Vagal influence on atrial electrograms: differentiating structural Vs. functional fragmentation in ganglionated plexi regions

Background Ganglionated plexi (GPs) are the primary target of ablative therapies for neurally mediated syncope (NMS); however, the optimal method for their endocardial localization remains unclear. This study analyzed bipolar atrial electrograms (EGMs) and their response to a vagolytic agent to elucidate their relationship with the parasympathetic network. Methods and aim High-density right atrial mapping was performed before and after 2 mg atropine in healthy patients without structural heart disease undergoing electrophysiological study for standard indications. Offline analysis compared pre- and post-atropine maps, focusing on fragmentation patterns and spectral analysis. Results The study included 13 patients (mean age: 34±12 years, 9 males). Baseline maps exhibited a consistent fragmentation pattern in the posterior-septal wall, reflecting anatomical right GPs distribution. No difference in density of points between the after and before map was detected (8521.7 ± 1517.1 vs 8512.5 ± 1085.5, p=0.97, respectively). Three primary areas were identified in the supero-(A), mid-(B), and infero-posterior-(C) regions (Figure, Upper Section). Fragmentation of EGMs was found to increase from the periphery toward the core of each area. In fact, the fragmentation pattern was consistent across all analyzed GPs areas: a centrally located, rounded high-fragmentation area (≥6 deflections) was surrounded by a low-fragmentation area (≥4 deflections), which had a more heterogeneous shape, with a transition zone (≥5 deflections) in between. Atropine significantly reduced fractionated areas (p<0.001 for A and C, p<0.05 for B, Figure, Upper and Central Section). External areas exhibited "functional" fragmentation, sensitive to vagal output, whereas central cores displayed "structural" fragmentation, resistant to vagolysis. Conclusion Fragmentation of atrial EGMs is a dynamic property, related to parasympathetic output. Standard fragmentation criteria may overestimate GPs areas. Regarding the catheter-based ablation for the treatment of NMS, these results could suggest a more selective approach on the central core of GPs, potentially reducing procedural risks and improving long-term outcomes.