Acute physiological responses to stimulation before and after thermal ablation of subclavian ansae bundle for neuromodulation of bilateral efferent sympathetic pathways

Background Dysregulated sympathetic reflex activation has been implicated in cardiac arrhythmogenesis. Sympathetic reflex pathways involve the stellate ganglia and the subclavian ansae (SA), a nerve bundle that wraps around the subclavian artery before connecting to the middle cervical ganglia and thoracic cardiopulmonary nerves. The SA offers a nodal intervention point to target deranged cardiac sympathetic overactivation. Electrical stimulation of the SA increases arterial blood pressure (ABP) and heart rate, confirming SA-mediated sympathetic activation. Stellate block and surgical stellate ganglionectomy modulate the efferent sympathetic pathway to the CV system, reducing ventricular arrhythmias in clinical settings; however, these procedures are either temporary or invasive. We evaluated the feasibility and safety of a catheter-based procedure designed to attenuate sympathetic reflex activation via transarterial thermal ablation of the SA. Methods The study was conducted in normal domestic swine (n=10, 60-75 kg). A custom quadripolar catheter (SymKardia, Inc., Minneapolis, USA) was sequentially placed via standard femoral access into the right and left subclavian arteries and deployed immediately proximal to the SA. Bipolar stimulation trains (5-35 mA, 10 Hz, 1000 µs) were delivered to evoke a CV response (CVR), assessed through continuously monitored heart rate and ABP. After CVR confirmation, radiofrequency (RF) ablation energy was delivered to create a series of extravascular lesions. Ablation was confirmed by post-ablation stimulation delivered to the same sites at same and/or higher dose to test reduction of CVR. The animals were sacrificed and tissue was harvested for histological analyses. Results In all 10 animals, bilateral catheter positioning and deployment was safe and successful. Pre-ablation CVR was highly dependent on stimulation parameters, confirming sympathetic activation. Across all animals, a total of 43 ablation lesions were created in the right (n=26) and left (n=17) subclavian arteries. Post-ablation ABP changes during stimulation were reduced by 55.6% (from 8.3 ± 1.8% pre-ablation to 3.9 ± 1.1%, p<0.005). In all 10 animals, extravascular lesions were observed at the stimulation/ablation sites, with a diameter of 2.5 to 5.0 mm. Histology showed an absence of thrombus or any significant thermal damage to the artery wall in all 20 vessels analyzed, with clear evidence of extravascular denervation. Conclusion This preclinical study confirms the SA as the nodal intervention point to target cardiac sympathetic signaling and provides direct evidence that bilateral central sympathetic denervation of the subclavian ansae is feasible, with no acute adverse events, and results in an acute attenuation of stimulation-related CVR. Further research is required to demonstrate the chronic safety, feasibility, and effectiveness of this therapy.