Stellate ganglion modulation: An old therapy with a new twist for treatment of ventricular arrhythmias

The sympathetic nervous system has been shown to play a role in the initiation and maintenance of ventricular tachyarrhythmias (VT) and is associated with increased electrical heterogeneity and triggered activity [[1], [2], [3], [4]]. Hence, beta-adrenergic receptor blockers (β-blockers) remain first-line therapy for the treatment of ventricular arrhythmias and reduction of sudden cardiac death risk [5,6]. Despite β-blocker therapy, however, ventricular arrhythmias can recur. The underlying mechanisms for VT recurrence have been partially attributed to incomplete receptor blockade and, possibly, sympathetic co-transmitters, such as neuropeptide Y, which can also modulate ventricular action potential duration via their own specific receptors and have pro-arrhythmic effects [7]. As such, neuromodulation targeting the sympathetic nerves upstream of the heart, such as stellate ganglion block and cardiac sympathetic denervation, has been utilized for more complete sympathetic blockade in the management of refractory ventricular arrhythmias [8]. Consistent with this, two multi-center retrospective studies of 131 and 117 patients demonstrated the efficacy of stellate ganglion blockade for the treatment of ventricular arrhythmias, with additional data suggesting that continuous blockade may provide better efficacy than single bolus injections [[9], [10], [11]]. Left stellate ganglion blockade has been shown to increase ventricular action potential duration, effective refractory period, and ventricular fibrillation (VF) threshold and decrease arrhythmia inducibility in animal models [12]. As stellate ganglion blockade is limited by the half-life of anesthetics, cardiac sympathetic denervation (CSD) has been utilized as a more permanent option, typically consisting of left or bilateral surgical resection of the lower one-third to one-half of the stellate ganglia and the T2-T4 sympathetic ganglia. CSD has been reported to reduce the burden of VT in large animal models of chronic myocardial infarction and patients with structural heart disease, as well as those with long QT syndrome and catecholaminergic polymorphic ventricular tachycardia [[13], [14], [15], [16], [17], [18], [19]].

The present report by Narasimha and colleagues describes the management of a patient, with drug-refractory, PVC induced VF, using two separate neuromodulatory approaches [20]. The patient's electrical storm was initially stabilized with bilateral stellate ganglion block with 0.25 % ropivacaine followed by continuous catheter infusion, resulting in cessation of ectopy and VF for the following 18 hours. The patient then underwent bilateral radiofrequency (RF) ablation of the stellate ganglia under fluoroscopic guidance with a 22G RF needle, targeting the C7 and T1 levels of the paravertebral chain, with 3 ablation lesions per level and temperatures ranging from 50 to 70 °C, similar to a prior report [21]. No sustained VF was noted beyond this point, although PVCs with intermittently triggered non-sustained VF persisted. The patient subsequently underwent pace mapping and catheter ablation of PVCs, which were mapped to the left interventricular septum, possibly originating from Purkinje fibers. Post-ablation, the patient remained free of VT/VF for the subsequent 2.5 years of follow-up.

The case report confirms the importance of the sympathetic nervous system in initiating ventricular arrhythmias and highlights the role of stellate ganglion block as a treatment option for patients with refractory or incessant VT/VF. While CSD has been traditionally accomplished via surgical resection of the paravertebral chain, the authors herein apply RF ablation under fluoroscopic guidance at the C7/T1 level. The obvious advantage of RF ablation is its less invasive nature, compared to surgical CSD. However, it does also raise the concern for incomplete treatment, as it is difficult to visualize the stellate ganglia fluoroscopically. Targeting only the C7-T1 ganglia would also be expected to result in less complete sympathetic denervation, as cardiac-projecting postganglionic sympathetic efferent neurons in the T2, T3, and T4 sympathetic ganglia would potentially remain unaffected. This may have contributed to the differences in the efficacy of stellate ganglion blockade vs. RF ablation observed in this patient (who, after C7-T1 ganglia ablation and discontinuation of block, continued to have episodes of PVCs triggering non-sustained VF, resulting in the need for ventricular catheter ablation of PVCs). Notably, anesthetics, depending on the volume, can diffuse to the lower sympathetic chain by 2–3 levels, providing more complete blockade [22]. In addition, the long-term efficacy of RF stellate ganglion ablation as compared to surgical resection has not been evaluated and remains unclear. Whereas direct removal of the neuronal cell bodies via surgical CSD effectively prevents reinnervation of the myocardium and the resection of ganglia is confirmed histologically, RF ablation does not have a clear endpoint and can be subject to reinnervation, similar to renal denervation studies in animal models [23]. Thermal energy may also cause inflammation, which may initially activate any remaining postganglionic sympathetic neurons [24]. Therefore, additional studies evaluating the efficacy of RF stellate ganglion ablation are needed.

Nevertheless, the case report by Narasimha et al. adds to the body of evidence demonstrating the significant potential of stellate ganglia neuromodulation for treatment of ventricular arrhythmias. It also points to the important need for more permanent, non-invasive approaches to CSD in acutely ill patients, who may not be able to tolerate general anesthesia and single-lung inflation. While RF ablation may be considered, both long-term data and additional translational studies are needed to evaluate the endpoints for ablation, the potential for reinnervation, and the efficacy of this and other more non-invasive methods to modulate cardiac sympathetic tone for the treatment of VT/VF.

Declaration of competing interest

MV has shares in Nference and NeuCures Inc., and University of California, Los Angeles holds patents related to neuromodulatory therapies.