High-frequency stimulation
Animal experiments demonstrated that electrical stimulation of left atrial sites areas caused 2 types of response in different parts of the LA: a vagal response (VR), defined as a significant prolongation of the PR and/or RR intervals, and a normal response characterized by the absence of any effect or nonsignificant changes on the PR or RR intervals (55). Theoretically, demonstration of a positive VR differentiates autonomic innervation sites than normal atrial myocardium. Because each epicardiac ganglia contains both parasympathetic and sympathetic neural elements, response to HFS may change according to duration of application. While shorter applications stimulate parasympathetic fibers, if HFS is delivered more than 2–5 seconds, sympathetic fibers may be stimulated, which may subsequently mitigate the parasympathetic response (55, 59).
According to the sites exhibiting a VR to HFS and fractionated electrogram characteristics during AF, 5 major epicardiac GPs were identified by Nakagawa et al (55): 1) the right anterior GP ; 2)the right inferior GP ; 3) the left superior GP ; 4)the left inferior GP ; and 5) the Marshall ligament GP . Figure 5 demonstrates the anatomical distribution of these 5 GPs (55). Interestingly, in spite of using a quite similar HFS protocol, Kim et al (60) found a more scattered distribution although the VR sites were located mainly on the posterior wall of the LA. We believe that one reason for this discrepancy may be that HFS may stimulate not only epicardial ganglia but also nerves that extend from epicardial ganglia towards the atrial regions. Indeed, despite its strong theoretical background, a HFS-based strategy has not demonstrated an advantage over empirical anatomic ablation in patients with AF as well as VVS (61, 62).