FIH of PFBalloon for PVI

Overview

The goal of this clinical trial is to assess the safety and effectiveness of a conformal pulsed field ablation (PFA) balloon catheter for pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). It will also explore the durable effectiveness of this novel catheter through post-ablation remapping. The main questions it aims to answer are: Does the conformal PFA balloon catheter achieve absence of periprocedural primary adverse events (primary safety endpoint)? Does the conformal PFA balloon catheter achieve acute PVI (primary effectiveness endpoint) and durable PVI at three months post-ablation (secondary effectiveness endpoint)? This is a first-in-human, single-center trial that employs a novel PFA balloon catheter with a biphasic, bipolar 750 V waveform. The balloon is inflated with a 10:1 saline/contrast mixture, with deployment volume adjusted to form a sphere shape for wide-antral PV ablation or a pear shape for targeted ostial-junction ablation to ensure optimal tissue contact. Participants will: Undergo PVI using the novel conformal PFA balloon catheter; Be monitored for periprocedural primary adverse events to assess safety; Undergo remapping at three months post-ablation to assess durable PVI; Undergo follow-up visits scheduled for seven-days, 30-days, three-months, six-months, and 12-months post-procedure. Recurrence assessment includes: 1) routine 12-lead ECG examination during each visit and 2) 24-hour or seven-day Holter monitoring at six and 12 months.

Background Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia globally, with an estimated incidence of 1.5-2.0% in the general population. This condition markedly diminishes quality of life, elevates stroke risk fivefold, triples the incidence of congestive heart failure, and is associated with increased overall mortality. These adverse consequences primarily result from rapid, irregular ventricular rates and ineffective atrial contraction, which compromise cardiac output. The ensuing atrial dyssynchrony promotes blood stasis, elevating the risk of thrombus formation and subsequent ischemic stroke. Diagnosis is confirmed by electrocardiographic (ECG) documentation of chaotic atrial electrical activity. First-line management typically involves pharmacotherapy targeting either ventricular rate control or rhythm control-the restoration and maintenance of sinus rhythm. However, antiarrhythmic drugs are limited by proarrhythmic potential, diminishing long-term efficacy, and possible increased mortality, especially in patients with ventricular dysfunction. Catheter ablation offers superior outcomes, including reduced AF recurrence, fewer cardiovascular hospitalizations, and decreased arrhythmia relapse. Current guidelines recommend ablation for symptomatic, drug-refractory paroxysmal AF, with pulmonary vein isolation (PVI) established as the foundational procedural strategy. Conventional thermal ablation using radiofrequency or cryoenergy is an established, effective treatment for achieving PVI. However, the non-selective nature of thermal energy carries a risk of collateral damage to adjacent structures, potentially leading to rare but serious complications. Each modality presents specific trade-offs: radiofrequency ablation is technically demanding and time-intensive, while cryoballoon ablation offers ease of use but less precision for ablating non-pulmonary vein targets. Pulsed field ablation (PFA) utilizes high-voltage, ultra-rapid electrical pulses to induce irreversible electroporation and non-thermal cell death. This energy source demonstrates high cardiomyocyte selectivity, thereby sparing adjacent critical structures such as the esophagus, phrenic nerve, and pulmonary veins. Notably, PFA has not been associated with typical thermal complications like atrioesophageal fistula, phrenic nerve palsy, or pulmonary vein stenosis. By minimizing collateral injury, PFA holds promise for enhancing the safety profile of PVI without compromising efficacy. A novel, single-shot, 24-electrode, conformable balloon-based PFA catheter has been developed. Its design incorporates mid-voltage (750V) biphasic pulses delivered in a bipolar fashion between balloon electrodes, integrated tissue-contact verification, and conformability to accommodate variable anatomy. This report details the first-in-human experience evaluating this novel conformable PFA balloon catheter for PVI in patients with paroxysmal AF, assessing procedural performance, safety, acute effectiveness, and PVI durability via invasive remapping. Methods Study Design This prospective, single-arm, single-center, first-in-human (FIH) trial evaluated the safety and effectiveness of a novel conformable PFA balloon catheter (PFBalloon™, EnChannel Medical, China) for treating paroxysmal AF. The protocol was approved by the local Ethics Committee and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent. Enrolled subjects underwent first-time PVI and are being followed for 12 months post-ablation. Study Population Eligible patients were aged 18-75 years with documented symptomatic paroxysmal AF (episode duration \<7 days), who were refractory or intolerant to at least one Class I or III antiarrhythmic drug. Key exclusion criteria included reversible or non-cardiac causes of AF, prior AF ablation or surgery, anticipated need for extra-PVI ablation, persistent AF, left atrial diameter \>50 mm, left ventricular ejection fraction \<40%, presence of an implantable cardiac device, or intracardiac thrombus. Procedural Workflow After enrollment and baseline bloodwork, left atrial computed tomography angiography was performed for thrombus exclusion and anatomical assessment. Pre-procedure, thrombus was further ruled out by transesophageal echocardiography. Phrenic nerve function was evaluated via diaphragmatic motion during inspiration and direct pacing before and after ablation. Procedures were performed under general anesthesia. Following femoral venous access, intravenous heparin was administered to maintain an activated clotting time ≥300 seconds. Pre-ablation electroanatomic mapping was performed using a PENTARAY® catheter with the CARTO™ 3 system (Biosense Webster, USA). The PFA balloon catheter was positioned in the left atrium over a guidewire. PVI was performed sequentially (left superior/inferior, then right superior/inferior veins). Each vein received eight PFA applications: four at the antrum with the balloon in a spherical configuration and four at the ostium with a pear-shaped configuration, achieved by adjusting contrast inflation volume. The catheter was slightly rotated after every two applications. Positioning was optimized using fluoroscopically-guided contrast injection. Conduction block was confirmed after a 20-minute waiting period, and post-ablation voltage mapping verified acute isolation. Additional lesions were applied if necessary. Brain Magnetic Resonance Imaging Brain MRI with diffusion-weighted imaging was performed within 72 hours pre-procedure and 48 hours post-procedure to screen for acute silent cerebral ischemic events. Scans were reviewed by independent neuroradiologists. Follow-up Post-ablation antiarrhythmic drug use was permitted per operator discretion and discontinued after three months. Oral anticoagulation was continued per guidelines. All patients underwent repeat invasive electrophysiological mapping at 90 days. Clinical follow-up occurred at 7 days, 30 days, 3, 6, and 12 months. Recurrence was assessed via 12-lead ECG at each visit and 24-hour or 7-day Holter monitoring at 6 and 12 months. Study Endpoints The primary safety endpoint was the incidence of primary adverse events (PAEs) within 7 days post-ablation. Later-occurring events (device/procedure-related death, atrio-esophageal fistula, PV stenosis) were also considered PAEs. Persistent diaphragmatic paralysis/phrenic nerve palsy at 3 months were classified as PAEs. The primary effectiveness endpoint was acute procedural success, defined as confirmation of entrance/exit block in all targeted pulmonary veins. Secondary effectiveness endpoints included: 1) patient-based durable PVI rate at 3-month remapping, 2) vein-based durable isolation rate at 3-month remapping, and 3) clinical efficacy at one year.