Atrial fibrillation nomenclature, definitions, and mechanisms: Position paper from the international Working Group of the Signal Summit

Abstract

The international Working Group of the Signal Summit is a consortium of experts in the field of cardiac electrophysiology dedicated to advancing knowledge on understanding and clinical application of signal recording and processing techniques. In 2023, the working group met in Reykjavik, Iceland, and laid the foundation for this manuscript. Atrial fibrillation (AF) is the most common arrhythmia in adults, with a rapidly increasing prevalence worldwide. Despite substantial research efforts, advancements in elucidating the underlying mechanisms of AF have been relatively modest. Since the discovery of pulmonary veins as a frequent trigger region for AF initiation more than 2½ decades ago, advancements in patient care have primarily focused on technologic innovations to improve the safety and efficacy of pulmonary vein isolation (PVI). Several factors may explain the limited scientific progress made. First, whereas AF initiation usually begins with an ectopic beat, the mechanisms of initiation, maintenance, and electrical propagation have not been fully elucidated in humans, largely owing to suboptimal spatiotemporal mapping. Second, underlying structural changes have not been clarified and may involve different types of reentry. Third, inconsistent definitions and terminology regarding fibrillatory characteristics contribute to the challenges of comparing results between studies. Fourth, a growing appreciation for phenotypical differences probably explains the wide range of clinical outcomes to catheter ablation in patients with seemingly similar AF types. Last, restoring sinus rhythm in advanced phenotypic forms of AF is often not feasible or may require extensive ablation with minimal or no positive impact on quality of life. The aims of this international position paper are to provide practical definitions as a foundation for discussing potential mechanisms and mapping results and to propose pathways toward meaningful advancements in AF research, ultimately leading to improved therapies for AF.

Keywords: Ablation; Atrial fibrillation; Definitions; Mapping; Mechanisms; Treatment.

Figure 1.

Schema demonstrating the complex interrelationship between triggers, propagation patterns, drivers and substrate remodeling that contribute to initiation and perpetuation of AF. EAD=early afterdepolarizations, DAD=delayed afterdepolarizations.

Figure 2

Left panel: simultaneously obtained opposite endo-epicardial local activation maps and potential voltage maps constructed during AF; corresponding electrical asynchrony map shows asynchrony up to 88ms. Examples of opposite endo-epicardial electrograms are demonstrated outside the map and clearly show the asynchronous activation. Right panel: simultaneously obtained opposite sub-endocardial and sub-epicardial activation maps obtained by near-infrared optical mapping (NIOM, 350x350um resolution) during AF show focal breakthrough activation with star on sub-epicardial map and complete re-entry common path of micro-anatomic re-entry with solid green arrow on sub-endocardial map. Corresponding transmural activation delay map shows up to 100 ms sub-endocardial delayed activation along the common path of the re-entry, 3D high resolution contrast-enhanced MRI (95 um³ voxel size) defines intramural common reentrant track formed by several fibrotically insulated sub-endocardial-intramural myocardial bundles; targeted ablation of the common path of micro-anatomic re-entry terminated persistent AF confirming driver mechanism.

Figure 3.

In-vivo: Computational guidance of AF ablation (OPTIMA approach). Top: Patient-derived atrial geometry and fibrosis distribution (left). Activation map after rapid pacing and virtual PVI ablation, with yellow arrows identifying re-entry. Bottom: Sites of ablation delivery (with catheter tip locations marked by red dots) in the left atrium, as rendered by the CARTO intracardiac mapping system at the end of the clinical ablation procedure. Dashed ellipses indicate the locations ablated based on the locations of persistent reentrant drivers, as identified by OPTIMA. Ex-vivo: Ex-vivo human donor heart with persistent AF was mapped using panoramic near-infrared optical mapping (NIOM) with four CMOS cameras (100x100 pixels, 0.3–1mm²/pixel resolution) and contrast-enhanced MRI (9.2 T with 100μm³ isotropic resolution). Top, left: 3D distribution of intramural fibrosis in the NIOM-defined driver region (red) and the whole atria (blue); Bottom, left: 3D atrial wall thickness variations; Bottom, right: 3D transmural myofiber orientation from epicardium (Sub-Epi, blue) to endocardium (Sub-Endo, red). Top, right: The heart-specific 3D human atrial computer model reproduces reentrant AF driver (white arrow) defined by ex-vivo NIOM in right atria (yellow arrow). The ablation strategy that created a linear transmural ablation lesion (green dotes) through the driver reentrant track to the nearby physical border terminated AF, as seen in the atrial action potential recoding below. ^, Abbreviations: AF, atrial fibrillation; AWT, atrial wall thickness; CT, crista terminalis; IVC/SVC, inferior/superior vena cava; LSPV/LIPV/RSPV/RIPV, left superior/left inferior/right superior/right inferior pulmonary vein; MRI, magnetic resonance imaging; RAA, right atrial appendage.