Medicine (RMH) - Theses
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ItemA multi-faceted approach to atrial fibrillation: from lifestyle factors to invasive therapies( 2019)Atrial fibrillation (AF) is a leading epidemic of cardiovascular disease in developed countries, owing to an ageing population and the Western lifestyle. In addition to effects on quality of life and economic burden on the health system, AF is associated with heart failure, stroke and a higher risk of mortality. The focus of AF management over the last decade has shifted from anticoagulation and rate control to a more a more holistic and multi-faceted approach. This encompasses attention to potentially modifiable lifestyle factors and adoption of novel invasive strategies such as catheter ablation to maintain rhythm control. The aim of this thesis is to explore these emerging strategies in AF management, with a focus on rhythm control. Initially, we assess the impact of lifestyle related factors on AF and cardiovascular disease. The emphasis initially is on the effects of habitual alcohol consumption on the atria and ventricles and the impact of abstinence in the AF population. We explore novel strategies for cardioversion of persistent AF, focussing on improving success rates in obese patients. Finally, we explore the evolution of catheter ablation as an increasingly utilized rhythm control strategy. Chapter 1 details our evolving understanding of AF pathogenesis, and the impact of common lifestyle factors on arrhythmogenesis, with a focus on alcohol, caffeine, diet and obesity. We then explore the evidence base for rhythm control strategies, including role of anti-arrhythmics, cardioversion and catheter ablation. Chapter 2 and 3 explore the impact of regular alcohol consumption on the atrium to determine whether there is an association with electrical and structural remodelling. Chapter 2 is a prospective observational study of 75 patients undergoing novel high-density electroanatomical mapping of their left atria at the time of AF ablation. We compare non-drinkers, mild drinkers and moderate drinkers to determine whether there are differences in voltage and conduction properties between the three groups. Chapter 3 is a prospective observational study of 160 AF patients comparing atrial size, mechanical and reservoir function based on degree of alcohol intake utilizing high-definition cardiac magnetic resonance imaging (CMR). We conclude that moderate-to-heavy levels of consumption are associated with adverse atrial remodelling, characterised by reduction in voltage, slowing of atrial conduction, atrial dilatation and impaired mechanical function suggestive of progressive fibrosis. Chapter 4 is a randomized controlled trial of 140 moderate habitual drinkers with a history of AF. We examine the impact of 6 months of abstinence on risk of AF recurrence, AF burden, symptom scores, blood pressure, weight and atrial structure / function. Key findings include reduction in AF recurrence rates, with small but significant reductions in systolic blood pressure and weight. This is the first randomized trial to demonstrate the benefits of abstinence from alcohol in the AF population. Chapter 5 examines the paradox between adverse effects of moderate alcohol consumption on the atrium and AF with widely reported benefits of light-to-moderate habitual alcohol consumption with respect to cardiovascular disease, heart failure and mortality. We undertook a cross-sectional study of 165 stable outpatients comprising of lifelong non-drinkers and regular drinkers. Participants underwent cardiac MRI T1 mapping, a novel imaging sequence that examines markers of ventricular fibrosis. Interestingly, light-to-moderate drinkers displayed lower markers of fibrosis. The clinical implications of this finding require further investigation. Chapter 6 focusses on novel and improved treatment strategies for persistent AF in obese patients. We undertook a randomized controlled trial of 125 obese patients undergoing cardioversion for AF (as well as an observational sub-study of morbidly obese patients). Key findings included higher success rates with the use of hand-held paddles, manual pressure augmentation and higher energies (up to 360 Joules biphasic). Chapter 7 also focuses on improving outcomes for cardioversion in persistent AF, looking at the strategy of early presentation for cardioversion in the emergency department. We report a retrospective cohort study of 150 patients and conclude that compared to (delayed) elective cardioversion, earlier restoration of sinus rhythm prevented adverse atrial remodelling, delaying onset of next AF recurrence and improving quality of life. Chapter 8 examines our evolving understanding of ablation strategies for persistent AF. Recent studies highlight that adjunctive substrate modification beyond pulmonary vein isolation (PVI) may not offer additional benefit and may in fact be pro-arrhythmic. We perform a meta-analysis of 14 studies reporting outcomes from PVI alone in this patient population. We conclude that with current technology, acceptable arrhythmia-free survival can be achieved without additional substrate modification. Chapters 9 and 10 report observational data from our institution with the aim of critically assessing key performance measures for catheter ablation of AF over time. Chapter 9 demonstrates a significant reduction in radiation exposure over time for both operator and patient, and examines the factors responsible. Chapter 10 focuses on procedural safety over time through the prism of increasing patient complexity, greater operator experience and technological advances over time. We conclude that at a high-volume centre, catheter ablation is an acceptable strategy that can be performed safely in a large majority of patients.