Pulsed-Field Ablation for Recurrent Atypical Atrial Flutter

Recurrent atypical atrial flutter (AFL) after prior atrial fibrillation or flutter ablation remains challenging to treat, and conventional radiofrequency ablation may be limited by incomplete lesion formation and risk of collateral damage. Pulsed-field ablation (PFA) uses non-thermal electric fields to create myocardial lesions with relative sparing of surrounding tissues and may improve the safety and efficacy of ablation for atypical AFL. This prospective, non-randomized, single-arm study will enroll approximately 30 patients with clinically documented recurrent atypical AFL who are referred for elective catheter ablation using a point-by-point pulsed-field ablation system. During the index procedure, detailed electroanatomic mapping will be performed to identify the critical isthmus or circuit, followed by linear or focal PFA and confirmation of bidirectional conduction block. The primary safety endpoint is the incidence of procedure- and device-related primary adverse events. The primary effectiveness endpoint is acute procedural success, defined as termination of atypical AFL and establishment of bidirectional block across the targeted lesion set at the end of the procedure. Secondary endpoints include recurrence of any atrial arrhythmia during 12-month follow-up, durability of the linear lesions assessed by repeat electroanatomic mapping at 3 months, changes in atrial scar on cardiac MRI, peri-procedural changes in blood biomarkers, and the rate of serious adverse events related to the procedure or study device.

Atypical atrial flutter (AFL) is a challenging atrial tachyarrhythmia that frequently occurs after prior catheter ablation for atrial fibrillation (AF) or AFL. Conventional radiofrequency ablation (RFA) can be limited by variable lesion size and depth, difficulty in achieving durable transmural linear block, and the risk of collateral injury to adjacent structures such as the esophagus, phrenic nerve, and coronary arteries. These limitations are particularly important in recurrent atypical AFL, where complex macro-reentrant or localized reentrant circuits often form along prior ablation scars or in regions of epicardial conduction in the posterior left atrium and pulmonary veins, making durable ablation difficult to achieve. Pulsed-field ablation (PFA), based on non-thermal irreversible electroporation, has emerged as a promising technique that can create deep, contiguous lesions with preferential myocardial injury while sparing non-cardiac tissues. Early clinical experience with point-by-point PFA systems has demonstrated high acute and chronic success rates for pulmonary vein isolation and linear ablation with low complication rates in patients with recurrent AF or AFL after prior ablation. These data suggest that focal PFA may overcome some of the safety and efficacy limitations of conventional thermal energy sources. This single-center, prospective, non-randomized, single-arm clinical investigation will enroll approximately 30 adult patients with clinically documented recurrent atypical AFL after prior AF/AFL ablation within 5 years who are scheduled for elective repeat ablation. The investigational system is the Biosense Webster Dual Energy Pulsed Field/Radiofrequency Ablation System, consisting of the TRUPULSE™ Generator, the Dual Energy THERMOCOOL SMARTTOUCH™ SF (STSF) catheter, and the CARTO™ 3 System with VISITAG SURPOINT™ Module. Standard-of-care adjunctive devices (e.g., OCTARAY™ mapping catheter, DECANAV™ diagnostic catheter, VIZIGO™ sheath, and intracardiac echocardiography \[ICE\] catheter) will be used as appropriate. Eligible subjects are ≥18 years of age with recurrent atypical AFL documented by ECG or electrophysiologic study after prior pulmonary vein isolation and/or AFL ablation, including gap-reentrant, perimetral, roof-dependent, bi-atrial, or scar-related circuits, and who are willing and able to provide informed consent and complete follow-up. Key exclusion criteria include AFL due to reversible causes, recent major cardiac events or surgery, significant structural heart disease (e.g., severe valvular disease, hypertrophic cardiomyopathy, markedly enlarged left atrium), severe ventricular dysfunction, significant pulmonary or renal disease, active malignancy or infection, untreated severe sleep apnea, contraindication to anticoagulation, pregnancy, vulnerable populations, and limited life expectancy. After signing informed consent, subjects will undergo baseline evaluations including 12-lead ECG, 14-day Holter monitoring, transthoracic echocardiography, transesophageal echocardiography, and cardiac MRI at least one day before the ablation procedure. Oral anticoagulation will be managed according to guideline-based practice, with at least 4 weeks of pre-procedural anticoagulation and continued post-procedural anticoagulation per current clinical standards. The index procedure will be performed under general anesthesia or deep sedation. A deflectable decapolar catheter will be positioned in the coronary sinus. Double transseptal puncture will be performed under fluoroscopic and ICE guidance, followed by systemic heparinization to maintain an activated clotting time of 300-350 seconds. Bi-atrial electroanatomic maps will be created with the CARTO® 3 system and high-density mapping catheters. ICE will be used systematically for transseptal guidance, catheter navigation, and surveillance of pericardial effusion, posterior wall-esophagus distance, pulmonary vein ostial