Characterisation of the structural and electrical impact of an atrial septal defect in humans

Student thesis: Doctoral ThesisDoctor of Philosophy


This thesis addresses the important issue of atrial arrhythmia (AA) in patients with atrial septal defects (ASD). It describes the structural and electrical changes that occur in the atria of patients with unclosed ASDs and the relationship between these changes and the presence of AAs.
ASDs constitute one of the most common congenital heart lesions, with AAs representing a major cause of morbidity in this population. Little is known about the unique bi-atrial arrhythmia substrate in these patients and as result rhythm management strategies are extrapolated from guidelines for the non-congenital heart disease (CHD) population. It is not clear whether ASD closure alone is sufficient to treat AAs in this cohort or whether adjunct catheter ablation should be considered at the time of closure in selected patients. In order to better guide arrhythmia management and, in particular, catheter ablation strategies in the future, an improved understanding of the structural and electrophysiological factors contributing to arrhythmogenesis is required.
While timely ASD closure may reduce the prevalence of atrial arrhythmia, no recent evaluation of the effects of percutaneous ASD closure, the gold standard method of closure today, exists in the literature. As a first step in this thesis, meta-analysis was performed in order to address the question of whether percutaneous, device ASD closure alone can affect the prevalence of atrial arrhythmia in an ASD cohort, representing the most up-to-date and extensive assessment on this subject.
A comprehensive evaluation of the arrhythmia substrate in the secundum ASD population was subsequently undertaken using complementary invasive and non-invasive techniques.
No data exists to date regarding the assessment of atrial fibrosis in ASD patients, using cardiac magnetic resonance (CMR) imaging, a well-described technique in arrhythmia substrate characterisation in non-congenital heart disease (CHD) patients with atrial fibrillation. In this thesis, structural remodelling in ASD patients with and without AAs was assessed by quantifying CMR derived fibrosis using established imaging techniques, the first evaluation of its kind to be reported.
Only two prior studies exist detailing invasive parameters of electrical remodelling in the ASD cohort, both of which involved small numbers and predated recent advances in electroanatomic mapping technology. In this study the bi-atrial electrical substrate in ASD patients with and without AAs was characterised invasively by measuring LA and RA voltage, conduction velocity and refractoriness using a contemporary electroanatomic mapping system, representing the most comprehensive evaluation of bi-atrial electrical remodelling in this population to date.
Furthermore, while atrial ectopy is well described in the non-CHD population as a trigger for atrial fibrillation, little is known about the drivers or triggers for AAs in the ASD cohort. This thesis presents a detailed assessment of arrhythmia triggers performed through invasive and non-invasive assessment of atrial ectopy using novel techniques not previously described.
A control group consisting of non-CHD patients with paroxysmal AF served as a comparison group and underwent the same protocol as the ASD patients for both non-invasive and invasive components of this thesis.
The aims of this thesis can be summarized as follows 
1. To evaluate the effects of percutaneous ASD closure on the prevalence of atrial arrhythmia in this cohort 
2. To investigate the extent of bi-atrial structural and electrical remodelling occurring in patients with an uncorrected ASD and the relationship between these parameters and the presence of atrial arrhythmia. 
3. To evaluate the origin of atrial ectopy as potential sites for atrial arrhythmia triggers 
The original hypotheses explored in this thesis are as follows:
1. Percutaneous closure may reduce the overall prevalence of atrial arrhythmias in the ASD cohort. 
2. Structural and electrical remodelling may predominate in the right atrium in patients with uncorrected ASDs and the right atrium is important to atrial arrhythmogenesis in this population 
3. Arrhythmia triggers and sites of atrial ectopy will be present in the right atrium of ASD patients
The findings of this thesis contribute a significant body of knowledge to the subject of atrial arrhythmia in the ASD population and may have important implications for rhythm management strategies in the future. 
Date of Award1 Apr 2021
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorMark O'Neill (Supervisor) & Steven Williams (Supervisor)

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