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Research Project: Conduction of Action Potentials through Gaps Between RF Ablation Lesions

 

Principle Investigator: Felipe Aguel

Percutanous ablation of the left atrium is increasingly used clinically to isolate the pulmonary veins as a treatment for atrial fibrillation. Currently, the most commonly used approach is to generate a series of spot lesions that are connected to encircle –and isolate– the pulmonary veins. However, it is postulated that failure to connect the spot lesions may leave isthmuses through which ectopic beats originating in the pulmonary veins may initiate and help sustain episodes of atrial fibrillation. In at least two circumstances patients are treated with pharmacologic agents to alter the electrophysiology of the atria following an unsuccessful ablation procedure: 1) to manage post-ablation atrial fibrillation by terminating action potential propagation through gaps and 2) to identify viable gaps of cardiac tissue within an incomplete ablation “line” during a subsequent ablation procedure by facilitating action potential propagation through gaps. Recurrence of atrial fibrillation following ablative isolation of pulmonary veins is often manageable with an anti-arrhythmic drug regimen that was unsuccessful prior to the ablative procedure. One possible mechanism of action of the postprocedure drug regimen is the ability of the antiarrhythmic drugs to inhibit propagation through the remaining isthmus between spot ablation lesions. We have implemented a well controlled model of ablation lesions that leave a remaining isthmus, and we propose to characterize the lesion and isthmus geometries likely to ineffectively isolate the pulmonary veins as well as the mechanism of action of the drugs that inhibit propagation through those isthmuses. Patients often undergo multiple ablation procedures because the index procedure failed to completely and permanently isolate the pulmonary vein triggers of atrial fibrillation, despite the fact that it is clinical practice to check for isolation at the end of an ablation procedure. In many cases of recurrence, it is difficult to identify the location of reconnection between the pulmonary veins and the rest of the left atrium. In these cases, drugs like adenosine and isoproterenol are used to facilitate conduction through gaps of viable tissue in the ablation line, in order to identify and ablate the gaps during subsequent procedures. It has been shown in small clinical studies that using adenosine while verifying electrical isolation at the end of the index ablation procedure improves the long-term success rate of the procedure. However, the mechanism of action remains unknown, and as a result the procedure is not widely accepted. We propose to elucidate the mechanisms by which these drugs promote propagation through gaps of viable tissue, and to investigate additional pharmacologic agents used for this purpose.