Elaine Y. Wan

The aim of the AFA-ARC (Atrial Fibrillation Ablation Academic Research Consortium) initiative is to reexamine trial design and the safety and effectiveness end points for pivotal clinical trials evaluating catheter ablation for the treatment of symptomatic atrial fibrillation to provide meaningful and interpretable data to support regulatory decision-making. Beginning in July 2024, a group of international experts began meeting regularly both virtually together and separately in working groups (group 1 effectiveness end points; group 2 safety end points; and group 3 trial design and report forms), with one in-person meeting held in April 2025, and revisions of draft proposals from January 2025 to February 2026. The Food and Drug Administration Office of Cardiovascular Devices at the Center for Devices and Radiological Health provided input throughout the revision and proposal process. A patient advocate participated in the in-person meeting and during the revision phase. Heart Rhythm Society leadership was involved throughout the process and in the revision phase. Industry representatives were sent drafts of the proposed manuscripts during the revision phase before submission. The result of this process was the creation of a combined document to reexamine trial design and the safety and effectiveness end points for pivotal clinical trials evaluating catheter ablation of atrial fibrillation. This document represents contributions from each of the 3 Working Groups. The Heart Rhythm Society endorsed this document. This AFA-ARC document proposes revised effectiveness and safety end points, study design, and report forms for studies evaluating AF ablation in patients with symptomatic paroxysmal, persistent, or longstanding persistent AF.

Pulsed field ablation has rapidly reshaped the landscape of atrial fibrillation ablation by offering a nonthermal, tissue-selective alternative to conventional thermal energy. This review highlights the scientific foundations, preclinical evidence, and engineering advances that established pulsed field ablation as a safer, faster, and more precise technology. We discuss how irreversible electroporation achieves myocardial selectivity, the pivotal studies that confirmed preservation of nearby structures, and the evolution of modern catheter systems designed for efficient and durable lesion creation. As pulsed field ablation platforms continue to mature, they are redefining procedural safety standards and expanding therapeutic possibilities in cardiac electrophysiology.

Electrical and structural remodeling of the heart can contribute to the development of cardiac arrhythmias. Ex vivo optical mapping has been used to visualize cardiac electrophysiological properties, activation and phase maps to further elucidate the mechanisms of atrial fibrillation and ventricular fibrillation initiation and persistence. Here we show an epicardial three-dimensional panoramic optical mapping tool integrated with micro-computed tomography automatically segmented with a deep learning model relying on a convolutional neural network to provide structural and electrical activation information in a single three-dimensional volume of a mouse heart. This technique allows for the acquisition and analysis of electrical activity of the entire epicardial surface with submillimeter spatial resolution and a temporal resolution of 1 ms. We establish the use of this method in transgenic mouse hearts with spontaneous atrial fibrillation and ventricular fibrillation, and mouse surgical models of myocardial infarction and left ventricular hypertrophy.

Background: Accurate identification of macro-reentrant atrial tachycardia (AT) circuits is critical for successful ablation but remains challenging with conventional mapping techniques. The aim of this study was to automatically detect macro-reentrant AT loops from high-density local activation time (LAT) maps. Methods: We developed an algorithm for automated detection of macro-reentrant AT circuits using LAT-derived directed graphs. Compared to previous graph-based approaches, the algorithm is designed to identify the fastest-conducting reentrant pathways and cluster them by rotational orientation (clockwise vs. counterclockwise) to distinguish single- from dual-loop circuits. The algorithm was applied retrospectively to 60 macro-reentrant scar-related AT cases mapped with CARTO or Ensite from two institutions. The results were compared with blinded expert electrophysiologist annotations of loop location and single- vs. dual-loop classification. Results: The 60 cases included 16 right atrial and 44 left atrial ATs from 51 patients. Expert review identified 57% single-loop and 43% dual-loop circuits. Compared with expert annotation, the algorithm correctly identified anatomical loop locations with 88% accuracy and correctly distinguished single- vs. dual-loop ATs in 93% of cases. Conclusion: Our LAT graph-based algorithm automatically identified single- and dual-loop macro-reentrant AT circuits. Localizing these pathways may provide insight into circuit mechanisms and help guide ablation. CLINICAL PERSPECTIVE: What is Known: Accurate characterization of macro-reentrant atrial tachycardias (ATs) is essential for effective catheter ablation, yet identifying these circuits from local activation time (LAT) maps remains challenging and operator dependent. What the Study Adds: We developed and validated a graph-based algorithm that automatically identifies macro-reentrant AT circuits from LAT maps with high agreement compared to expert electrophysiologist annotation. The algorithm localizes reentrant loop pathways and distinguishes single- from dual-loop circuits. Localizing these pathways may provide insight into circuit mechanisms and help guide ablation.

Background: Conventional transvenous dual-chamber pacemakers may have deleterious effects on the left ventricle, such as pacing-induced cardiomyopathy for those with a high pacing burden. Although the effect of right ventricular (RV) pacing on left ventricular function has been well studied, its impact on RV remodelling and function is not well established. Methods: This systematic review and meta-analysis were constructed according to PRISMA guidelines. We searched Embase, PubMed and SCOPUS using MeSH terms, associated keywords and Boolean operators from inception to March 2024. Relevant studies reported on at least one component of RV function following RV pacing, including: change in RV ejection fraction (RVEF), pulmonary artery systolic pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), RV volume, tissue Doppler-derived tricuspid lateral annular systolic velocity (S′), 2D fractional area change (FAC), RV index of myocardial performance (RIMP) and tricuspid regurgitation. Results: In all, 18 studies, enrolling 1,220 patients, were examined to analyse the effect of RV pacing on RV echocardiographic parameters. The meta-analysis revealed that RV pacing influenced several echocardiographic parameters. RVEF showed a pooled mean difference of 2.28% (95% CI [−1.2818, 5.8385]; p=0.21), whereas TAPSE (−0.0444 cm; 95% CI [−0.1976, 0.1089]; p=0.57) and RIMP (−0.0714; 95% CI [−0.2888, 0.1459]; p=0.52) exhibited small, non-significant reductions in pooled mean difference. In contrast, S′ pooled mean difference decreased significantly (−1.3522 cm/s; 95% CI [−2.3647, −0.3396]; p=0.0089), but there were no significant changes in FAC% (−0.1208 %; 95% CI [−3.6630, 3.4215]; p=0.95) or sPAP (3.7282 mmHg; 95% CI [−6.0651, 13.5216]; p=0.46) pooled mean difference. Heterogeneity was high across all RV function parameters examined, with I² values exceeding 89%. Length of treatment was not significantly associated with changes in RVEF (p=0.21), TAPSE (p=0.53), S′ (p=0.22), or FAC% (p=0.68), but significantly influenced RIMP (p=0.01). Site of pacing significantly affected TAPSE (p=0.0198), S′ (p=0.0124), FAC% (p=0.0014) and sPAP (p=0.0006). Apical pacing was consistently associated with the worst outcomes across parameters, including the greatest negative impact on TAPSE, S′ and sPAP, whereas left bundle branch area pacing (LBBAP) generally showed better outcomes, including the least impact on sPAP. Conclusion: RV pacing is associated with significant reductions in S′ and notable effects on other echocardiographic parameters, with heterogeneity largely driven by the site of pacing. Apical pacing had the most detrimental effects across multiple parameters, whereas LBBAP was generally associated with better outcomes. Further studies are needed to address residual heterogeneity and examine additional covariates.

Atrial fibrillation (AF) is a prevalent arrhythmia with known detriments such as heart failure, stroke, and cognitive decline even in patients without prior stroke. The mechanisms by which AF leads to cognitive dysfunction are yet unknown, and there is a lack of animal models to study this disease process. We previously developed a murine model of spontaneous and prolonged episodes of AF, a double transgenic mouse model with cardiac-specific expression of a gain-of-function mutant voltage-gated sodium channel (DTG-AF mice). Herein, we show, for the first time to our knowledge, a murine model of AF without any cerebral infarcts exhibiting cognitive dysfunction, including impaired visual learning and cognitive flexibility on touch screen testing. Mesenteric resistance arterial function of DTG-AF mice showed significant loss of myogenic tone, increased wall thickness and distensibility, and mitochondrial dysfunction. Brain pial arteries also showed increased wall thickness and mitochondrial enlargement. Furthermore, DTG-AF mice have decreased brain perfusion on laser speckle contrast imaging compared with controls. Cumulatively, these findings demonstrate that AF leads to vascular structural and functional alterations necessary for dynamic cerebral autoregulation, resulting in increased cerebral stress and cognitive dysfunction. Expression of mitochondrial catalase (mCAT) to reduce mitochondrial reactive oxygen species (ROS) was sufficient to prevent vascular dysfunction due to AF, restore perfusion, and improve cognitive flexibility.