Atrial Remodeling After PFA Substrate Modification for Persistent AF (PeAF)

Overview

Atrial fibrillation (AF) is associated with both electrical and structural remodeling of the left atrium. While successful catheter ablation has been shown to reverse some aspects of atrial remodeling, the impact of pulsed-field ablation (PFA) - a non-thermal ablation technology that selectively targets cardiomyocytes while sparing surrounding structures - on atrial remodeling in patients with persistent AF undergoing extensive substrate modification remains unclear. This is a prospective, single-center, single-arm observational study conducted at Taipei Veterans General Hospital. The study will enroll 30 patients with persistent atrial fibrillation who undergo pulmonary vein isolation (PVI) and extensive substrate modification using the FARAWAVE / FARADRIVE Catheter and FARASTAR System. The primary objective is to evaluate left atrial structural remodeling following PFA, including changes in LA size, atrial strain, extent of atrial fibrosis, and atrial hemodynamic function. The secondary objective is to assess AF-free survival between 3 and 12 months after the procedure, and its relationship to atrial remodeling. All participants will be followed for 12 months, with an interim analysis conducted once all subjects complete their 6-month follow-up.

Background and Rationale Atrial fibrillation (AF) is associated with progressive electrical and structural remodeling of the left atrium. Electrical remodeling typically reverses within a week after restoration of sinus rhythm, whereas structural remodeling takes longer - generally 2 to 4 months - and successful ablation has been shown to improve left atrial transport function. Pre-procedural assessment with echocardiographic left atrial strain and delayed-enhancement MRI may help predict the extent of reverse remodeling after ablation. Pulsed-field ablation (PFA) is a non-thermal ablation technology that uses pulsed electric fields to create focal lesions selectively targeting cardiomyocytes, while largely sparing surrounding structures such as the esophagus, phrenic nerve, and blood vessels. Compared with radiofrequency ablation (RFA), PFA can create larger and deeper lesions with fewer applications, with a potentially reduced risk of collateral injury. Beyond pulmonary vein isolation (PVI), PFA has also been applied to other atrial substrates, including the posterior wall and mitral line. A recent study suggested that mean pulmonary arterial pressure did not worsen in patients with pre-existing pulmonary hypertension undergoing repeat PFA for recurrent AF. However, the impact of PFA on atrial remodeling in patients with persistent AF undergoing extensive substrate modification remains unknown. This study aims to characterize changes in atrial function and structural remodeling 3 to 12 months after PFA for PVI and extensive substrate modification, and to explore its relationship with procedural outcomes. Study Design This is a prospective, single-center, single-arm observational clinical investigation conducted at Taipei Veterans General Hospital. Thirty patients with persistent AF will undergo the index ablation procedure using the FARAWAVE Catheter, FARADRIVE Catheter, and FARASTAR System (Boston Scientific). Enrollment will cease once approximately 30 subjects have been accrued. An interim endpoint analysis will be performed once all subjects have completed their 6-month follow-up. All participants will be followed for up to 12 months. Procedure Pre-procedural care will follow the standard institutional protocol for AF ablation cases, with AF classification (paroxysmal vs. non-paroxysmal) defined according to the 2024 HRS consensus on catheter ablation of AF. Pre-procedural evaluation includes transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), cardiac CT and MRI, and 14-day Holter monitoring. The ablation procedure is performed under deep sedation or general anesthesia, with PFA targeting pulmonary vein isolation and posterior wall isolation. Additional substrate modification may be performed using PFA at the physician's discretion. Conventional invasive hemodynamic assessment of left atrial function - including mean pulmonary artery pressure (mPAP), pulmonary arterial wedge pressure, cardiac output, vascular resistance, and right atrial pressure - will be performed before and after PFA during the procedure. Post-procedural assessments include 12-lead ECG and in-hospital Holter monitoring within 3 days following PFA. At 3 to 12 months after the procedure, participants will undergo repeat echocardiography, cardiac CT and MRI, ECG, and 14-day Holter monitoring. Invasive hemodynamic assessment will be repeated approximately 3 months after the procedure. Endpoints The primary endpoint is left atrial structural remodeling, including changes in LA size, atrial strain, extent of atrial fibrosis, and other atrial hemodynamic functions. The secondary endpoint is AF-free survival within 3 to 12 months following PFA. The main scientific question is to elucidate atrial remodeling following non-thermal ablation with PFA and its relationship to ablation outcomes. Safety Monitoring All adverse events (AEs) and serious adverse events (SAEs) will be captured and classified by the investigator according to relatedness (procedure-related, device-related, cardiovascular-related, arrhythmia-related, heart failure-related), seriousness, timing (pre-procedure, during ablation, post-ablation), and diagnosis. Pre-specified serious adverse events of interest include cardiac tamponade or perforation, death, esophageal perforating complications, gastric motility / pyloric spasm disorders, heart block, myocardial infarction, hospitalization due to cardiovascular or pulmonary PFA system- or procedure-related events, pericarditis, peripheral or organ thromboembolism, pulmonary vein stenosis, severe hemolysis with subsequent renal failure or significant anemia, stroke, transient ischemic attack, unresolved phrenic nerve palsy or paresis, and vascular access complications.