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Title: A mechanistic basis for improving outcomes from paroxysmal atrial fibrillation ablation
Author: Malcolme-Lawes, Louisa
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Pulmonary vein isolation (PVI) is a recommended treatment for drug-refractory paroxysmal atrial fibrillation. However, success rates remain around 50-70% for a single procedure despite advances in mapping and ablation technologies. PV reconnection is found in almost all patients with AF recurrence and therefore improving lesion durability is the focus of technological developments such as robotic manipulation. We demonstrated that robotic-assistance improves catheter stability compared to manual catheter guidance during AF ablation, resulting in greater electrogram attenuation at matched RF settings. However, this has not translated into improved outcomes in recent non-randomised trials, which may reflect that we only studied acute lesions. Several recent studies suggest that late-gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) can be used for studying chronic ablation lesions. We developed an automated LGE-CMR method to detect left atrial ablation scar and validated the technique by comparing co-located electrogram amplitude. A significant correlation between scar and endocardial low voltage was demonstrated. Interestingly, higher levels of pre-existing atrial scar were associated with lower success rates following ablation. Furthermore, whilst veins found to be isolated at the redo procedure had greater levels of ostial scar than reconnected veins, there was no difference in the amount of ostial scarring or the number of circumferentially scarred veins between patients with and without AF recurrence. This finding is in keeping with invasive studies which suggest that there is a significant degree of reconnection in asymptomatic patients and highlights inconsistencies in our understanding of PV mediated ectopy. It has been suggested that PVI inadvertently damages upstream regulators such as the atrial ganglionated plexi (GP) of the intrinsic cardiac autonomic nervous system and animal studies indicate that these may be potential targets for ablation to prevent AF. Continuous high frequency stimulation (HFS) of GPs produces AV block and this phenomenon has been used to identify and ablate the GPs as putative autonomic triggers for PV ectopy. However, animal studies have revealed a complex network of autonomic connections and these have not been investigated in detail in humans. We found that the right lower GP is the final common pathway to the AV node and must remain intact if all other GPs are to be identified and ablated. Heart rate variability has been suggested as a potential endpoint for autonomic modification. Using a novel intraprocedural, short-segment HRV tool, we found that the reduction in HRV following AF ablation occurs only after ablation of the right upper GP and therefore does not reflect the inputs from any other left atrial GP, precluding its use as an endpoint for left atrial denervation. Furthermore, it would seem logical to target the parts of the network that trigger PV ectopy rather than targeting GP sites that produce effects at the sinus node and AV node. We developed a technique to identify sites initiating ectopic triggers and found that the response could be abolished either by achieving PVI or by targeted RF ablation to the site. This raises the possibility of targeted autonomic denervation of culprit sites of atrial ectopy as an alternative strategy to PVI. These findings should now be applied prospectively to assess their impact on outcomes from AF ablation.
Supervisor: Kanagaratnam, Prapa ; Rueckert, Daniel Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral