Chronic atrial fibrillation, affecting more than 2 million patients in the US and causing 15 percent of all strokes, currently presents one of the greatest treatment challenges in cardiac electrophysiology. Atrial fibrillation is accompanied by both clinically apparent alterations in overall atrial anatomy such as pronounced dilatation, and experimentally measurable changes in tissue and cellular electrophysiology including changes in conduction velocity and restitution properties. The combination of anatomic and electrophysiologic abnormalities has been suggested as a reason that atrial fibrillation occurs and is perpetuated. It is our hypothesis that the anatomical structure of diseased atria is the dominant factor in allowing normally self-terminating atrial fibrillation to become sustained, while cellular electrophysiology plays a more limited role. To test this hypothesis, we will develop computer models of both normal and diseased atrial structure and cell physiology and simulate atrial fibrillation to determine whether diseased anatomy, remodeled electrophysiology, or both are necessary to support sustained atrial fibrillation. This research should lead to future animal experiments and ultimately clinical applications. If altered anatomy is indeed a primary mechanism that allows atrial fibrillation to become sustained, the anticipated clinical relevance to treatments such as radiofrequency catheter ablation is significant, in that it may be possible to develop more effective ablation patterns by taking into account the anatomical details of individual patients. ? ?
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