Samantha Sublette MD

The cardiac autonomic nervous system contributes to the initiation and maintenance of AF through 1) parasympathetic-­ mediated shortening of action potential duration and the effective refractory period, 2) sympathetic-­ mediated calcium-loading, and promotion of delayed afterdepolarizations, and 3) sympathoadrenal discharge induced early afterdepolarizations in the PV and atrial myocardium. These effects are facilitated by the intrinsic cardiac ANS, which consists of clusters of autonomic neurons located within the ganglionated plexi, which contain afferent neurons from the atrial myocardium and the central ANS (ie, the extrinsic cardiac ANS), efferent adrenergic and cholinergic neurons, as well as an extensive network of interconnecting neurons. Previous studies evaluating the neuromodulation effect of PVI postulated that the alterations in GP function following ablation were transient (typically lasting <6 months). However, this was a misconception likely related to historical reliance on intermittent non-invasive assessment performed at limited timepoints on follow-up. We previously demonstrated that there is a significant decrease in HRV (measured as SDANN), and significant increases in daytime and nighttime heart rates (bit.ly/4fnqj08), changes which are dynamic over the first 3 months following ablation and persist for 3 years or more post-­ ablation (bit.ly/4hzalBj). Importantly, patients free of arrhythmia recurrence had significant differences in autonomic parameters. But the next question, is what happens to the autonomic system when randomised to ablation or AAD therapy (e.g. were the previously described effects related to the transition between AAD to ablation, or is there an independent effect)? In the EARLY-AF population (RCT of ablation vs. medical therapy with continuous rhythm monitoring) we observed: 1. Patients randomised to ablation experienced a significant increase in DHR and NHR, and a corresponding significant decrease in HRV 2. In contrast, no significant changes in heart rates nor HRV were observed with pharmacologic rhythm control. 3. Patients who crossed over from AAD therapy to catheter cryoablation (eg acted as their own control) exhibited alterations in heart rates and HRV consistent with the treatment received (third image). PVI results in significant sustained changes in the heart rate parameters related to autonomic function that are consistent with protective antiarrhythmic effects. These changes were not observed in patients treated with AAD therapy (bit.ly/4bdMbZm). References: Cryo vs. RF ablation - 1 year outcomes - ahajournals.org/doi/10.1161/… - 3 year outcomes - jacc.org/doi/10.1016/j.jacep… Ablation vs Medical Therapy - authors.elsevier.com/a/1nRjg…