Atrial fibrillation (AF) leads to an irregular and rapid heart rate, and is the most common heart rhythm disturbance. One in five strokes in people aged over 60 years is caused by AF. AF contributes significantly to the national health burden. Better understanding of atrial structural changes responsible for sustaining AF and the most effective strategies for terminating AF by modifying this structure will lead to improved treatment outcomes. The proposed studies will be carried out by a world-leading international team using explanted intact human hearts and employ novel approaches including high resolution panoramic functional and structural mapping, 3D quantitative analysis and computer simulation studies. This proposal will provide an integrated computer framework not only for systematic interpretation of experimental data, but also for planning the optimised patient-specific treatment. Subsequent experimental and in-vivo patient studies will validate the proposed treatment. The research will impact clinical practice worldwide.