dimensions, and valvular function before, during, and after ablation. A transthoracic echocardiogram will be performed immediately after the procedure or before discharge to detect complications. Mapping of atypical AFL or atrial tachycardia will follow established protocols from the investigators' prior work. If the patient is in sinus rhythm, arrhythmia will be induced using atrial pacing and isoproterenol infusion. High-density activation and entrainment mapping will be performed to characterize the reentrant circuit(s) or localized reentry, with post-pacing interval (PPI) analyses at multiple sites; a PPI within 20 ms of the tachycardia cycle length will be considered within the circuit. Circuits will be classified as macro-reentrant or localized reentry based on activation patterns. Once the critical isthmus or focal source has been identified, the Dual Energy STSF catheter connected to the TRUPULSE™ Generator will be used to deliver point-by-point PFA along the targeted line of block or boundary of the critical zone, aiming to interrupt the reentrant loop or focal driver. Lesions will be applied at approximately 3-5 mm spacing with contact force maintained at 10-20 g. Pulse delivery and tag indices (PF Index/RF Tag Index) will be titrated according to anatomical location, with higher index targets at anterior sites and lower targets at posterior wall regions near the esophagus. A maximum number of applications per location will be predefined. The acute endpoint is termination and non-inducibility of atypical AFL and demonstration of bidirectional conduction block across any linear lesion, confirmed by activation mapping and differential pacing. If AFL does not terminate or bidirectional block cannot be achieved after up to two passes of PFA, conventional RFA using the same catheter and generator will be permitted as a bail-out strategy and considered acute treatment failure for the primary effectiveness endpoint. After ablation, inducibility testing will be performed with burst atrial pacing, with or without isoproterenol, to confirm non-inducibility of atypical AFL. Peri-procedural complications and device-related events will be carefully monitored and recorded. Primary adverse events include major complications such as cardiac tamponade, stroke or transient ischemic attack, major vascular complications, atrioesophageal fistula, pulmonary vein stenosis, and procedure- or device-related death, among others, occurring within 7 days of the index ablation (or up to 90 days for delayed events as appropriate). Safety oversight will include pre-specified reporting to the sponsor, institutional review board, and regulatory authorities, as well as periodic review by an independent Data and Safety Monitoring Board (DSMB) with planned interim safety analyses. All subjects will be followed clinically for 12 months after the index procedure. A 12-lead ECG will be obtained before hospital discharge. Outpatient follow-up visits will occur approximately 2 weeks after PFA and then every 1-3 months. At each visit, symptoms, medications, and adverse events will be assessed and ECGs recorded. Fourteen-day Holter monitoring will be scheduled at 3, 6, 9, and 12 months, and additional 24-hour Holter or event monitoring will be performed for symptomatic episodes. Recurrent AF/AFL is defined as any atrial tachyarrhythmia (AF, atrial tachycardia, or AFL) lasting \>30 seconds after a 3-month blanking period. Cardiac MRI with late gadolinium enhancement will be performed at baseline and at 3 and 12 months post-ablation to quantify atrial scar burden and evaluate changes in scar distribution and lesion durability over time. Blood biomarkers (including liver enzymes, cardiac enzymes, inflammatory markers, and haptoglobin) will be collected before and after ablation and at 3, 6, 9, and 12 months to characterize myocardial injury and inflammatory responses to dual-energy ablation. All patients will be recommended to undergo a repeat electrophysiology study and repeat electroanatomic mapping at approximately 3 months (±4 weeks) to directly assess the durability of PFA linear lesions and confirm persistent bidirectional block across prior ablation lines. In cases of reconnection of previous PFA lines, touch-up RFA will be performed per investigator discretion. However, reconnection without documented atrial arrhythmia lasting \>30 seconds will not count as a clinical recurrence for the secondary effectiveness endpoint. The primary safety endpoint is the incidence of predefined primary adverse events within 7 days of the index procedure. The primary effectiveness endpoint is acute procedural success, defined as termination and non-inducibility of atypical AFL with confirmed bidirectional block across ablation lines at the end of the procedure. Secondary endpoints include freedom from recurrent atrial arrhythmias at 12 months, durability of linear lesions on repeat mapping, changes in atrial scar on MRI, serial biomarker profiles, and serious adverse events related to the procedure and/or investigational device. This feasibility study is designed to generate prospective clinical data on the safety, acute procedural success, arrhythmia outcomes, lesion durability, and myocardial/inflammatory response associated with point-by-point PFA using the BWI Dual Energy system in patients with recurrent atypical AFL after prior ablation. The results are expected to inform future larger studies and may help refine ablation strategies and energy delivery parameters for complex post-ablation atrial tachyarrhythmias.