Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. This pathology affects more than 750,000 persons in France. Radiofrequency (RF) endocardial ablation is performed to treat this disease and involves the generation of transmural thermal lesions, to isolate electrically the pulmonary veins (PV) from the left atrium. The technique is, however, invasive and has a limited efficiency, especially for ensuring transmurality which requires a perfect contact between the RF probe and cardiac tissues. High Intensity Focused Ultrasound (HIFU) allows the creation of precise thermal lesions, deep within biological tissues. A transesophageal HIFU approach could provide a minimally-invasive alternative for AF treatment, since deep transmural lesions could be generated at distance from the HIFU probe. In this work, an ultrasound-guided transesophageal applicator has been developed for AF treatment. The HIFU transducer, embedding a transesophageal echocardiography (TEE) probe, can focus the acoustic beam from 17 to 55 mm axially and generate a surface acoustic intensity up to 12 W•cm-2. A complex treatment plan, the HIFU Mini-Maze (HIFUMM), was successfully simulated on a realistic anatomical human model. Transesophageal HIFU lesions were induced experimentally in static myocardium, under ex vivo configurations reflecting an increasing complexity in anatomical and physiological conditions. Investigations conducted on shear wave elastography confirmed the feasibility of using TEE to control the formation of HIFU lesions. Finally, in vivo experiments in a porcine model allowed validating the treatment procedure by inducing biological damages in beating heart