Stellate ganglion blockade for the management of ventricular arrhythmia storm

This editorial refers to ‘Electrical storm treatment by percutaneous stellate ganglion block: the STAR study’, by S. Savastano et al., https://doi.org/10.1093/eurheartj/ehae021.

Life-threatening ventricular arrhythmias (VAs) remain exceptionally challenging despite advances in management. Catheter ablation is very effective, as it has become safer and therefore more widely adopted.¹ However, several patients are not suitable for catheter ablation, or are very unstable and need to be stabilized before ablation, especially when they present with electrical storm (ES). Medical management [antiarrhythmic drugs (AADs)] in ES is often inadequate, with a delayed time to effect. Sedation, then intubation, are supportive measures. Neuraxial interventions such as stellate ganglion blockade (SGB)^2–5 or thoracic epidural anaesthesia⁶ show promise for the acute stabilization of patients.¹ The autonomic nervous system plays a critical role as the substrate for VA, at both the level of the heart and at each level of the neuraxis, and is, therefore, a highly attractive therapeutic target.⁷

In this issue of the European Heart Journal, Savastano and colleagues report the findings of a multicentre observational study designed to assess the efficacy of SGB in the management of ES.⁸ They enrolled a cohort of 131 patients from 19 Italian centres from July 2017 until June 2023. Some participants were enrolled retrospectively (in the coordinating centre in Pavia), and subsequent patients (other centres) were enrolled prospectively. Most enrolled patients had structural heart disease (mean left ventricular ejection fraction 25%) and 29% had acute myocardial infarction. Only patients with sustained VA (ventricular tachycardia or ventricular fibrillation) refractory to standard treatment (failed i.v. AAD or were intolerant) were eligible. In addition to AAD, treatment included mechanical circulatory support and general anaesthesia. The time at which SGB was implemented was not mandated in this study. The primary outcome of the study was defined as a 50% composite reduction of either antitachycardia pacing (ATP) or shocks (either from the patient’s internal defibrillator or externally) in the 12 h following SGB, in comparison with the preceding 12 h. Secondary outcomes were as follows: comparison of the cumulative total of events (ATP or shocks) in the 12 h preceding SGB in comparison with 12 h post-SGB; number of complications within 12 h of SGB; comparison of efficacy in patients who developed anisocoria (a measure of efficacy of SGB) vs. those without; comparison of the SGB approach; single vs. continuous infusion; and, finally, high vs. low volume centres.

To participate in this study and to implement SGB (this was an appealing aspect of this study), at least one member of each participating centre was required to undertake in-person formal study training. The outline, including theory and practical aspects, is included in the supplementary material of the paper. Operators included cardiologists, intensivists, and emergency physicians. Two approaches were permissible: an anatomic (anterior paratracheal, at the level of the left-sided Chassaignac’s tubercle, C6) or an ultrasound-guided approach (intrascalenic, with the injection of anaesthetic over the longus colli muscle, below the carotid artery). Local anaesthetic and dosage were not mandated in the study protocol. Operators could perform repeat injections for early recurrence within or after the expected duration of efficacy. They could also leave a catheter for continuous infusion—particularly in situations such as electrolyte disturbances, infection, or thyrotoxicosis (likely to take some time to reverse). Importantly, the procedure was carried out regardless of anticoagulation or antiplatelet status. The stellate ganglion side (right vs. left) was mandated in the protocol, with the first two attempts performed on the left and then on the right in the case of VA recurrences.

The principal finding of this study was that 92% (106/115) of the enrolled participants met the primary outcome (50% reduction of ATP or shocks for sustained VA 12 h post-SGB). An anatomic approach was carried out in 57.6% and an ultrasound-guided approach in 42.4%. A bolus and then continuous infusion was performed in 17.4%. Interestingly, most SGB procedures were performed prior to anaesthesia (80%) and most cases (86%) were performed on patients on antiplatelets (26.1%; 7.1% of whom were on dual antiplatelets); anticoagulants (31.5%; 18.5% of whom were either on oral vitamin K antagonists or direct oral anticoagulants, and 13% were on i.v. heparin); or both antiplatelets and anticoagulants (28.3%). Only 3 SGB procedures were right-sided.

The overall complications were very low. One patient suffered respiratory depression probably owing to toxicity from i.v. lidocaine administration, and was managed without complication. There were two minor complications (bradycardia and hypotension) and eight SGB-related, temporary adverse effects (4.2%). Temporary brachial plexus paralysis occurred in three patients, hoarseness in two, and vomiting, neck pain, and dysphonia in one patient each. It is unclear whether these were more likely to occur in those with continuous infusions. Although the majority (96, 73%) underwent a single SGB, 18% had two SGBs, and 9% underwent 3–5 SGBs to control ES. Neither centre volume nor assessment of efficacy (development of anisocoria) was significant. An acute effect was observed (per-procedure analysis) when 1 h pre- vs. post-SGB was compared. Although efficacy appeared higher with the anatomic approach, there were differences in the groups. The anatomic approach was generally performed in sicker patients, during cardiac arrest, with ventricular fibrillation (or a shorter ventricular tachycardia cycle length), or higher burden of VA. Time to VA after SGB was longer in those who received continuous infusions.

