The Effect of Low-Level Tragus Stimulation on Inflammation and Early Recurrence After Pulsed Field Ablation: A Randomized Controlled Study

Atrial fibrillation is a common cardiac arrhythmia. Pulsed field ablation is increasingly used for the treatment of atrial fibrillation because it can achieve pulmonary vein isolation through non-thermal electroporation and has shown a favorable safety profile. However, some patients may still experience early atrial arrhythmia recurrence after ablation. Post-procedural inflammation and autonomic nervous system imbalance may both contribute to early atrial arrhythmia recurrence after ablation.

Low-level tragus stimulation is a non-invasive neuromodulation technique applied to the external ear region. Previous studies suggest that stimulation of the auricular branch of the vagus nerve may influence autonomic regulation and inflammatory responses. However, it remains unclear whether low-level tragus stimulation can reduce inflammatory responses after pulsed field ablation and decrease early atrial arrhythmia recurrence.

This study is designed as a prospective, randomized,parallel-controlled clinical trial. After screening according to the eligibility criteria, eligible participants will be randomly assigned after pulsed field ablation to either the low-level tragus stimulation group or the sham stimulation group. Participants in the low-level tragus stimulation group will receive active low-level tragus stimulation according to the study protocol. Participants in the sham stimulation group will receive sham stimulation that does not provide effective therapeutic stimulation.

The study will collect clinical data, laboratory test results, and heart rhythm monitoring data. These data will be used to evaluate changes in inflammatory responses after ablation and to monitor atrial arrhythmia events. Participants will continue to be followed after discharge to assess early atrial arrhythmia recurrence.

The main objective of this study is to evaluate whether low-level tragus stimulation after pulsed field ablation can reduce post-procedural inflammatory responses and decrease early atrial arrhythmia events in patients with atrial fibrillation.This exploratory study may provide preliminary data to support future studies on low-level tragus stimulation as a potential strategy for blanking-period management after pulsed field ablation.

Inclusion criteria

• Age 18 to 80 years, inclusive.
• Diagnosed with paroxysmal or persistent atrial fibrillation by electrocardiogram or ambulatory electrocardiogram, and scheduled to undergo first catheter ablation for atrial fibrillation.
• Able to understand and sign the written informed consent form, and willing to participate in this study.
• Willing and able to comply with the follow-up requirements specified in the study protocol.

Exclusion criteria

• History of two or more previous catheter ablation procedures for atrial fibrillation.
• Scheduled to undergo concomitant cardiac surgery or other interventional procedures during the index procedure.
• History of cervical vagus nerve injury, abnormal ear anatomy, skin lesions, or other conditions that may prevent correct placement or tolerance of the auricular vagus nerve stimulation electrode.
• Left ventricular ejection fraction less than 40%.
• New York Heart Association functional class III or IV.
• Severe hepatic or renal dysfunction, defined as alanine aminotransferase or aspartate aminotransferase greater than two times the upper limit of normal, or estimated glomerular filtration rate less than 30 mL/min/1.73 m².
• Known inflammatory disease, connective tissue disease, active infection, or long-term use of glucocorticoids, non-steroidal anti-inflammatory drugs, or immunosuppressive agents for more than 4 weeks.
• Acute myocardial infarction or unstable angina within 3 months before enrollment.
• Percutaneous coronary intervention or coronary artery bypass grafting within 3 months before enrollment.
• Stroke or transient ischemic attack within 3 months before enrollment.
• Severe uncontrolled hypertension, defined as resting systolic blood pressure of 180 mmHg or higher, or resting diastolic blood pressure of 110 mmHg or higher.
• Sick sinus syndrome, second-degree type II atrioventricular block, or third-degree atrioventricular block without implantation of a permanent pacemaker.
• Pregnancy, lactation, or planned pregnancy during the study period.
• Participation in another drug or medical device clinical trial within 3 months before enrollment.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for this study, such as expected survival less than 1 year or poor compliance.