Aggressive Risk Factor Reduction Study for Atrial Fibrillation (ARREST-AF)

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with evidence from epidemiological data confirming the emergence of AF as a global epidemic. Although population ageing is regarded as an important contributor, several risk factors such as hypertension, diabetes mellitus, obesity, and obstructive sleep apnoea have been epidemiologically linked as promoters of AF. Cardiac risk factors are associated with structural and electrical remodeling of the atria that form the substrate leading to the development and progression of AF. Evidence from animal studies suggests that management of these risk factors such as obesity can reverse some of these changes. This was associated with reduced vulnerability of AF. However, impact of risk factor management on atrial fibrillation in human has not been evaluated. Furthermore, mechanism and degree of reversibility of substrate in humans, where multiple factors can play a role, with weight and other risk factor management has not been described. This thesis evaluates the reversal of atrial substrate with weight and other risk factor management and its impact on AF freedom and AF ablation outcome. Chapter 2 assesses the long-term impact of weight-loss and weight-fluctuation on rhythm control in obese individuals with AF. In over-weight and obese individuals with symptomatic AF, progressive weight-loss had a dose-dependent effect on long-term freedom from AF. Additionally, weight-fluctuation of >5% had an adverse effect on overall freedom from AF with a two-fold greater likelihood of recurrent arrhythmia. Chapter 3 evaluated the impact of cardiorespiratory fitness on long-term freedom from atrial fibrillation (AF). It also looked at the impact of cardiorespiratory fitness gain on AF outcome. This study demonstrates that in overweight and obese individuals with symptomatic AF, preserved baseline cardiorespiratory fitness predicts long-term freedom from AF. Cardiorespiratory fitness gain with a structured exercise program had an additive effect to weight-loss in improving the long-term outcome of AF. Chapter 4 evaluated the impact of aggressive risk factor management on the outcomes of the catheter ablation. In patients with symptomatic AF undergoing ablation, a structured physician-directed risk factor and weight management program resulted in significant improvement in the long-term outcomes. Chapter 5 evaluated the impact of risk factor management on the electrophysiological and electroanatomical properties of the atria, cardiac structure and endothelial and platelets function. Aggressive risk factor management was associated with marked structural improvement with a reduction in atrial size, regression of ventricular mass and normalization of bipolar voltages. There was a resultant significant improvement in the electrophysiological properties with marked improvement in conduction properties and tissue refractoriness. Mechanistically, there was a reduction in pericardial fat volumes and serum fibrosis markers. Furthermore, there was improvement in endothelial function, platelet function and inflammatory markers. These changes were associated with significant reduction in the AF vulnerability and clinical burden of AF. Chapter 6 evaluated the cost effectiveness of a goal dedicated physician led clinic on the outcomes of the catheter ablation. This program is not only clinically effective but also cost-effective in terms of improvement in QALYs and reduction in AF burden.