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Title: The action potential duration and repolarization of the human ventricle and its relation to the body surface ECG
Author: Srinivasan, Neil Thomas
ISNI:       0000 0004 7964 8642
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Repolarization dispersion has been associated with increased risk of cardiac arrhythmia in animal studies, but whether it is present in humans and how its manifests on the surface ECG is unknown. This thesis aimed to bridge the gap between our basic cellular and intracardiac understanding of cardiac electrical activity with the surface ECG focusing specifically on cardiac repolarization and the surface ECG. Restitution studies in humans with structurally normal and abnormal hearts were performed, looking at transmural and regional gradients of repolarization. The data were then analysed to assess the association of intracardiac repolarization with the surface T-wave. Finally a novel non-invasive ECG (ECGI) was used to study the electrical substrate in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). In normal human heart restitution studies epicardial APD was shorter than endocardial APD, with smaller differences in the apicobasal orientation. It was found that, local repolarization times in the right and left ventricle occur along the upslope of the body surface T-wave in leads V1-V3 and V5,V6 and Lead-I respectively; and the difference between the end of the upslope in V1 and V6 provides a good representation of right to left dispersion of repolarization. In patients with structurally abnormal hearts myocardial scar, regardless of pathology, resulted in prolonged APD compared to normal healthy tissue diminishing transmural gradients of APD and resulting in localised transmural dispersion of repolarization. Finally ECGI characterised the electrophysiological substrate in ARVC, demonstrating prolonged APD in these patients compared to control patients. ECGI was able to demonstrate the presence of electrophysiological changes before changes were visible on cardiac MRI. In conclusion, this work shows that APD gradients are present in the intact human heart, and can be demonstrated both using contact electrophysiological mapping and on methods that incorporate the body surface ECG.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available