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The contact electrogram and its architectural determinants in persistent human atrial fibrillation: understanding the electroarchitecture of the arrhythmic substrate

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Title: The contact electrogram and its architectural determinants in persistent human atrial fibrillation: understanding the electroarchitecture of the arrhythmic substrate
Authors: Qureshi, Norman
Item Type: Thesis or dissertation
Abstract: The understanding of the underlying mechanisms of the persistence of atrial fibrillation remains poor. Key to this is the relationship between structure - myocardial architecture, and function - electrical activity, and how these can be measured, interpreted and correlated clinically. We sought to address the hypothesis that the local electrogram morphology is determined by local atrial myocardial activation patterns, which are in turn determined by local atrial myocardial architecture. In addressing this hypothesis, we utilised improved techniques of atrial segmentation and detection of wall enhancements to more accurately delineate underlying de novo atrial myocardial fibrosis, with late-gadolinium enhanced cardiac magnetic resonance imaging (LGE- CMRI). Here, we demonstrated a predilection of native structural remodelling on the posterior left atrial wall. The electrophysiological changes underlying late-gadolinium enhancements were interrogated with high-density electroanatomic 3D mapping using a Kernel as a unit of measure, in the varying rhythms of AF, sinus and pacing, with drop in tissue voltages and conduction velocities in regions of fibrosis, but counter-intuitively, a higher extent of electrogram fractionation in healthy myocardium. We observed the rate and wavefront-activation dependency of voltage, emphasizing the importance of voltage maps being interpreted in the context of its rhythm. We have also described a novel technique of AF voltage mapping, with the metric of mean AF voltage sampled over 8 secs correlating well with LGE-CMRI defined fibrosis, and surprisingly better than that of sinus rhythm voltage suggesting that this metric may be more representative of the underlying atrial substrate. Lastly, reverse translational cell monolayer experiments in novel co-cultured neonatal ventricular rat myocytes and fibroblasts were carried out to corroborate clinical in vivo observations under the control of the basic science laboratory. These emphasized the contributions of the structural and functional changes to electrogram morphology (voltage and fractionation). The contact electrogram is the result of a complex dynamic functional electrophysiology, and its interactions with the underlying atrial myocardium. This increased understanding of structure and function (electroarchitecture) provides mechanistic insights essential if we are to progress beyond the current empiricism of catheter ablation strategies of persistent AF.
Content Version: Open Access
Issue Date: Sep-2016
Date Awarded: Jan-2017
URI: http://hdl.handle.net/10044/1/56363
DOI: https://doi.org/10.25560/56363
Supervisor: Kanagaratnam, Prapa
Francis, Darrel
Peters, Nicholas
Sponsor/Funder: Imperial College Healthcare Charity
Wellcome Trust (London, England)
Department: National Heart & Lung Institute
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:National Heart and Lung Institute PhD theses



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