PFLotus With the DePolar Mapping System in Patients With Persistent Atrial Fibrillation

Official title

Assessment of a Novel Shape-Adaptive Catheter With for Both Single-Shot and Large-Focal Pulsed Field Ablation the DePolar Mapping System in Persistent Atrial Fibrillation

Overview

This clinical trial aims to evaluate the safety and efficacy of pulmonary vein isolation (PVI), focal, and linear ablation in patients with persistent atrial fibrillation (PersAF) using a novel shape-adaptive pulsed field ablation (PFA) catheter (PFLotus, EnChannel Medical) integrated with a novel mapping system (DePolar, EnChannel Medical). The primary study objectives are to determine: * The incidence of serious procedure- or device-related adverse events within 7 days post-procedure (primary safety endpoint). * The clinical effectiveness of the integrated PFA and mapping system. * The ability of the novel PFA system to produce durable ablation lesions. PersAF patients will be treated under general anesthesia using the PFLotus PFA catheter (bipolar, biphasic waveform; 850 V, 60 μs per pulse). Ablation targets, including PVI and other lesions (left atrial posterior wall, mitral isthmus, cavotricuspid isthmus, and superior vena cava), will be accessed under fluoroscopic and DePolar mapping system guidance. Participants will: 1. Receive PVI, focal, and linear ablation using the PFLotus PFA catheter and DePolar mapping system under general anesthesia; 2. Be monitored for serious procedure- or device-related adverse events during the first 7 days post-procedure; 3. Undergo repeat electrophysiological mapping at 3 months to assess lesion durability; 4. Attend scheduled follow-up visits at 7 days, 30 days, and 3, 6, and 12 months post-ablation. Atrial arrhythmia recurrence will be assessed via 12-lead electrocardiography at each visit and by 24-hour or 7-day Holter monitoring at the 6- and 12-month visits.

Detailed description

Background Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia worldwide, affecting an estimated 1.5-2.0% of the general population. As the population ages, the prevalence of AF continues to rise, imposing a substantial and growing burden on healthcare systems. AF significantly impairs quality of life, elevates stroke risk fivefold, triples the incidence of heart failure, and increases overall mortality.

Initial AF management typically involves pharmacotherapy for rate control or rhythm control. Compared to antiarrhythmic drugs (AADs), catheter ablation offers superior efficacy in reducing AF recurrence, lowering cardiovascular hospitalization rates, and preventing arrhythmia relapse. The cornerstone of catheter ablation is pulmonary vein isolation (PVI), which electrically isolates the pulmonary veins from the left atrium. Current guidelines recommend catheter ablation, primarily PVI, for patients with symptomatic, drug-refractory paroxysmal AF, establishing it as a standard therapy for symptomatic paroxysmal or persistent AF.

Pulsed field ablation (PFA) induces cardiomyocyte death via irreversible electroporation using high-voltage, ultra-rapid electric fields. As a non-thermal energy modality, PFA demonstrates selective myocardial tissue affinity. This characteristic may enable durable lesion formation while sparing adjacent critical structures such as the esophagus, blood vessels, pulmonary veins, and phrenic nerve. Notably, PFA has not been associated with thermal energy complications like atrio-esophageal fistula, phrenic nerve palsy, or pulmonary vein stenosis, suggesting the potential for enhanced efficacy with an improved safety profile.

Recent evidence indicates that integrating three-dimensional (3D) mapping and navigation systems into PFA procedures can reduce radiation exposure while improving procedural accuracy and clinical outcomes.

Therefore, this study aims to evaluate the safety and efficacy of PVI, focal, and linear ablation in patients with persistent AF (PersAF) using a novel shape-adaptive PFA catheter (PFLotus, EnChannel Medical) integrated with a new mapping system (DePolar, EnChannel Medical).

Methods Study Population Eligible patients were aged 18-75 years with documented symptomatic persistent AF (duration 7-365 days) who were refractory or intolerant to at least one Class I or III antiarrhythmic drug.

Procedural Workflow All procedures were performed under general anesthesia. Activated clotting time was maintained at ≥300 seconds. An electroanatomic map of the left atrium and pulmonary veins was created using the PFLotus catheter and the DePolar system.

PVI and additional ablation strategies-including ablation of the left atrial posterior wall (LAPW), mitral isthmus (MI), cavotricuspid isthmus (CTI), and superior vena cava (SVC)-were performed in all patients. For MI ablation, if persistent epicardial connections were identified, adjunctive ablation within the coronary sinus was performed. After a 20-minute waiting period, isolation and block were reassessed.

Follow-up Post-ablation antiarrhythmic drug use was determined by the operator and typically discontinued after three months. Oral anticoagulation was maintained per guidelines. Structured follow-up was conducted at 7 days and 3 months post-ablation, with lesion durability assessed via invasive remapping at 3 months. Additional visits were scheduled at 6 and 12 months. Atrial tachyarrhythmia recurrence was assessed using 12-lead ECGs at each visit and 24-hour or 7-day Holter monitoring at 3, 6, and 12 months.

