Mechanism-guided treatment of atrial fibrillation: investigating the electrophysiological substrate of human atrial fibrillation
File(s)
Author(s)
Coyle, Clare
Type
Thesis
Abstract
Atrial Fibrillation (AF) is the most common arrhythmia and causes significant morbidity. Ectopic foci in pulmonary veins can trigger AF. Pulmonary vein isolation (PVI) ablation aims to manage these. Despite reducing AF burden a cure remains elusive.
The autonomic nervous system is proposed as an upstream driver of ectopy and thus AF. Endocardial high frequency stimulation (HFS) at atrial sites of dense autonomic innervation, the ganglionated plexuses (GP), triggers vagal responses (atrio-ventricular dissociating-GP [AVD-GP]) or ectopy and AF (ectopy-triggering GP [ET-GP]). Ablation of AVD-GP has inconsistent outcomes. ET-GP can be ablated in patients with paroxysmal AF with similar outcomes to PVI (GANGLIA-AF study). Here, we advance the interrogation of atrial AF-triggering sites as targets for ablation.
GP ablation (GPA) could have additive benefit to PVI. Patients undergoing repeat ablation for paroxysmal AF were randomised to redo-PVI or redo-PVI with GPA. There was no difference in outcome but rates of freedom from AF were higher with ET-GP only ablation.
GPA has been hampered by technical challenges. We developed a novel high frequency stimulator, the Tau20v1, which reproducibly identifies GP, enabling high-density GP mapping.
We tested ET-GP ablation as stand-alone therapy for persistent and long-standing persistent AF, demonstrating that left atrial GP ablation can prevent AF recurrence. However, GP mapping at repeat procedures showed GP recurrence and, if sinus rhythm not maintained, missed ET-GP. An alternative strategy to identify AF triggers is required for those unable to maintain sinus rhythm.
A novel algorithm, RETRO-map, enabled activation mapping during AF, identifying repetitive focal activation and changes in activation after PVI.
In conclusion, ET-GP may have a role as triggers in paroxysmal and persistent AF. We have developed new tools, the Tau20 and RETRO-map, to investigate AF triggers and enable targeted ablative therapy. This could lead to patient-tailored approaches to AF ablation.
The autonomic nervous system is proposed as an upstream driver of ectopy and thus AF. Endocardial high frequency stimulation (HFS) at atrial sites of dense autonomic innervation, the ganglionated plexuses (GP), triggers vagal responses (atrio-ventricular dissociating-GP [AVD-GP]) or ectopy and AF (ectopy-triggering GP [ET-GP]). Ablation of AVD-GP has inconsistent outcomes. ET-GP can be ablated in patients with paroxysmal AF with similar outcomes to PVI (GANGLIA-AF study). Here, we advance the interrogation of atrial AF-triggering sites as targets for ablation.
GP ablation (GPA) could have additive benefit to PVI. Patients undergoing repeat ablation for paroxysmal AF were randomised to redo-PVI or redo-PVI with GPA. There was no difference in outcome but rates of freedom from AF were higher with ET-GP only ablation.
GPA has been hampered by technical challenges. We developed a novel high frequency stimulator, the Tau20v1, which reproducibly identifies GP, enabling high-density GP mapping.
We tested ET-GP ablation as stand-alone therapy for persistent and long-standing persistent AF, demonstrating that left atrial GP ablation can prevent AF recurrence. However, GP mapping at repeat procedures showed GP recurrence and, if sinus rhythm not maintained, missed ET-GP. An alternative strategy to identify AF triggers is required for those unable to maintain sinus rhythm.
A novel algorithm, RETRO-map, enabled activation mapping during AF, identifying repetitive focal activation and changes in activation after PVI.
In conclusion, ET-GP may have a role as triggers in paroxysmal and persistent AF. We have developed new tools, the Tau20 and RETRO-map, to investigate AF triggers and enable targeted ablative therapy. This could lead to patient-tailored approaches to AF ablation.
Version
Open Access
Date Issued
2024-09-03
Date Awarded
2025-08-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Kanagaratnam, Prapa
Linton, Nicholas
Sponsor
British Heart Foundation
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)