Cardiac Sympathetic Denervation in Channelopathies

Abstract

Left cardiac sympathetic denervation (LCSD) is a surgical antiadrenergic intervention with a strong antiarrhythmic effect, supported by preclinical as well as clinical data. The mechanism of action of LCSD in structurally normal hearts with increased arrhythmic susceptibility (such as those of patients with channelopathies) is not limited to the antagonism of acute catecholamines release in the heart. LCSD also conveys a strong anti-fibrillatory action that was first demonstrated over 40 years ago and provides the rationale for its use in almost any cardiac condition at increased risk of ventricular fibrillation. The molecular mechanisms involved in the final antiarrhythmic effect of LCSD turned out to be much broader than anticipated. Beside the vagotonic effect at different levels of the neuraxis, other new mechanisms have been recently proposed, such as the antagonism of neuronal remodeling, the antagonism of neuropeptide Y effects, and the correction of neuronal nitric oxide synthase (nNOS) imbalance. The beneficial effects of LCSD have never been associated with a detectable deterioration of cardiac performance. Finally, patients express a high degree of satisfaction with the procedure. In this review, we focus on the rationale, results and our personal approach to LCSD in patients with channelopathies such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.

Acute hemodynamics of cardiac sympathetic denervation

“…These acute hemodynamic effects of bilateral CSD have been documented in few isolated case reports [ 16 ], but no substantial study has yet looked specifically for this effect in the intra-operative and immediate post-operative periods. This particular hemodynamic effect, though of smaller magnitude, has been observed in earlier studies where thoracic sympathectomy was performed for palmar hyperhidrosis and facial blushing [ [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] ]. This might have been mainly due to the fact that the stellate ganglion was not resected in these cases.…”

“…The stellate ganglia convey a large amount of cardiac sympathetic postganglionic fibres. The remaining are provided by T2-4 paravertebral ganglia [ 26 ].These ganglia receive inputs from multiple spinal levels, process those and finally deliver output to the heart via the post-ganglionic neurons. Nor-epinephrine is the final neurotransmitter of these post-ganglionic neurons.…”

A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2

“…Although a marked reduction in the incidence of aborted cardiac arrest and syncope is usually seen after LCSD, 20% to 50% of patients with high-risk LQTS have experienced at least 1 recurrent arrhythmic event after LCSD [23,24]. Therefore, LCSD is an important therapeutic option for the management of patients with a first episode of syncope that occurs despite beta-blocker therapy, but it should not be considered as a curative or alternative to ICD in patients with high risk of sudden cardiac death [25].…”

Brain-Heart Afferent-Efferent Traffic

“…Through a mechanistic understanding of the adverse remodeling of the nervous system coupled to the myocyte substrate, focused neuromodulation therapies can be designed to mitigate disease progression and improve the morbidity/mortality outcome for patients. Such approaches may include such things as surgical removal of the T1-T4 levels of the paravertebral chain to treat intractable ventricular tachycardia [211][212][213], to bioelectric interventions targeted to the afferents of the carotid sinus [214,215] and vagal nerve stimulation for treatment of atrial fibrillation [216,217] and heart failure [218,219].…”