Innovative approaches for ventricular arrhythmia ablation: comparative treatments, advanced imaging, machine learning and other novel technologies

Abstract

Over the past three decades, advancements in mapping technologies have improved our understanding and treatment of ventricular arrhythmia (VA). Despite this, long-term success rates for catheter ablation (CA) in structural heart disease (SHD) have plateaued, highlighting the need for mechanistic and translational studies to refine our understanding of ventricular arrhythmogenesis and improve CA strategies. This thesis addresses the challenge of treating VA, identifying knowledge gaps and focusing on abolishing arrhythmogenic substrate. We begin with the first published systematic review comparing antiarrhythmic drugs (AADs) and CA for premature ventricular contractions (PVCs), highlighting the need for patient-centred randomised data using current ablation technologies. We then use an ovine model with co-registered whole heart histopathology, cardiac MRI (CMR), and high-density electroanatomic mapping to validate image integration of CMR scar and channels. Notably, CMR channels at sites of conduction slowing and electrogram fractionation showed higher intra-channel adiposity but similar fibrosis, suggesting lipomatous metaplasia, not fibrosis, drives postinfarction arrhythmogenicity. We also perform an inter-vendor comparison of commonly used CMR image integration software. Next, we apply novel signal processing and machine learning algorithms trained on intracardiac electrograms to accurately identify scar and its depth from endocardial-only mapping. These findings led to an open-source tool generating scar depth maps for electroanatomic mapping. We then describe a pilot case series using novel pulsed field ablation technology for treating intracavitary PVCs. Finally, we have designed a pragmatic randomised controlled trial comparing stereotactic body radiotherapy (SBRT) against standard care for VA, with recruitment underway. Overall, this work offers incremental but important improvements in VA ablation, aiming toward control and cure of these deadly arrhythmias.