Introduction: The cardiac autonomic nervous system has a critical role in the onset and maintenance of atrial fibrillation (AF). The ganglionated plexi, as well as the pulmonary vein (PV) ostia, are richly innervated by both the sympathetic and parasympathetic autonomic systems. Consequently, it is not a surprise that the parasympathetic tone is acutely modified during and after the second-generation cryoballoon ablation (CB-A), which has become the most prevalent invasive technique in the treatment of paroxysmal AF. Nevert-heless, a detailed analysis of the parasympathetic de-nervation after ablation of the right or left-sided PV is still lacking.

Objective: We sought to evaluate the contribution of the right and left sided PVs isolation in the acute cardiac vagal denervation after CB-A by means of external cardiac vagal stimulation (ECVS).

Methods: Twenty consecutive patients with drug-re-fractory symptomatic PAF by means of CB-A ablation, in which ECVS was performed before, during and af-ter ablation were included in this study. The ECVS was performed by positioning a quadripolar catheter in the right internal jugular vein via transfemoral route and electrical stimulation of the vagal nerve. In the first ten patients, the ablation was performed clockwise starting from the LSPV with vagal response measurement by ECVS after the left sided PVs isolation. In the following ten patients, the ablation was performed counterclo-ckwise starting from RSPV with vagal response mea-surement by ECVS after the right sided PV isolation.

Results: The ECVS performed pre-ablation provoked cardioinhibitory responses in all cases with mean pause duration of 11053.6 ± 3249.6 ms, while the ECVS per-formed post-ablation provoked cardioinhibitory res-ponses with a mean pause duration of 1372.1 ± 911.3 ms (p< 0.0001). In the group started from the LSPV, the vagal response after the ablation of the left-sided PVs was reduced by 23.19 % when compared to baseli-ne response, to a mean of 8490.2 ± 1040 ms (p= 0.01). Noteworthy, in the group started from the RSPV, the vagal response after the ablation of the right-sided PVs was reduced by 91.8% when compared to baseline res-ponse, to a mean of 902.7 ± 271.04 ms (p< 0.001). The vagal response post-ablation was not statistically diffe-rent among the two groups.

Conclusions: Although not directly targeting the ganglion plexuses, AF treatment with the CB-A causes a significant acute parasympathetic denervation. The right sided PVs isolation showed to be associated with the most extensive parasympathetic denervation. This knowledge might also be useful to understand the role of the vagal tone in different heart diseases.