Atrial Fibrillation (AF), Atrial Fibrillation Catheter Ablation
Conditions
Keywords
Atrial Fibrillation, Catheter Ablation, Long-standing Persistent Atrial Fibrillation, Pulsed Field Ablation, Radiofrequency Ablation
Brief summary
The goal of this clinical trial is to test if a more complete ablation procedure works better than the standard procedure for people with long-lasting atrial fibrillation (AF). AF is a heart rhythm problem that can cause a fast or uneven heartbeat. This study will include 430 people with long-lasting AF that has lasted 1 to 3 years. Participants will be put into one of two groups by chance: First group (control): They will receive pulsed-field ablation (PFA), a type of energy that can stop the faulty heart signals. They will have isolation of the pulmonary veins and the back wall of the left atrium. Second group (study): They will receive the same PFA procedure plus extra ablation lines (modified linear ablation) using radiofrequency energy. This includes ablation of the mitral isthmus (with ethanol infusion into a small vein called the vein of Marshall) and the cavotricuspid isthmus. Participants will be followed for 12 months after the procedure with clinic visits, electrocardiograms (ECGs), and heart rhythm monitors. The main outcome is whether participants stay in normal heart rhythm (sinus rhythm) without any AF episodes lasting more than 30 seconds at 12 months. Researchers will also look at procedure time, complication rates, quality of life, and other rhythm outcomes. This study will help show if the more complete ablation procedure leads to better long-term results for people with long-lasting AF.
Detailed description
Atrial fibrillation (AF), often called AFib, is the most common type of irregular heartbeat. Normally, the heart beats in a steady rhythm. In AF, the upper chambers of the heart (the atria) beat very fast and irregularly, which prevents blood from being pumped out completely. People with AF may feel heart palpitations (a racing or fluttering feeling), dizziness, shortness of breath, fatigue, and chest discomfort. Over time, AF increases the risk of blood clots, stroke, heart failure, and other serious health problems. What is long-standing persistent AF? AF is classified by how long it lasts. This study focuses on long-standing persistent AF, which is defined as continuous AF that lasts for more than 12 months. In this form of AF, the heart's upper chambers have undergone significant changes-often called "atrial remodeling." These changes make the heart tissue more prone to sustaining irregular rhythms and make the condition harder to treat compared to shorter-lasting forms of AF. Many patients with long-standing persistent AF continue to have symptoms even after trying antiarrhythmic medications (drugs designed to control heart rhythm), and finding an effective treatment remains a challenge. Why is this study needed? Catheter ablation is a procedure that uses energy to create small scars in specific areas of the heart to block abnormal electrical signals. Pulmonary vein isolation (PVI) is the standard ablation procedure for AF, where the doctor isolates the areas where most abnormal signals start. However, in patients with long-standing persistent AF, PVI alone is often not enough. Studies show that only about half of patients remain in normal heart rhythm 12 months after PVI alone. Researchers believe that additional ablation lines-created along specific pathways outside the pulmonary veins-may help block more abnormal electrical circuits and improve outcomes. The main challenge is that doctors do not yet know which combination of ablation lines works best. Newer energy technologies may also help. Pulsed field ablation (PFA) is a new, non-thermal ablation technology that uses short, high-voltage electrical pulses to kill heart cells that cause abnormal signals. Unlike traditional heat-based methods (such as radiofrequency ablation), PFA is more selective. It targets heart tissue while causing less damage to nearby structures like the esophagus (the tube connecting the throat to the stomach) and the phrenic nerves (which control breathing). This makes PFA potentially safer for treating areas near these sensitive structures. Radiofrequency (RF) ablation uses heat and remains a reliable method for creating precise, targeted lesions. This study combines both technologies: PFA for isolating the pulmonary veins and the back wall of the left atrium, and RF for creating additional linear lesions. What does this study aim to find out? The main goal of this study is to determine whether adding extra ablation lines-specifically the mitral isthmus line (supplemented by ethanol infusion into the vein of Marshall) and the cavotricuspid isthmus line-to the standard PVI plus posterior wall isolation can help more patients with long-standing persistent AF stay in normal heart rhythm at 12 months after the procedure. The study will also compare the two treatment groups in terms of safety, procedure time, AF burden, quality of life, and other health outcomes. What type of study is this? This is a prospective, multicenter, randomized, controlled trial. "Prospective" means participants are followed forward in time. "Multicenter" means the study is being conducted at multiple hospitals. "Randomized" means participants are assigned to one of two treatment groups by chance (like flipping a coin) to ensure that the groups are similar and the results are reliable. "Controlled" means the outcomes of the new treatment are compared against a standard treatment. How many people will take part? A total of 430 participants will be enrolled across multiple centers in China. Who can join? To be eligible, participants must: Be between 18 and 75 years old Have long-standing persistent AF that has lasted between 1 and 3 years Have symptoms of AF (such as palpitations, fatigue, or shortness of breath) that did not improve after trying at least one antiarrhythmic medication Have a left atrial diameter between 43 mm and 55 mm (measured by echocardiogram, a type of heart ultrasound) Have a documented AF episode within the 3 years before joining the study Be willing and able to follow the study procedures and sign