Endpoints The primary safety endpoint was the incidence of primary adverse events (PAEs) within 7 days post-ablation. Later-occurring events-including device- or procedure-related death, atrio-esophageal fistula, and PV stenosis-were also classified as PAEs. Persistent diaphragmatic paralysis or phrenic nerve palsy at 3 months was considered a PAE.

The primary efficacy endpoint was acute procedural success, defined as the proportion of patients achieving: 1) complete electrical isolation of all pulmonary veins, and 2) confirmed bidirectional block at all targeted linear ablation sites (LAPW, MI, CTI, and SVC) in patients undergoing such ablation.

Secondary efficacy endpoints included:

1. Acute PV isolation success rate. 2. Acute success rate of bidirectional block for each linear ablation site. 3. Durable success rate of bidirectional block for each linear ablation site at 3-month remapping. 4. One-year freedom from atrial tachyarrhythmia recurrence.

Interventions

• Device Ablation with the PFLotus catheter and Depolar system
  PVI and additional ablation strategies-including ablation of the left atrial posterior wall (LAPW), mitral isthmus (MI), cavotricuspid isthmus (CTI), and superior vena cava (SVC)-were performed in all patients with PerAF using the PFLotus PFA catheter and Depolar mapping system.

Primary outcome measures

• Incidence of Primary Adverse Events (PAEs) Within 3 Months Post-Ablation [Primary Safety Endpoint] [Time frame: Within 3 months post the index ablation]
• Rate of Acute Procedural Success: Complete Pulmonary Vein Isolation and Bidirectional Block at Targeted Linear Ablation Sites [Primary Efficacy Endpoint] [Time frame: Immediate after the ablation procedure]

Secondary outcome measures (4)

• Rate of Acute Pulmonary Vein (PV) Isolation Success [Secondary Efficacy Endpoint] [Time frame: Immediate after the index ablation procedure]
• Acute Bidirectional Block Success Rate for Each Targeted Linear Ablation Site [Secondary Efficacy Endpoint] [Time frame: Immediate after the index ablation procedure]
• Durable Bidirectional Block Success Rate for Each Targeted Linear Ablation Site at 3-Month Remapping [Secondary Efficacy Endpoint] [Time frame: 3 months post the index ablation procedure]
• 1-Year Freedom from Atrial Tachyarrhythmia Recurrence [Secondary Efficacy Endpoint] [Time frame: 1 year post the index ablation procedure]

Eligibility criteria

Inclusion criteria

1\. Aged 18-75 years (inclusive). 2. Diagnosis of symptomatic persistent atrial fibrillation (AF), defined as documented AF episodes exceeding 7 days or a documented history of persistent AF. Additionally, at least one of the following criteria must be met within 365 days prior to enrollment:

• A 24-hour ambulatory ECG (Holter) recording demonstrating AF throughout the entire monitoring period.
• Two separate standard 12-lead ECGs, taken at least 7 days apart, both confirming AF.

3\. Documented failure or intolerance to at least one Class I or Class III antiarrhythmic drug (AAD).

4\. Willingness to participate in the trial, ability to comply with protocol-specified follow-up assessments, and provision of written informed consent.

Exclusion criteria

• Paroxysmal atrial fibrillation (AF)；
• AF caused by electrolyte disorders, thyroid diseases, or reversible/non-cardiac etiologies；
• Patients undergoing retreatment after ablation for rapid atrial tachyarrhythmias；
• Patients with sustained ventricular tachycardia or ventricular fibrillation；
• Left atrial anteroposterior diameter > 55 mm；
• Pulmonary vein (PV) stenosis (>70%) or prior PV stent implantation；
• History of left atrial ablation or cardiac surgery (including left atrial appendage closure)；
• Implantation of permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardioverter-defibrillator (with or without biventricular pacing function)；
• Contraindications to anticoagulation, or history of coagulation or bleeding abnormalities；
• Severe pulmonary disease: severe pulmonary arterial hypertension or any pulmonary disease with severe dyspnea involving blood gas abnormalities；
• Any of the following cardiac surgeries, implants, or conditions:

• Prosthetic heart valve
• NYHA Class III or IV congestive heart failure, or left ventricular ejection fraction (LVEF) < 40%
• Atrial septal defect or ventricular septal defect closure
• Atrial myxoma, left atrial appendage device implantation or occlusion
• History of any of the following within 3 months prior to the procedure:

• Myocardial infarction
• Unstable angina
• Percutaneous coronary intervention
• Cardiac surgery (including coronary artery bypass grafting)
• Hospitalization for heart failure
• Pericarditis
• History of any of the following within 3 months prior to the procedure:

• Cerebral infarction or transient ischemic attack (TIA)
• Documented thromboembolic events (e.g., confirmed by transesophageal echocardiography \[TEE\])
• History of malignant tumor or expected life expectancy < 12 months；
• Mental disorders or history of mental illness with inability to cooperate independently；
• Lactating, pregnant, or women planning or potentially becoming pregnant；
• Acute or severe systemic infection, or significant abnormalities in liver/renal function；
• Participation in other interventional clinical trials, or ineligibility for enrollment as judged by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07321002 · PFLotus with DePolar

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