Novel Mapping and Therapeutic Techniques for Treatment of Ventricular Arrhythmias

Ventricular arrhythmias (VAs) are a leading cause of cardiovascular morbidity and sudden cardiac death (SCD). It is estimated that SCD and VA account for 15-20% of all deaths worldwide. Despite the decline in cardiovascular deaths over recent decades, the incidence of sudden cardiac death as a proportion of overall cardiovascular mortality has increased. Medical therapy to prevent sudden arrhythmic death has been shown to be ineffective. Institution of implantable cardiac defibrillators has been shown to reduce mortality from malignant VAs, but these devices do nothing to prevent VAs from occurring. Subsequently catheter ablation for VAs, particularly ventricular tachycardia (VT), is now part of standard of care. Advancement in electroanatomical mapping and ablation technology has led to further insights into VT circuits and the functional nature of the substrate that sustains them. The aim of this thesis was to investigate the diagnostic, mechanistic, and therapeutic techniques used for the treatment of VAs occurring in the presence of structural heart disease. There was a particular focus on the functional assessment of the VT substrate, and how this provides insight into where critical sites of VT re-entry are harboured. Initially, novel therapies for treatment of VAs were reviewed, and a systemic review and meta-analysis was conducted on the role of renal denervation. Subsequently, assessment of the VT circuit was investigated using novel modalities such as an automated conduction velocity mapping algorithm and direct graph mapping (DGM). Analysis of the substrate was then performed using a novel retrospective window of interest (WOI) approach. Finally, a direct comparison of different techniques for annotating local activation time (LAT) was performed. Chapter 1 outlines current understanding of VT and ventricular fibrillation (VF) mechanisms and treatment. Contemporary methods for performing a substrate-based VT ablation are explored. The role of imaging in VA