an informed consent form Participants cannot join if they have certain other heart conditions (such as previous heart surgery or a left atrial thrombus), have had a previous AF ablation procedure, have a left atrial diameter larger than 55 mm, have severely reduced heart pumping function, or have other serious medical conditions that would make study participation unsafe. What happens during the study? After joining the study, participants will be randomly assigned to one of two groups. Group 1 (Control group) - Standard ablation: Participants in this group will receive PFA to isolate the pulmonary veins (the large veins that carry blood from the lungs to the heart) and to create a "box lesion" that isolates the posterior wall of the left atrium. This combination (PVI plus posterior wall isolation) is currently a common approach for treating long-standing persistent AF. Group 2 (Study group) - Modified linear ablation: Participants in this group will receive the same PFA to isolate the pulmonary veins and the posterior wall of the left atrium. In addition, they will receive RF ablation to create two extra linear lesions: Mitral isthmus (MI) line - an ablation line along the area between the mitral valve (which controls blood flow between the left atrium and left ventricle) and the left inferior pulmonary vein. This ablation is supplemented by infusing a small amount of alcohol (ethanol) into the vein of Marshall (a small vein in the heart wall) to help create a more complete and lasting block. Cavotricuspid isthmus (CTI) line - an ablation line at the bottom of the right atrium that targets abnormal electrical signals that can cause a different type of fast heartbeat called atrial flutter. Both procedures are performed under sedation or general anesthesia (medication to make the participant sleep and not feel pain). The doctor guides a thin, flexible tube called a catheter through a vein in the leg up to the heart to deliver the ablation energy. What is the follow-up schedule? Participants will be followed for 12 months after the procedure. Follow-up visits will occur at 1 month, 3 months, 6 months, 9 months, and 12 months. At these visits, participants will undergo: Physical exams Electrocardiograms (ECGs, which record the heart's electrical activity) 24-hour Holter monitoring (at 1 and 3 months) or 3-day Holter monitoring (at 6, 9, and 12 months) - these are portable heart rhythm recorders that the participant wears at home Echocardiograms (at 3, 6, and 12 months) - an ultrasound of the heart to check its structure and function Quality of life questionnaires (the AFEQT and EQ-5D-5L surveys) to assess how AF and the treatment affect daily life Neurocognitive assessments to evaluate memory and thinking skills Recording of any symptoms, medications, or health events between visits In addition, participants will be asked to use a portable heart monitor whenever they feel heart symptoms between scheduled visits. What is the main outcome being measured? The primary outcome is the percentage of participants who remain in normal sinus rhythm (regular heart rhythm) at 12 months after the procedure, excluding a 3-month blanking period right after the procedure when the heart is healing and temporary rhythm changes do not count as failure. This means that between 3 months and 12 months after the procedure, participants must not have any episode of AF, atrial flutter, or atrial tachycardia lasting more than 30 seconds, recorded by ECG or Holter monitor. What other outcomes will be measured? Secondary outcomes include: The need for repeat ablation or electrical cardioversion (a procedure that uses a small electric shock to restore normal rhythm) AF burden (the total amount of time the heart spends in AF over the follow-up period) Procedure time, ablation time, and radiation exposure during the procedure Improvement in quality of life scores Changes in cognitive function Occurrence of any complications or adverse events What are the risks? As with any medical procedure, catheter ablation carries risks. Possible risks include bleeding or infection at the catheter insertion site, bruising, damage to blood vessels, perforation of the heart wall (which may require drainage), stroke or blood clot, damage to the phrenic nerve (which could affect breathing), narrowing of the pulmonary veins, and formation of a fistula (an abnormal connection) between the left atrium and the esophagus. PFA is a newer technology that may have a lower risk of certain complications-such as damage to the esophagus or phrenic nerve-compared to traditional heat-based ablation methods. However, as with any new medical device, there may be unknown risks. The ethanol infusion into the vein of Marshall carries its own small risks, including pain, spasm of the heart artery, or inflammation around the heart. The study doctor will explain all known risks before asking for consent, and participants will be closely monitored for any complications. What are the possible benefits? Participants in the study group may benefit from the additional ablation lines, which could lower their chance of AF returning compared to the standard approach. Participants in both groups may experience fewer AF symptoms, better heart function, and an improved quality of life. However, there is no guarantee of benefit, and some participants may not improve. The results of this study may also help future patients with long-standing persistent AF by providing evidence to guide treatment decisions. How will participant privacy be protected? All participant information will be kept confidential. Participants will be identified by a unique study number rather than by name in any study records or reports. The study results will be published only as summary data, without any information that could identify individual participants. Who is conducting this study? This study is led by the Department of Cardiology at Beijing Anzhen Hospital, Capital Medical University, in collaboration with multiple centers across China. Study period The study will enroll participants from approximately June 2026 to December 2027, with follow-up completed by December 2028. The total study period is approximately 3.5 years.
