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Determinants of new wavefront locations in cholinergic atrial fibrillation

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Caroline H. Roney, Fu Siong Ng, Michael T. Debney, Christian Eichhorn, Arun Nachiappan, Rasheda A. Chowdhury, Norman A Qureshi, Chris D Cantwell, Jennifer H Tweedy, Steven A. Niederer, Nicholas S Peters, Edward J. Vigmond

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Abstract

Aims: Atrial fibrillation (AF) wavefront dynamics are complex and difficult to interpret, contributing to uncertainty about the mechanisms that maintain AF. We aimed to investigate the interplay between rotors, wavelets and focal sources during fibrillation.
Methods: Arrhythmia wavefront dynamics were analysed for four optically mapped canine cholinergic AF preparations. A bilayer computer model was tuned to experimental preparations, and varied to have 1) fibrosis in both layers or the epicardium only, 2) different spatial acetylcholine distributions, 3) different intrinsic APD between layers, and 4) varied interlayer connectivity. Phase singularities (PS) were identified and tracked over time to identify rotational drivers. New focal wavefronts were identified using phase contours. PS density and new wavefront locations were calculated during AF. Results: There was a single dominant mechanism for sustaining AF in each of the preparations, either a rotational driver or repetitive new focal wavefronts. High-density PS sites existed preferentially around the pulmonary vein junction. Three of the four preparations exhibited stable preferential sites of new wavefronts. Computational simulations predict that only a small number of connections are functionally important in sustaining AF, with new wavefront locations determined by the interplay between fibrosis distribution, acetylcholine concentration and heterogeneity in repolarisation within layers. Conclusions: We were able to identify preferential sites of new wavefront initiation and rotational activity, in order to determine the mechanisms sustaining AF. Electrical measurements should be interpreted differently according to whether they are endocardial or epicardial recordings.

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