CardioneuROablation: coMparison of Right Versus Left Atrial Approach in Patients With Reflex syNcope. The Roman 2 Randomized Controlled Prospective Study

Introduction. Reflex vaso-vagal syncope (VVS) is the most frequent cause of transient loss of consciousness in general population. It markedly decreases quality of life and may lead to injury. The mechanisms of VVS are complex with enhanced parasympathetic activity being one of the most important, leading to prolonged asystole and/or vasodilatation and syncope.

Treatment of VVS remains a challenge. Non-pharmacological treatment such as fluid and salt intake, avoiding situations triggering syncope or tilt training is not effective in a significant proportion of subjects with syncope. Pharmacotherapy is even less effective. Syncope recurs in 50% of patients. Alternative therapy, especially in patients with prolonged asystole, is pacemaker implantation, recommended by the guidelines in patients aged > 40 years with documented spontaneous cardioinhibitory VVS and severe symptoms. However, permanent pacing occurs ineffective in at least 12-25% of patients. In addition, VVS occurs predominantly in young persons in whom permanent pacing should be avoided as much as possible. Thus, there is a need for new treatment options in VVS.

Cardioneuroablation (CNA) is a relatively new method, introduced by Pachon et al in 2005. To date, numerous small and medium volume reports have been published, showing CNA efficacy between 40% and 100%, at a mean level of around 85-90% at one-year follow-up. The procedure consists of radio-frequency (RF) ablation of ganglionated plexi (GP) located in the epicardial fat around right (RA) and left atrium (LA). The RF-induced injury of GP markedly diminishes vagal tone because, contrary to the adrenergic nerve endings, parasympathetic fibers predominate in GP and do not regenerate, therefore, procedural effects are probably durable.

The optimal technique for performing CNA has not been established and operators use various approaches. There are at least three issues to be addressed. The first one is the choice of cardiac chamber for CNA. Some operators perform RF ablation in the RA only whereas others in both atria or mainly in the LA.

Secondly, the procedural end-points are also inconsistent. Some use simple measures such as increase in heart rate (HR) and changes in other electrophysiological parameters suggesting vagal withdrawal whereas others use extra cardiac vagal stimulation (ECVS) performed from the right (RIJV) and left internal jugular veins (LIJV) to demonstrate sinus arrest and atrio-ventricular (AVB) block at baseline and lack of ECVS effects after successful total vagal denervation. The ECVS was introduced by Pachon and seems to be an excellent intra-procedural end-point, however, it is not clear whereas it's use is required to obtain favorable long-term results. Moreover, it is not known whether total vagal denervation (no sinus arrest and no AVB) is mandatory or maybe partial denervation (no sinus arrest or AVB) is sufficient to prevent syncope recurrences.