Interventions
DEVICEPulsed Field Ablation Catheter
Use of a pentaspline pulsed field ablation (PFA) catheter to perform circumferential pulmonary vein isolation (PVI) and left atrial posterior wall box isolation. The endpoint is confirmed bidirectional block of all targeted veins and the posterior wall.
DRUGEthanol
Infusion of absolute ethanol into the vein of Marshall (VOM) under balloon occlusion to facilitate mitral isthmus linear ablation.
Use of a contact-force sensing radiofrequency (RF) ablation catheter to create modified linear lesions: mitral isthmus line (combined with ethanol infusion) and cavotricuspid isthmus line. The goal is bidirectional block across all linear lesions.
Sponsors
Yunlong Wang
Beijing Huahsia Foundation
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
This is a single-blind study. Participants are blinded to their assigned treatment group (control vs. study). Procedure operators are not blinded due to the nature of the interventions. All other study personnel involved in outcome assessment (e.g., ECG core laboratory, Holter analysis) and statistical analysis are blinded to group assignment.
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups. The control group receives pulsed-field ablation (PFA) for pulmonary vein isolation and posterior wall isolation. The study group receives the same PFA procedure plus additional modified linear ablation using radiofrequency energy (mitral isthmus line supplemented by ethanol infusion into the vein of Marshall, and cavotricuspid isthmus line). No cross-over between groups is planned.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Symptomatic patients with long-standing persistent atrial fibrillation. * Duration of atrial fibrillation between 1 and 3 years. * Age 18 to 75 years. * Left atrial diameter between 43 mm and 55 mm. * Documentation of atrial fibrillation within 3 years prior to enrollment. * Willing and able to comply with the study protocol and provide written informed consent.
Exclusion criteria
* Paroxysmal atrial fibrillation, or evidence of sinus rhythm on electrocardiogram within the past year. * Persistent atrial fibrillation lasting less than 1 year or more than 3 years. * Left atrial thrombus. * Prior catheter ablation for atrial fibrillation. * Coexisting severe organic heart disease (e.g., severe valvular heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, etc.). * Left atrial diameter (LAD) \>55 mm. * Left ventricular ejection fraction (LVEF) \<40%. * Known allergy or contraindication to low-molecular-weight heparin, warfarin, or direct oral anticoagulants. * Undergoing a "one-stop" procedure combining atrial fibrillation ablation with left atrial appendage closure. * Allergy to alcohol or contrast media. * Pulmonary artery systolic pressure \>50 mmHg. * Unstable angina pectoris. * Percutaneous coronary intervention (PCI) within the past 3 months. * Cardiac surgery within the past 6 months. * Planned heart transplantation. * History of thromboembolic disease within the past 6 months (including venous thromboembolism: pulmonary embolism, deep vein thrombosis; or arterial thromboembolic disease: acute coronary syndrome, lower extremity arterial embolism, stroke). * Left atrial myxoma. * Severe respiratory disease. * Active infectious disease. * Poorly controlled or active systemic immune disease (equivalent to glucocorticoid use \>2 tablets/day). * Unresolved malignant hematologic disease, or currently receiving chemotherapy, radiotherapy, or immunotherapy. * Unresolved malignant solid tumor, or currently receiving chemotherapy, radiotherapy, or immunotherapy. * Untreated hypothyroidism or hyperthyroidism. * Severe hepatic insufficiency (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>3 times the upper limit of normal). * End-stage renal failure requiring dialysis. * Other serious arrhythmias, such as hemodynamically unstable ventricular tachycardia. * Pregnancy or breast-feeding. * Psychiatric disorder. * Body mass index (BMI) \<18.5 or \>35.0 kg/m². * Life expectancy \<2 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom from Atrial Arrhythmia Recurrence at 12 Months | Between 3 months and 12 months following the ablation procedure, excluding the initial 3-month blanking period | The primary outcome is the proportion of participants remaining in normal sinus rhythm at 12 months after the ablation procedure, after excluding a 3-month blanking period immediately following the procedure. Treatment