The procedure of catheter ablation for the treatment of drug resistant atrial fibrillation (AF) has evolved but still relies on lesion sets intended to isolate areas of focal firing, mainly the myocardial sleeves of the pulmonary veins (PVs), from the rest of the atria. However the success rates for this procedure have varied inversely with the type of AF. At best success rates have been 20 to 30% below that of other catheter ablation procedures for Wolff-Parkinson-White syndrome, atrioventricular junctional re-entrant tachycardia and atrial flutter. Basic and clinical evidence has emerged suggesting a critical role of the ganglionated plexi (GP) at the PV-atrial junctions in the initiation and maintenance of the focal form of AF. At present the highest success rates have been obtained with the combination of PV isolation and GP ablation both as catheter ablation or minimally invasive surgical procedures. Various lines of evidence from earlier and more recent reports provide that both neurally based and myocardially based forms of AF can separately dominate or coexist within the context of atrial remodeling. Future studies are focusing on non-pharmacological, non-ablative approaches for the prevention and treatment of AF in order to avoid the substantive complications of both these regimens. 1. Historical Background: From Bedside to Bench The examination of a patient with chest palpitations and an irregular and rapid pulse was more definitively diagnosed and designated as auricular fibrillation with the advent of the electrocardiogram at the beginning of the 20th century. This clinical observation engendered an ongoing polemic for many subsequent decades regarding the mechanism underlying this most common disordered cardiac rhythm. Essentially two schools of thought developed, each with its chief proponents, each based on accumulated experimental evidence, which were apparently contradictory to one another. Specifically, Scherf and his associates [1, 2] promulgated the focal theory of atrial fibrillation (AF) by demonstrating that substances, such as aconitine [1] or acetylcholine applied to the atrial appendage or to the area of the sinus/AV node, [2] could induce a rapid auricular tachycardia or auricular fibrillation, respectively. Isolation of the appendage or local cooling was consistently able to suppress the tachyarrhythmia thereby promoting the conclusion that AF was focal. On the other hand, initial studies by Moe [3] provided strong evidence for multiple wavelets (reentrant circuits) occupying the atria during AF induced by triggering atrial
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