The authors are to be congratulated on the addition of the largest observational study to this emerging and exciting therapeutic option in a challenging group of patients. Indeed, the in-hospital mortality of this cohort was 27.5%, with most deaths occurring due to cardiogenic and septic shock, but some occurring due to ES itself. There are several strengths of this study. There is a clear reduction in VA burden (ATP and shocks) at 1 and 12 h post-SGB. Formal training, which included procedural aspects, was mandated. SGB was not associated with major complications, and most adverse effects were transient. This was particularly reassuring, given that most patients were anticoagulated or on antiplatelets. Importantly, the authors tested a stepwise approach which allowed several bolus SGBs (as well as continuous infusion) if VA was refractory.

There are also important limitations. Foremost, this study was observational, and therefore confounders such as other concomitant treatments or implantable cardioverter-defibrillator (ICD) programming changes are not accounted for. Second, there was no adjudication of the outcomes by study investigators. No data were presented up to hospital discharge (longer term follow-up data are also necessary). There was no separate collection of ATP and shock data, and also no protocol for anaesthetic dosages or SGB timing.

Several mechanisms explain why dampening sympathetic efferent activity is effective for VAs. Less is known about the pathophysiology of ES; however, the efficacy and duration of SGB may provide some clues. First, stimulation of either stellate ganglion alters ventricular excitability to promote arrhythmias.^9–11 Structural heart disease [myocardial infarction (MI) and heart failure (HF)] result in autonomic dysfunction—with a sympathetic shift through neurohormonal activation. This is associated with (and results from) autonomic remodelling (substrate) at the level of the intrinsic cardiac nervous system, extracardiac intrathoracic ganglia (stellate), and the central nervous system.⁷ The stellate ganglia of patients with cardiomyopathy and ES undergoing cardiac sympathetic denervation have demonstrated inflammation, neurochemical remodelling, oxidative stress, and satellite glial cell activation.¹² MI results in heterogeneity of sympathetic innervation and nerve sprouting in infarct border zones, which are vulnerable to VA.¹³ In both MI and HF, there is activation of an afferent, positive-loop cardiac sympathetic afferent reflex, increasing sympathetic tone.^7,14

It is important to note that from an anatomic viewpoint, the true stellate ganglia reside caudal to anaesthetic infiltration in SGB procedures, which generally target the transverse process of the sixth cervical vertebra. The stellate ganglion, specifically its superior half (inferior cervical ganglion), is commonly located anterior to the costotransverse joint of the first rib, just above or sometimes posterior to the apices of the lungs. This is in a highly vascular area, rendering direct access unsafe. Therefore, much of the effect of ‘SGB’ really is either dispersive, where the target is distant from the injection site (which may explain the need for additional boluses or anaesthetic infusions⁵), or due to direct effects on the cervical sympathetic trunk, including middle cervical ganglia, rather than the stellates themselves. The strategy of ‘testing’ the response of autonomic modulation by using a temporary means (SGB) could assist in determining responders from non-responders and therefore guide more invasive procedures, such as surgical sympathetic denervation.¹³ Finally, there is emerging single-centre, randomized data for targeting the sympathetic chain non-invasively using transcutaneous magnetic stimulation.¹⁵

Given the findings of this important study and, in the context of the current body of evidence, being supportive of SGB (despite the observational nature), it is quite reasonable to utilize SGB for ES when other approaches fail (Graphical Abstract). As most patients received SGB prior to general anaesthesia, one can advocate for its use prior to general anaesthesia. Current guideline¹⁶ recommendations give a class IIB indication for autonomic neuromodulation in patients with ES refractory to AAD and in whom catheter ablation is not feasible. However, there is no specific guidance as to the strategy, and particularly the role of SGB. The low risk profile of the procedure (in comparison with surgical sympathetic denervation and thoracic epidural anaesthesia) could influence future recommendations. In conclusion, SGB is a valuable therapeutic option in the management of ventricular arrhythmic storm.

Graphical Abstract.

SGB in the management of VA (electrical) storm: current evidence, proposed mechanism of action and contemporary management. SGB, stellate ganglion block; VA, ventricular arrhythmia; ES, electrical storm; STAR, stellate ganglion block for arrhythmic storm; IQR, interquartile range; SG, stellate ganglion; SHD, structural heart disease; MI, myocardial infarction; HF, heart failure; CNS, central nervous system; fMRI, functional magnetic resonance imaging; ICD, internal cardioverter defibrillator; AAD, antiarrhythmic drugs; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; LVAD, left ventricular assist device.

Declarations

Disclosure of Interest

K.S. has developed IP relating to cardiac neural control (assigned to UCLA) and is a co-founder of NeuCures Inc. There are no other disclosures to declare.

Funding

K.S. is supported by NHLBI P01, HL164311.