success is defined as freedom from any documented episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds, as recorded by electrocardiogram (ECG) or Holter monitoring between 3 months and 12 months post-ablation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Atrial Fibrillation Burden at 12 Months | From month 3 to month 12 after the ablation procedure | AF burden is defined as the percentage of time spent in atrial fibrillation (AF), atrial flutter, or atrial tachycardia during the 12-month follow-up period, excluding the 3-month blanking period. Burden is assessed using 24-hour Holter monitoring at 6 and 9 months and 7-day Holter monitoring at 12 months post-ablation. The percentage of AF days (defined as days on which Holter recording shows any AF/AFL/AT episode) among total monitored days will also be reported as a secondary measure. |
| Incidence of Serious Procedure-Related Complications | From the start of the ablation procedure to 30 days post-procedure | Proportion of participants experiencing at least one serious adverse event related to the ablation procedure or device. Serious complications include cardiac tamponade requiring intervention, atrio-esophageal fistula, periprocedural stroke or transient ischemic attack, pulmonary vein stenosis, hemolysis requiring renal replacement therapy, coronary events (including spasm requiring unplanned angiography), and death. |
| Cardiovascular Hospitalization During Follow-up | From the date of ablation to 12 months post-ablation | Any hospitalization for cardiovascular causes (including heart failure, arrhythmia recurrence, stroke, or other cardiac events) during the 12-month follow-up period after ablation. |
| Total Procedure Time | On the day of the ablation procedure | Total procedure time measured in minutes from first femoral venous access to final sheath removal. |
| Acute Success Rates of Linear Ablation Lesions | During the ablation procedure (intraoperative) | Procedural success for linear ablation lesions is defined as confirmed bidirectional block of the target lesion immediately after ablation, assessed by electroanatomic mapping and differential pacing maneuvers. The following specific lesion sets are evaluated: Posterior wall isolation rate: Proportion of participants in whom complete bidirectional block of the left atrial posterior wall box lesion is achieved. This is assessed in both study groups. Mitral isthmus line block rate: Proportion of participants in the study group (modified linear ablation arm) in whom bidirectional block of the mitral isthmus line is confirmed after combined ethanol infusion into the vein of Marshall and radiofrequency ablation. Cavotricuspid isthmus line block rate: Proportion of participants in the study group in whom bidirectional block of the cavotricuspid isthmus line is confirmed (only performed if typical atrial flutter is documented, otherwise not applicable). |
| Change in AFEQT Overall Score at 12 Months | Baseline and at 3 and 12 months after the ablation procedure | The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire is a 20-item, disease-specific, patient-reported instrument. It assesses the impact of atrial fibrillation on health-related quality of life across four subscales: symptoms (4 items), daily activities (8 items), treatment concerns (6 items), and treatment satisfaction (2 items). Each item is scored on a 7-point Likert scale. The overall summary score ranges from 0 to 100, with higher scores indicating better quality of life. A change of 5 points or more is considered clinically meaningful. The outcome is the change from baseline in the AFEQT overall score at each follow-up time point. |
| Change in Montreal Cognitive Assessment (MoCA) Score at 12 Months | Baseline and at 3 and 12 months after the ablation procedure | The Montreal Cognitive Assessment (MoCA) is a clinician-administered screening tool designed to detect mild cognitive impairment (MCI). It assesses multiple cognitive domains including visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation. Total scores range from 0 to 30, with higher scores indicating better cognitive function. A score of ≥26 is generally considered normal. The MoCA has greater sensitivity for detecting mild cognitive impairment compared to the MMSE. The outcome is the change from baseline in the total MoCA score at each follow-up time point. |
Countries
China
Contacts
CONTACTYunlong Wang, PhD
CONTACTYijie Liu, PhD
Outcome results
None listed