Fractionated Atrial Electrograms Identify Sites of Autonomic Responses During Pulmonary Vein Isolation: Insights for Cardioneuroablation

Figures

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  FIGURE 1. Definitions and schematic of fractionation mapping algorithm parameters: Maximum Width: maximum time allowed from the start of deflection until its return to isoelectric line to be counted as one deflection for the calculation of fractionation. Amplitude threshold: (Roving sensitivity) The minimum voltage amplitude required for a deflection to be counted as a fractionation. Set to just above the baseline noise to eliminate any EGM noise from being mistaken as a fractionation. Refractory: the minimum time allowed from start of one deflection until a second deflection may be counted. This parameter acts as a blanking period to prevent new detections (double counting) for a specified time after detection has occurred [7].

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  FIGURE 2. Bootstrap‐adjusted sensitivity and specificity across all evaluated fractionation mapping configurations. Sensitivity (left) and specificity (right) are shown with 95% bootstrap confidence intervals obtained using patient‐level bootstrap resampling to account for intra‐patient clustering. Configurations are ordered by decreasing sensitivity. Dotted vertical blue lines indicate the 95% confidence interval of the most sensitive configuration (#6: Width 15 ms—Refractory period 25 ms—Roving sensitivity 0.05 mV). All other configurations have confidence intervals that lie entirely within this interval, except configurations #26 (10–30–0.15), #19 (5–20–0.15), #25 (5–30–0.15), and the empirical anatomical approach. Configuration parameters are defined as follows: Width (5, 10, or 15 ms), refractory period (20, 25, or 30 ms), and roving sensitivity (0.05, 0.10, or 0.15 mV). Raw point‐by‐point estimates are provided in Table S2.

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  FIGURE 3. Representative case illustrating the effect of automated fractionation mapping settings on the spatial distribution of fractionated atrial EGMs during cardioneuroablation. Three‐dimensional electroanatomic maps of the left atrium were obtained with EnSite NavX Cardiac Mapping System (St. Jude Medical, Abbott, Sylmar, CA, USA) in the same patient and projection (antero‐posterior view). In all panels, white areas represent regions classified by the automated algorithm as fractionated according to the selected software parameters, whereas purple areas represent regions with absent or low fractionation. Multicolored borders indicate the transition across the fractionation color scale generated by the mapping system. White areas: Fractionated EGM; Purple areas: absent/low fractionation; White spheres: autonomic response sites during RF delivery; Pink/red spheres: RF lesions. Panel A: Fractionation map obtained with configuration #6, defined by a signal width of 15 ms, refractoriness of 25 ms, and amplitude threshold of 0.05 mV. This configuration showed the highest sensitivity in the primary AF cohort and identified a broader distribution of fractionated regions. Panel B:…

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  FIGURE 4. Heatmap comparing sensitivity and specificity. Heatmaps display bootstrap‐adjusted sensitivity (left panels) and specificity (right panels) according to combinations of width, refractory period, and roving sensitivity parameters. Warmer colors indicate higher performance values. Across parameter combinations, lower amplitude thresholds and intermediate refractory periods were consistently associated with higher sensitivity, whereas increasing refractory period and amplitude threshold progressively shifted performance toward higher specificity at the expense of sensitivity.

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  FIGURE 5. Spatial distribution of sites of autonomic response. The distribution of autonomic responses observed during RF delivery is displayed according to pulmonary vein antral region. Higher response frequencies were observed predominantly within left anterior regions and the right superior‐anterior region, corresponding anatomically to areas commonly associated with the left lateral/Marshall‐related GP and the right anterior GP. In contrast, posterior and inferior right‐sided regions demonstrated substantially lower response frequencies.

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  FIGURE 6. Programmable EGM parameters and autonomic responses during ablation. Conceptual overview of the study design and physiological rationale underlying programmable electrogram fractionation mapping during ablation. In the primary AF cohort, 27 predefined combinations of signal width, refractory period, and roving sensitivity were systematically evaluated across 870 ablation sites during PVI to identify electrogram parameter profiles associated with autonomic responses. The central panel illustrates how programmable fractionation parameters influence electrogram classification and mapping sensitivity. In an independent exploratory CNA cohort, the optimized high‐sensitivity configuration identified in the AF cohort was retrospectively evaluated off‐line, demonstrating preservation of the fractionation–autonomic response association. Overall, the figure summarizes a reproducible methodological framework for identifying electrophysiological signatures associated with autonomic‐responsive atrial tissue.