Medicine (RMH) - Theses
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ItemNovel Mechanisms, Determinants and Therapies in Atrial Fibrillation( 2023-01)Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder and is associated with increased morbidity and mortality. Since the first description of AF initiation by triggers from pulmonary veins sleeves, pulmonary vein isolation has become the standard ablation strategy in patients with AF. However, freedom from the arrhythmia particularly in persistent AF remains suboptimal and it is now clear that in these patients AF is maintained by an atrial substrate beyond the pulmonary veins. This thesis aims to evaluate novel mechanisms that influence the atrial substrate in AF (chapters 2,3, and 4), the role of genetic predisposition on the atrial substrate and arrhythmia outcomes post ablation (chapter 5), and the impact of catheter ablation on cognitive function, markers of psychological distress, and arrhythmia outcomes (chapters 6, 7, and 8). Chapter 1 outlines our current understanding of the atrial substrate in atrial fibrillation and its association with traditional risk factors for AF. We delineate the role of genetics in AF, focusing on the AF-polygenic risk score and its role in AF management. Lastly, we review the impact of catheter ablation on cognitive function, markers of psychological distress, and catheter ablation timing on arrhythmia outcomes. Chapter 2 describes the electroanatomic characteristics and ablation outcomes in a case series of symptomatic patients with a clinical syndrome of atrial tachycardia/atrial fibrillation and extensive right atrial free wall substrate. An extensive low voltage zone in the trabeculated RA free wall constituted an unusual substrate for AF. These patients also demonstrated unstable atrial tachycardias originating from the same zone. Radiofrequency ablation to render the low voltage zone electrically inert was an effective strategy to manage AF and atrial tachycardia and improve symptoms. Chapter 3 characterises the wavefront activation patterns of extent of left and right atrial septal electrical dissociation in a cohort of 8 patients with longstanding persistent AF. Two advisor HD grid catheters were positioned on either side of the interatrial septum and unipolar recordings of AF and sinus rhythm were analysed offline. We observed complete wavefront dissociation between the left and right interatrial septum with no evidence of transseptal conduction, indicating that the two sides function as electrically discrete structures. No stable septal drivers were observed. Chapter 4 characterises the wavefront activation pattern at the pulmonary vein (PV) sleeve in 13 patients with longstanding AF using high density phase mapping. Pulmonary vein sleeve unipolar recordings were collected during AF using the 64-electrode Baskett Catheter. A robust inverse mapping technique was used to reconstruct the recorded unipolar atrial EGMs on the PV surface and the resulting phase maps were used to identify incoming and outgoing wavefronts (WF) at the PV junction (reentry), and focal and rotor activity originating within the PV sleeves. Electrical activity generated by PV sleeves during PeAF was due mainly to macroscopic reentry initiated by incoming waves, frequently with a ratio>1. That is, the PVs act less as AF drivers than as “echo chambers” which sustain and amplify fibrillatory activity. Chapter 5 examines the association between AF-polygenic risk score (AF-PRS), the left atrial substrate and ablation outcomes. Amongst 95 patients who their AF-PRS calculated and detailed electroanatomic mapping of the left atrium, we observed that patients with high AF-PRS had more advanced left atrial electrical remodelling and lower arrhythmia free survival post ablation when compared to low AF-PRS. Chapter 6 focuses on the impact of catheter ablation on cognitive function in a cohort of 100 patients randomised to catheter ablation versus medical therapy. All patients underwent 6 neurocognitive tests at baseline, 3, 6, and 12 months. A reliable change index was calculated to detect changes compared to baseline. We observed that in patients randomised to catheter ablation there was higher prevalence of new onset cognitive dysfunction at 3 months post catheter ablation when compared to medical therapy. However, this was transient and fully reversible at 12 months with no observed cases of cognitive dysfunction. In addition, 14% of patients in the ablation arm demonstrated improvements in their cognitive function at 12 months compared to medical therapy (0%). Chapter 7 examines the impact of catheter ablation on markers of psychological distress in a cohort of 100 patients randomised to catheter ablation versus medical therapy. All patients underwent comprehensive psychological testing using the Hospital Anxiety and Depression Score (HADS) and Beck Depression Inventory Score (BDI-II). In addition, Quality of life measures were assessed using the AF symptoms severity score (AFSSS) and the Short Form-36 questionnaire (SF-36). Patients randomised to the ablation arm reported improvement in their makers of psychological stress (HADS and BDI-II) in addition to improvement in qualify life measures. This improvement was associated with sinus rhythm and cessation of antiarrhythmic medications during follow up. Chapter 8 evaluates the impact of AF catheter ablation timing on arrhythmic recurrence outcomes. A total of 89 patients were randomised to either undergo ablation within 1 month of recruitment (early ablation arm) or 12 months after recruitment (delayed ablation arm). All patients were followed up for 12 months and their arrhythmia recurrence, AF burden and antiarrhythmic drug use was recorded. Both groups had comparable atrial arrhythmia free survival, median AF burden and antiarrhythmic drug use at 12 months.