During the past four years, radiofrequency catheter ablation (RFCA) has replaced surgery as the treatment of choice for medically refractory cardiac arrhythmias. Indeed, RFCA has been so safe and effective in ablating supraventricular tachycardia due to the Wolff-Parkinson-White syndrome and AV node reentry that it has actually supplanted medicine as their treatment of choice. Unfortunately, while RFCA has shown early promise in ablating atrial flutter, it has not yet proven effective in the treatment of atrial fibrillation (AF), the most common of all cardiac arrhythmias. During the past 15 years, we have developed several clinically-relevant animal models and multi-point computerized mapping systems capable of elucidating the complex electrophysiologic basis of AF. These studies provided the knowledge essential to the development of a safe and effective surgical treatment for medically refractory AF. This surgical technique, the Maze Procedure, was designed to: 1) cure AF, 2) restore AV synchrony, and 3) restore atrial transport function. The Maze Procedure was first applied clinically in 1987 and has now been performed by the investigators in over 140 patients with ablation of AF, restoration of AV synchrony, and preservation of atrial transport function in 99% of all patients. Similar results have now been obtained in over 300 other patients world-wide. The original Maze-I Procedure has undergone two modifications, culminating in the Maze-III Procedure which has been used exclusively in the past 90 patients. In the present renewal proposal, we describe our plans for converting the open heart Maze-III Procedure to a closed-heart Maze-V Procedure. The Maze-IV Procedure will be performed by opening the chest and placing multiple linear cryolesions on the atria with specially designed cryoprobes. The Maze-V Procedure will be performed using a combination of trans-vascular radiofrequency catheters and trans-pericardial thoracoscopic instruments. Anecdotal reports containing marginal documentation of successful closed-chest radiofrequency ablation of "atrial fibrillation" have now begun to appear. Similar reports surfaced several years ago regarding sudden surgical cures for AF, none of which proved successful because of an inadequate scientific basis underlying the espoused techniques. Similar problems now face these anecdotal reports using RFCA for AF. We believe that the development of a closed-chest cure for AF will not occur by serendipity but rather will follow a methodical, focused and intensive evaluation of well-conceived approaches based on existing and new knowledge and on the experience gained from previous surgical techniques. Our experience in elucidating the electrophysiologic basis of AF and with developing, testing, and applying a surgical treatment to cure it provides the type of foundation needed for the development of safe, less invasive techniques for the treatment of AF, ultimately culminating in a closed-chest procedure.