Atrial fibrillation: cardiac imaging, renal denervation and ablation strategies

© 2015 Dr. Alexander James Arthur McLellanAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with significant morbidity, mortality, and economic burden to the community. With expectations that AF incidence will increase, strategies are required to prevent AF occurrence or to improve the management of incident disease. Current anti-arrhythmic medications have limited efficacy and AF ablation procedures have imperfect success rates. The aim of this thesis is to identify strategies to improve the management of AF. Specifically, this thesis will focus on ablation strategies and the role of cardiac imaging in improving outcomes of AF ablation procedures, and will include an assessment of structural and electrical remodeling post renal denervation. Chapter 1 will summarize the current literature regarding AF mechanisms, atrial remodeling associated with AF, AF ablation strategies, and the utility of cardiac imaging in AF ablation procedures. Noting hypertension is the main modifiable risk factor for AF, this chapter will also summarize the literature regarding the interaction between hypertension and AF, and on the merits of renal denervation, which is a recently developed technology to achieve blood pressure reduction for patients with treatment resistant hypertension. Chapter 2 is the first human study to assess cardiac electrophysiological and structural remodeling associated with blood pressure reduction post renal denervation. In patients with treatment resistant hypertension, we performed detailed electrophysiology study and cardiac imaging before and 6 months post renal denervation; associated with blood pressure reduction there were significant improvements in cardiac electrophysiology and cardiac structure and function. This study suggests reducing blood pressure improves atrial electrophysiology and cardiac structure and function, and may in part explain the physiologic basis for reduced AF burden associated with improved blood pressure control. Chapters 3 and 4 are the first human studies to assess the impact of diffuse atrial (chapter 3) or ventricular (chapter 4) fibrosis on AF ablation outcomes. Diffuse fibrosis was assessed using novel post-contrast T1 mapping sequences on cardiac magnetic resonance imaging prior to AF ablation procedures in 112 patients (chapter 3) and 103 patients (chapter 4). Increased diffuse atrial or ventricular fibrosis were multivariate predictors of AF recurrence post procedure. These studies have identified novel prognostic indicators of altered cardiac substrate that may influence patient selection for AF ablation. Chapter 5 is the first human study describing a randomized controlled trial of a minimal or maximal ablation strategy for patients with paroxysmal AF. In this study 234 patients were randomized to a minimal (ipsilateral circumferential pulmonary vein isolation (CPVI) without ablation on the intervenous ridge) versus a maximal ablation strategy (ipsilateral CPVI with additional ablation across the intervenous ridge to achieve individual vein isolation). On intention to treat analysis there was no significant difference in freedom from AF between a minimal or maximal ablation strategy. However, 44% of minimal patients required ablation on the intervenous ridge to achieve electrical isolation, and was associated with significant increases in AF recurrence post procedure. This study provides insight into current AF ablation strategies regarding the implications of ablation on the intervenous ridge. Chapter 6 describes the impact of cardiac anatomy identified on pre-procedural cardiac imaging on AF ablation outcomes. This is the first human study to identify that in patients with paroxysmal AF, the presence of a left common pulmonary vein is associated with improved freedom from AF post procedure. Additionally we identified the novel finding that increased dimensions of the inter-venous ridge impacts AF ablation outcomes. This study may aid in prognosticating procedural success based on pulmonary vein anatomy as identified on pre-procedural cardiac imaging. Chapter 7 is a systematic review of the literature regarding the impact of adenosine/ adenosine-triphosphate (ATP) on dormant pulmonary vein (PV) reconnection after pulmonary vein isolation procedures. Pooling the results of 8 studies (from a search strategy that initially included 1027 references), we identified that using adenosine/ATP to assess for dormant PV reconnection resulted in improved outcomes compared to not using these medications. We also identified a non-significant trend for dormant PV reconnection elicited by adenosine/ATP to be associated with increased AF recurrence compared to no reconnection with adenosine/ATP. This systematic review has strengthened the platform for a randomized controlled trial assessing the role of adenosine in AF ablation procedures. Chapter 8 describes the largest series (165 patients) of posterior wall isolation (in addition to pulmonary vein isolation) for patients with persistent AF. Additionally this chapter describes the first report of posterior wall isolation with or without the use of adenosine to assess for dormant posterior wall conduction on arrhythmia recurrence post procedure. We identified adenosine could induce dormant conduction into the isolated posterior wall in 17% of patients. This study provides a platform for an appropriately powered randomized controlled trial of pulmonary vein isolation with or without posterior wall isolation for patients with persistent AF