Left Stellate Ganglion Pulsed Radiofrequency Suppresses Ischemic Ventricular Arrhythmias: A Translational Study.

Background

Cardiac sympathetic hyperactivity originating from the left stellate ganglion (LSG) drives ischemic ventricular arrhythmias (VAs). Stellate ganglion block provides only transient relief, whereas surgical denervation is invasive and irreversible. A minimally invasive approach with potentially sustained effects is needed.

Objectives

This study sought to investigate whether pulsed radiofrequency (PRF) of the LSG-a nonthermal neuromodulatory technique-safely suppresses ischemic VAs, and to characterize its mechanism using integrated neural and cardiac transcriptomics.

Methods

Safety was first assessed in healthy rats (n = 15) randomized to control, LSG-PRF (42 °C, 2 Hz, 20 milliseconds), or surgical LSG excision. In a rat myocardial infarction (MI) model (n = 24; Sham, MI, MI + PRF), cardiac sympathetic nerve activity, programmed electrical stimulation, echocardiography, and histology were evaluated, complemented by bulk RNA-seq of the LSG and single-cell RNA-seq of cardiac tissue. Translational feasibility was tested in 4 patients with drug-refractory electrical storm using ultrasound-guided LSG-PRF.

Results

In contrast to LSG excision, PRF produced only transient Horner's syndrome and did not cause hypotension. In MI rats, PRF reduced cardiac sympathetic nerve activity, attenuated ventricular tachycardia/ventricular fibrillation inducibility and duration on programmed stimulation, lowered serum norepinephrine and angiotensin II, improved left ventricular function, and reduced myocardial fibrosis. LSG transcriptomics showed down-regulation of inflammation- and sprouting-related genes including S100a9 and Ngf. Single-cell analysis of the infarcted heart revealed attenuation of a proinflammatory Grik2+ Schwann cell subset, with computationally inferred reductions in neuro-immune signaling. In all 4 patients, no sustained ventricular tachycardia recurrence was observed during a median follow-up of 12 months.

Conclusions

LSG-PRF is a minimally invasive neuromodulatory strategy associated with suppression of sympathetic hyperactivity and post-MI VAs, accompanied by attenuated ganglionic inflammation and modulated cardiac neuro-immune signaling. Preliminary clinical experience supports feasibility and warrants prospective trials.