Investigation of the anatomical, morphological and electrical characteristics of the left atrial appendage and the impact of left atrial appendage electrical isolation and occlusion on the treatment of atrial fibrillation
Creators: name: Panikker, Sandeep
Publisher: name: Imperial College London
Year: 2016

description: While success rates of catheter ablation for paroxysmal atrial fibrillation (AF) are good, the optimal treatment for persistent AF remains uncertain. Pulmonary vein isolation is a cornerstone in the treatment of persistent AF. However, extra pulmonary vein sites are also responsible for the initiation and maintenance of AF of which the left atrial appendage (LAA) has been identified as having a significant role. Electrical isolation of the LAA may improve freedom from atrial arrhythmias, though results in a high risk of thromboembolism due to a non-contractile appendage and may increase the risk of perforation if ablation is performed at areas of thin tissue. A pre-clinical canine study was conducted to evaluate the safety and feasibility of conventional pulmonary vein isolation with concomitant LAA electrical isolation and device occlusion. Histological analysis gave valuable information about regions of the LAA ostium that were more challenging to ablate and demonstrated that the procedure was both feasible and safe. Following on from this study, a translational, pilot study of conventional AF ablation with concomitant LAA electrical isolation and occlusion was designed and conducted to evaluate the feasibility and safety of this procedure in humans with longstanding persistent AF when compared to a control group undergoing conventional AF ablation only. The primary efficacy end point was successful LAA electric isolation and occlusion and primary safety end point was the absence of any major procedure-related complication or thromboembolic event during follow-up. The secondary end points included single-procedure atrial arrhythmia–free survival, AF-free survival, and atrial arrhythmia– free survival time, left atrial (LA) size and change in AFEQT quality of life score over the 12 month follow-up period. Safety and feasibility were demonstrated. Study patients experienced significantly higher freedom from AF recurrences (95% vs 63%, p=0.036) than control patients. There was also a trend to higher freedom from AF or atrial tachyarrhythmia, though this did not reach statistical significance (60% vs 40%, p=0.17). A high rate of acute LAA reconnection (85%) was observed during the initial ablation procedure with most seen at the anterior and superior margins of the LAA ostium. Histological analysis of cadaveric patient samples matched to the study cohort for left atrial size and AF duration demonstrated that the regions of significantly thicker tissue at the LA-LAA junction corresponded to the sites where acute reconnection was most commonly seen. To further investigate these findings, a novel algorithm was designed to accurately measure the thickness of the LA-LAA junction from the pre-procedural CT scans of the study patients. Measured wall thicknesses correlated well with clinically observed acute reconnection sites and with histological measurements. This provided a robust, semi-automated method to accurately measure atrial wall thicknesses, which may ultimately help guide ablation. Percutaneous LAA closure (LAAC) carries a high upfront cost when compared to existing pharmacological therapies for stroke prevention in non-valvular AF. It is important to quantify the clinical benefits and costs of this procedure to aid appropriate allocation of limited healthcare resources. A detailed UK perspective cost impact analysis was performed utilising data from randomised controlled data and real-world experience of LAAC relative to oral anticoagulation. LAAC may offer substantial savings compared with current oral therapies. Savings are most evident in patients at higher risk of stroke and those unsuitable for anticoagulation.