Acute electRophysiOlogical Changes of Ventricular Myocardium Following cArdioneuroablatioN for Asystolic Reflex Syncope

Cardiac arrhythmias, both atrial and ventricular, can be modulated by changes in autonomic tone. In ventricular arrhythmias, sympathetic tone is thought to be pro-arrhythmic whereas increased parasympathetic tone exerts protective effects. The main mechanisms responsible for parasympathetic protection involve direct effects on ventricular repolarisation, maintaining electrical stability via preservation of gap junction communication between myocytes, reducing heterogeneity of action potential duration, and decreasing circulating catecholamines and inflammatory markers. It has also been shown that enhanced parasympathetic activity increases ventricular fibrillation (VF) threshold. Also, termination of ventricular tachycardia (VT) by manoeuvres leading to augmentation of parasympathetic tone has been demonstrated. Numerous experimental studies showed that vagal nerve stimulation may decrease susceptibility to ventricular arrhythmias.

Cardioneuroablation (CNA) is a new promising method to treat reflex syncope which is due to vagally-induced functional sinus arrest or atrio-ventricular block (AVB). The goal of the procedure is to ablate post-ganglionic endings of parasympathetic part of autonomic nervous system (ANS), located in ganglionated plexi (GP) in the epicardial fat and in the myocardium. Although both sympathetic and parasympathetic nerves are localised in GPs, the latter ones only barely regenerate. Therefore, CNA-induced damage of the parasympathetic part of GP is greater and more durable than that of the sympathetic part of ANS. Because increased vagal activity is one of the main mechanisms leading to reflex sinus arrest or atrio-ventricular (AV) block, targeting this part of ANS by CNA may prevent recurrences of reflex syncope. Indeed, it has been shown that CNA may be effective in approximately 80-90% of very symptomatic subjects with reflex syncope.

While the reduction of parasympathetic drive to the atrial GPs, responsible for sinus node and AV conduction, seems to be logical and effective way for treating hypervagotonic reflex syncope, CNA-induced changes at the ventricular level may be theoretically harmful. As mentioned above, parasympathetic tone exerts protective effects on ventricular arrhythmias. Recently, the long-term safety of CNA has become an issue raised by some investigators. They expressed concerns that CNA-induced chronic and long-lasting decrease in parasympathetic activity may be dangerous during the future life of usually young people undergoing CNA nowadays. For instance, if they develop coronary artery disease, heart failure or other cardiac diseases which increase propensity of ventricular arrhythmias, lack of parasympathetic protection may lead to the occurrence of complex or even life-threatening ventricular arrhythmias.

Data in literature on possible proarrhythmic effects of CNA are limited and not uniform. From the anatomical and physiological point it has been shown many years ago that destruction of cardiac innervation at the atrial level may also damage ventricular innervation downstream. Although CNA targets GP localised mainly around the left and right atria, responsible for sinus and AV nodes innervation, ventricular GPs may be also affected indirectly by alterations in interaction with atrial GPs or even by direct ablation of some of ventricular GPs. According to Pauza et al. there are several ventricular GPs which are located in the epicardial fat surrounding the aortic root, close to right and left coronary artery ostia, at the area of the proximal posterior descending coronary artery, close the proximal right acute marginal coronary artery, and at the origin of the left obtuse marginal coronary artery. However, the number of ventricular GPs is much lower than that of the atrial ones (20% of atrial GPs) and their density is also lower. Thus, it is very likely that during ablation of some "atrial" GPs like postero-medial left GP (PMLGP) or within the coronary sinus (CS) also ventricular GPs integrity and function may be altered.

Specific data in literature on possible pro-arrhythmic effects of CNA on ventricular myocardium are scarce. A few experimental studies suggested that decreasing the parasympathetic drive to the heart by ablating epicardial GP's increases susceptibility to ventricular arrhythmias both in normal and ischaemic animal hearts. Also one recent study showed that acute ischaemia occurring 6 weeks after CNA was associated with significantly higher incidence of VF than in control untreated swine. As far as human data is concerned, a few cases of possible proarrhythmia - polymorphic VT induction after pulmonary vein isolation with concomitant parasympathetic denervation or after pure CNA, have been described.