarction 
When there was evidence of myocardial necrosis in a clinical 
setting consistent with myocardial ischemia, and required the 
combination of: 
1. Evidence of myocardial necrosis (either a typical rise and fall in 
cardiac biomarkers or postmortem pathological findings); and 
2. Supporting information derived from the clinical presentation, 
electrocardiographic changes, or results of myocardial or coronary 
artery imaging. 
Other 
CV 
cause 
A hospitalization not included in the above categories but with a 
specific, known cause (including but not limited to: hospitalization 
for 
unstable 
angina, 
pulmonary 
embolism 
or 
peripheral 
arterial/vascular disease, peripheral emboli, venous thrombosis, or 
other vascular reasons or complications). 
Hospitalization for end point adjudication was defined as a nonelective 
admission to an acute care setting for medical therapy that results in at least a 
24-hour stay (or a date change if the time of admission/discharge is not 
available).  
 
 
 

Appendix C.  Quality of life scale (EQ-5D-5L)  
Patients will be asked to grade their Quality of Life, since the start of the study, 
using EQ-5D (The EuroQol Group. Health Policy 1990 December; 16(3):199-
208).   
  
 
Tick one 
answer in 
each section 
MOBILITY  
I have no problems in walking about   
I have slight problems in walking 
I have moderate problems in walking 
I have severe problems in walking 
I am unable to walk about  
SELF-CARE  
I have no problems washing or dressing 
I have slight problems washing or dressing 
I have moderate problems washing or dressing 
I have severe problems washing or dressing 
I am unable to wash or dress myself   
USUAL ACTIVITIES (e.g. work, study, housework family or 
leisure activities)
I have no problems with performing my usual 
I have slight problems with performing my usual 
I have moderate problems with performing my usual 
I have severe problems with performing my usual 
I am unable to perform my usual 
PAIN / DISCOMFORT  
I have no pain or discomfort   
I have slight pain or discomfort   
I 
have 
moderate 
pain 
or 
I 
have 
severe 
pain 
or 
I have extreme pain or discomfort   
ANXIETY 
/ 
I am not anxious or depressed   
I am slightly anxious or depressed   
I 
am 
moderately 
anxious 
or 
I 
am 
severely 
anxious 
or 
I 
am 
extremely 
anxious 
or 
Patients will also be asked to grade their state of health on the visual analogue 
scale.   
“To help people say how good or bad their state of health has been on average 
since starting the study, we have drawn a scale (rather like a thermometer) 
on which the best state you can imagine is marked 100 and the worst state you 
can imagine is marked 0.  
We would like you to indicate on this scale how good or bad your health has 

been on average since starting the study in your opinion.  Please do this by 
drawing a line on the scale.”  
 
 
 

Appendix D. Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) 
Questionnaire 
 

 
 
 

Appendix E. Well-being Questionnaire for Operating Room Staff 
Basic Information 
1. Position: 
□ Lead operator □ Assistant □ Nurse □ Anesthesiologist □ Technician 
2. Procedure duration: ______ hours ______ minutes 
3. Order of the case today: No. ______ 
4. Personal protective equipment (select all that apply): 
□ None □ Lead apron □ Lead cap □ Thyroid collar □ Lead skirt □ Lead glasses □ Dosimeter 
1. Physical Discomfort and Pain Assessment 
1.1 Do you experience any physical discomfort or pain? 
□ No → Proceed to Section 2 Radiation Exposure and Protection  □ Yes 
1.2 Please select the affected body region(s) or symptom(s): 
□ Headache □ Neck pain □ Shoulder pain  
□ Back pain □ Low back pain □ Elbow discomfort  
□ Hand discomfort □ Leg fatigue/stiffness □ Eye strain/dryness  
□ General fatigue □ Emotional distress/irritability □ Other: ______ 
1.3 Pain intensity (VAS 0–5):                                   Your score: ______ 
0 = No pain 1 = Mild 2 = Moderate 3 = Severe 4 = Very severe 5 = Unbearable 
1.4 Do you need to rest briefly before resuming work? (0–4 scale) Your score: ______ 
0 = Not at all, full of energy 1 = Slight, quick recovery 2 = Moderate, recovers after short 
rest 3 = Marked, needs clear rest 4 = Severe, must rest before continuing 
2. Radiation Exposure and Protection Assessment 
2.1 Level of concern about radiation exposure (0–10): Your score: ______ 
0 = Not concerned → 10 = Extremely concerned 
2.2 Do you think radiation protection measures affect your health? 
□ Not at all □ Slightly □ Considerably □ Severely 
2.3 Do you monitor radiation dose per procedure? 
□ Always □ Sometimes □ Never 
2.4 If fluoroscopy-free procedures without heavy protective gear are available, would you 
choose them?   □ Yes □ No