Cardiac sympathetic denervation for treatment of ventricular arrhythmia: Where are we now?

Chance M Witt and Christopher J McLeod (Rochester, USA) review current treatment of ventricular arrhythmias with cardiac sympathetic denervation. 

What is cardiac sympathetic denervation?

Most electrophysiologists are fully aware of the complex interplay between the autonomic nervous system and cardiac arrhythmias. There is no doubt that sympathetic effects, parasympathetic effects, and their combination contribute to the initiation and maintenance of both atrial and ventricular arrhythmia. The question is: how can we manipulate the autonomic nervous system to negate these pro-arrhythmic effects?

There are various treatments in use to target the autonomic nervous system including beta-blockers, which limit the effects of the end product of the sympathetic nerves, and ganglionated plexus ablation, which attempts to eliminate the influence of the intrinsic cardiac autonomic nervous system to treat atrial fibrillation. Cardiac sympathetic denervation generally refers to interrupting the sympathetic input to the heart by removing or blocking the extrinsic sympathetic nerves (outside the pericardium), typically in or around the stellate ganglion. The stellate ganglion level is chosen because it seems to create an adequate sympathetic block to the heart and denervation above this level can cause side effects, such as Horner’s syndrome. Cardiac sympathetic denervation is now commonly accomplished by a video-assisted thoracoscopic surgical procedure which bisects the stellate ganglion removing the lower half along with a few ganglia below it. Cardiac sympathetic denervation can also more broadly refer to procedures which attempt to block the effect of the sympathetic nerves by a percutaneous injection of a local anaesthetic and thus temporarily denervate the heart.

What do we know?

Cardiac sympathetic denervation has primarily been used as a treatment for various causes of ventricular tachycardia (VT). Based on multiple studies, including hundreds of patients, over many years, cardiac sympathetic denervation is an effective treatment for preventing VT in certain patients with long QT syndrome.^1–3 This is such a powerful treatment that some experts have even advocated that not offering it as a therapy for these patients is suboptimal medical care.⁴ The positive effect of cardiac sympathetic denervation extends to another genetic condition, catecholaminergic polymorphic VT.⁵ With the obvious autonomic involvement, it is intuitive that cardiac sympathetic denervation would be a beneficial treatment in these patients.

The benefit for VT caused by various other underlying diseases is less certain. One large study demonstrated that prophylactic cardiac sympathetic denervation in patients with recent myocardial infarction has a similar beneficial effect to beta-blockers at preventing VT.⁶ Furthermore, many case reports and small series suggest that some patients with recurrent VT and VT storm may be successfully treated by cardiac sympathetic denervation in the form of surgery and stellate ganglion block with anaesthetic injection.^7,8

Where do we need more information?

In general, however, the role of cardiac sympathetic denervation for preventing recurrent VT in acquired, ischaemic and non-ischaemic cardiomyopathy is not entirely clear. From studies, as well as our unpublished data and anecdotal experience, there are many patients who do not respond, although many who do. A planned randomised study, called PREVENT VT (NCT01013714), should help bring clarity to this issue. In this study, cardiac sympathetic denervation surgery will be performed on both the left and right side, which is supported by some recent evidence, although there have been questions in the past about the effects of right sided denervation.⁹

The efficacy of cardiac sympathetic denervation for patients in the throes of a VT storm is even less clear, with cohort studies including relatively few patients and the urgency of the clinical situation preventing a stepwise or randomised approach. Anecdotally, stellate ganglion block with an injected anaesthetic as the method of cardiac sympathetic denervation is expeditious and potentially effective in this group. Yet, whether stellate ganglion block is the same as surgical denervation is not clear. Even when the anaesthetic is injected in exactly the correct location the effects may be different, and despite imaging guidance, precision pinpointing of the relevant innervation is not reliable. As a corollary, there is currently no robust marker that the heart has been denervated. However, an emerging technique involving measurement of stellate/sympathetic nerve activity via surface electrocardiogram (ECG) is a promising and exciting possibility.¹⁰

In summary, cardiac sympathetic denervation is markedly effective for long QT syndrome and catecholaminergic polymorphic VT. For the remaining ventricular arrhythmia syndromes, early data are encouraging in certain subgroups, but more information is needed. Upcoming clinical trials should provide some answers; however, the role of stellate ganglion block with injected anaesthetics and the use of non-invasive methods for proving cardiac denervation are important topics for further study.

References

1. Schwartz PJ, Locati EH, Moss AJ, Crampton RS, Trazzi R, Ruberti U. Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome. A worldwide report. Circulation 1991;84:503–11
2. Schwartz PJ, Priori SG, Cerrone M et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation 2004;109:1826–33
3. Collura CA, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. HeartRhythm 2009;6:752–9
4. Schwartz PJ. Efficacy of left cardiac sympathetic denervation has an unforeseen side effect: medicolegal complications. HeartRhythm 2010;7:1330–2
5. De Ferrari GM, Dusi V, Spazzolini C et al. Clinical management of catecholaminergic polymorphic ventricular tachycardia: The role of left cardiac sympathetic denervation. Circulation 2015;131:2185–93
6. Schwartz PJ, Motolese M, Pollavini G et al. Prevention of sudden cardiac death after a first myocardial infarction by pharmacologic or surgical antiadrenergic interventions. Journal of Cardiovascular Electrophysiology 1992;3:2–16
7. Vaseghi M, Gima J, Kanaan C et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: Intermediate and long-term follow-up. HeartRhythm 2014;11:360–6
8. Nademanee K, Taylor R, Bailey WE, Rieders DE, Kosar EM. Treating electrical storm: Sympathetic blockade versus advanced cardiac life support-guided therapy. Circulation 2000;102:742–7
9. Ajijola OA, Vaseghi M, Mahajan A, Shivkumar K. Bilateral cardiac sympathetic denervation: why, who and when? Exper Rev Cardiovasc Ther 2012;10:947–9
10. Doytchinova A, Hassel JL, Yuan Y et al. Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram. HeartRhythm 2017;14(1):25–33

Chance M Witt and Christopher J McLeod are with the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, USA