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.

Keywords: cardiac autonomic nervous system; cardiac sympathetic denervation; catecholaminergic polymorphic ventricular tachycardia; long QT syndrome; sudden cardiac death.

Figure 1

Cardiac nervous system organization in humans. Blue: afferent nervous system with its ganglia: nodose ganglia and C7-T4 dorsal root ganglia (DRG). Green: parasympathetic efferent nervous system. Red: sympathetic efferent nervous system. All the afferent and efferent structures outside the central nervous systems are bilateral, although mostly represented as unilateral for simplicity. Cardiac afferent fibers traveling across the paravertebral sympathetic ganglia (usually referred to as cardiac sympathetic afferent fibers) directly reach the DRG without having synapsis before. These fibers mediate cardio-cardiac sympathoexcitatory spinal reflexes that significantly increase the sympathetic output to the heart. Left cardiac sympathetic denervation (LCSD) consists in the removal of the left thoracic sympathetic chain and paravertebral ganglia from T1 to T4. Since ipsilateral DRG are spared by LCSD, a left afferent reinnervation from the DRG to the heart is theoretically possible with time. On the other hand, the left efferent sympathetic system from T1 to T4 is interrupted at a preganglionic level; therefore, no ipsilateral efferent sympathetic reinnervation is possible after LCSD.

Figure 2

Percentages of recurrences after left cardiac sympathetic denervation (LCSD) in 38 CPVT patients who had previously suffered major cardiac events despite optimal medical therapy. The majority received a complete LCSD (n = 33), the remaining (n = 5) an incomplete LCSD. Modified from De Ferrari et al. (129) with permission.