Methodological Evaluation of High-Density Fractionation Mapping Parameters for Cardioneuroablation: A Pilot Derivation and Validation Study

Purpose Cardioneuroablation (CNA) targets atrial ganglionated plexuses to treat vagally mediated bradyarrhythmias. Automated electrogram fractionation mapping has been proposed as a surrogate tool for ganglionated plexus localization; however, optimal software parameter settings for real-time use remain undefined. This study was designed as a methodological pilot investigation. Methods Data from a total of 28 patients were analyzed, including a prospective derivation cohort of 12 patients undergoing atrial fibrillation ablation in sinus rhythm and an independent validation cohort of 14 patients undergoing CNA. Using high-density electroanatomical mapping, three predefined values were tested for each fractionation parameter—signal width, refractoriness, and amplitude threshold—yielding 27 automated configurations. A purely anatomical localization strategy was also assessed, resulting in 28 total mapping configurations. All configurations were systematically generated for each patient in the derivation cohort, producing 336 fractionation maps and 870 ablation sites. Parasympathetic response during radiofrequency ablation was defined as an RR interval change > 10%, transient atrioventricular block, or sinus pause/asystole. The most sensitive configuration was subsequently applied to the validation cohort (614 ablation sites). Results In the derivation cohort, 25 of 27 automated parameter combinations showed significant association with parasympathetic response. The configuration with signal width 15 ms, refractoriness 25 ms, and amplitude threshold 0.05 mV was selected as the most sensitive. When applied to the validation cohort, this predefined configuration demonstrated preserved diagnostic performance, with a sensitivity of 74.1%, specificity of 73.9%, and negative predictive value of 94.9%. Fractionation-guided localization outperformed a purely anatomical approach. Conclusions This pilot study provides a reproducible methodological framework for evaluating automated fractionation mapping parameters associated with parasympathetic responses during CNA. These exploratory findings warrant prospective validation in larger cohorts.