The remodelled atrium: causes, and implications for curative ablation

© 2012 Dr. Caroline MediAtrial fibrillation has been described as an evolving epidemic in the setting of an aging population. Ongoing research into the atrial substrate responsible for maintaining atrial fibrillation is fundamental to therapeutic advances. There have been considerable advances in ablation techniques aimed at treating and potentially curing atrial fibrillation. To date success has been achieved predominantly in patients with paroxysmal atrial fibrillation with structurally normal hearts where presumably the triggers are more important than the substrate. The developments of technology and ablation techniques are currently evolving more rapidly than an understanding of their impact on the remodeled atria. It remains unclear whether “sinus rhythm begets sinus rhythm” a key premise in AF ablation strategies. The aims of this thesis were to provide important original insights into both the electrical and structural remodeling responsible for atrial arrhythmias; and to the therapeutic implications for a procedure targeting this arrhythmia that is becoming increasingly performed in an expanding patient population. Hypertension is the most prevalent, independent and potentially modifiable risk factor for atrial fibrillation. In Chapter 2 conventional electrophysiologic studies were performed in patients with hypertension and no prior history of atrial fibrillation. The aim of this study was to gain insight into the underlying substrate before it is modified by the arrhythmia itself. This has been recognized as “atrial remodeling of a different sort”. In Chapter 3 we studied a population of patients with idiopathic pulmonary hypertension to study the atrial effects of pulmonary hypertension in the absence of the confounding effects of other disease states, such as obstructive sleep apnoea and chronic obstructive pulmonary disease. A better understanding of the atrial effects of pulmonary hypertension may help dissect out the relevant pathophysiologic factors responsible for the vulnerability to AF in these varied clinical conditions. In Chapter 4 the comparison of atrial substrate changes between patients with atrial fibrillation and atrial flutter are presented. Atrial fibrillation and atrial flutter are the most common sustained arrhythmias seen in clinical practice. Whilst there may be alternate expression of both AF and AFL in an individual patient, clinically one of these arrhythmias often predominates. Although it has been well recognized that both arrhythmias are associated with atrial substrate remodeling, to date there has been no direct comparison of atrial substrate changes in patients with AFL vs. AF. It has recently been recognized that atrial fibrillation is a risk factor for dementia in an aging population. However, the prevalence of neurocognitive abnormalities in a young low-risk population of AF patients is unknown. Chapter 5 describes the prevalence of neurocognitive abnormalities in patients with atrial fibrillation (paroxysmal and persistent atrial fibrillation); and an age-matched population of patients with supraventricular tachycardia, compared to normative controls. Our understanding of the efficacy and safety of catheter ablation is continuing to evolve as the procedure becomes more widespread and with longer follow up. Chapter 6 describes the change in neurocognitive outcomes after ablation for AF in patients with PAF and PeAF and in patients with ablation for supraventricular tachycardia, in comparison to patients with AF without ablation. The aetiology of neurocognitive abnormalities post AF ablation is likely to include cerebral microembolism. Chapter 7 describes the prevalence of cerebral microembolism occurring during AF ablation. Importantly, and a highly original finding, we report the composition of cerebral emboli (gaseous vs. solid) using a multi-frequency transcranial Doppler ultrasound. A significant part of this thesis details the formation of the atrial substrate that supports atrial fibrillation yet triggers from rapidly firing foci in the right and left atrium may be responsible for the initiation of focal atrial tachycardia. In Chapter 8, the incidence of tachycardia-induced cardiomyopathy among patients with focal atrial tachycardia is presented, with the electrophysiologic characteristics and the long-term clinical outcomes after successful catheter ablation. In summary this thesis provides insights into the atrial substrate responsible for arrhythmias that is critical in the development of further therapeutic advances. However, advances in therapy must include a comprehensive understanding of the safety profile. Further insights into these will lead to better clinical management and improvement in treatment strategies