ABC | Volume 112, Nº6, June 2019

Editorial Scanavacca and Hachul Vagal denervation in patients with vasovagal syncope Arq Bras Cardiol. 2019; 112(6):709-712 of 9.2 months, no patient showed syncope recurrence, or complications. In 2011, the authors reported the late outcome of 43 patients with recurrent NMS, submitted to ablation. Forty patients remained asymptomatic during a mean follow-up of 45.1 ± 22 months and no significant complications were observed. 5 More recently, Yan et al. 14 performed vagal denervation in ten consecutive patients with a mean age of 50.4 ± 6.4 years and recurrent episodes of NMS, in which traditional therapies were not effective. The authors used the high‑frequency stimulation (HFS) technique, described by the Oklahoma group, in order to locate GP based on induced vagal response. 30 The endpoint of the procedure was the inhibition of the vagal response at the target sites. During a mean follow‑up of 30 ± 16 months, no patient had syncope episodes, but 5 patients reported transient symptoms. There were no complications. 14 Sun et al. 15 reported the long-term outcome of 57 consecutive patients (aged 43.2 ± 13.4 years; 35 women) with refractory vasovagal syncope, who underwent left atrium GP ablation. The GP were located based on the combination of anatomic features obtained by the electroanatomic mapping and positive response (vagal hyperactivity) during HFS, on expected GP locations. During a mean follow-up of 36± 22 m, 52 (91.2%) patients had no syncope. However, 16 patients showed prodromal symptoms. Autonomic evaluation revealed reduced vagal activity, persistent for at least 12 months after the procedure. The only side effect was sinus tachycardia observed in one patient. 15 Zhao et al. 16 performed catheter ablation in 11 patients (8 men, with mean age of 45 ± 10 years) with a long history of symptomatic bradycardia. All anatomic locations of the GP were confirmed by HF stimulation before ablation. The procedure endpoint was the elimination of vagal response at the ablation sites. During a mean follow-up of 18 ± 6 months, all patients reported significant symptom improvement. There was a significantly increase in the mean sinus heart rate, which persisted for 12 months. 16 The main limitations of these studies are the absence of control groups and randomization. The already known placebo effect of interventions in patients with NMS does not allow considering their good results as definitive to regularly apply the GP ablation in clinical practice. Despite such limitations many other authors have reported selected cases in which patients had advanced atrioventricular block induced by excessive vagal activity and had indication for pacemaker impantation. 6-13 Although the GP mapping and ablation technique were not identical, no patient had complications and pacemaker implantation was avoided. Some authors delivered RF pulses guided by a positive vagal action induced by HFS. Others delivered RF pulses based on the characteristics of the electrograms, or at the anatomic sites where the presence of GP clusters was highly probable, based on previous anatomical reports. 17-20 We investigated the effectiveness of vagal ablation in 14 patients (7 men, mean age of 34 ± 13 years) with symptomatic cardioinhibitory syncope, severe sinus bradycardia or advanced AV block, no structural heart disease, and pacemaker indication. The GP were identified and ablated based on the anatomy obtained by the electroanatomical mapping analysis. During a mean follow-up period of 22 ± 11 months, 10 patients (71.4%) showed significant clinical and ECG improvement: no syncope recurrence or symptomatic bradycardia were observed at daytime Holter monitoring during the follow-up. However, transient second‑degree atrioventricular block was still detected, exclusively at night. The remaining four patients (28.6%), despite showing acute vagal activity attenuation, had syncope recurrence or symptomatic bradycardia and underwent pacemaker implantation. No significant complications were observed during or after the procedure. 18 Therefore, until now, no consensus has been achieved about the ideal electrophysiological technique to perform vagal activity attenuation: if through extensive ablation areas based on fragmented electrograms, or by anatomical landmarks; if ablating all right and left atrial GP areas, or those that directly innerve the sinus and AV nodes, in both sides of the septum; or only the right side of the septum, or even spots in the superior vena cava. 9,10,20 Another important controversial point is how to establish the procedure endpoint, whether reaching an expected heart rate elevation such as 20% of basal cardiac frequency, shortening the P-P interval > 120 ms; eliminating prior vagal response induced by HFS on the target GP or absence of an additional heart rate elevation after GP ablation with the atropine test. Recently, an extracardiac vagal stimulation with high frequency pulses, performed directly on the right or left cervical vagal trunk through retrograde jugular vein catheterization was suggested to evaluate vagal response before, during and at the end of the procedure. This method has been proposed to obtain an objective, faster and reproducible evaluation of the ablation effect during the procedure. 31 Finally, it is important to define a reproducible autonomic evaluation in patients considered for vagal denervation. The most frequent analysis prior to the procedure has been the analysis of time-domain and frequency-domain heart rate variability (HRV), during 24h Holter monitoring. Small segments of the ECG are also evaluated during the tilt table test, in the last 5 minutes of supine position and the first 5 minutes of orthostatic exposure. It is also important to identify patients with the vasodepressor component, in which prodromal symptoms will probably persist, even after effective sinus and/or AV node denervation. The atropine test (0.04 mg/Kg), complemented with exercise stress test, have been performed to evaluate the vagal reserve and to rule out a possible sinus node dysfunction. Such autonomic evaluation should be repeated during the follow-up aiming to identify the long-term outcome of the autonomic modulation. In summary, the experimental and clinical background suggest that RF ablation of GP may promote significant vagal withdrawal in the sinus and AV nodes, in patients with very symptomatic neurally mediated bradycardia syndromes. However, its effectiveness, safety and reproducibility need a more thorough evaluation. Different techniques have been proposed to successfully identify and ablate the sites of vagal inputs to the atria. Therefore, a randomized multicenter study is fundamental not just to establish the effectiveness of vagal denervation and the long-term clinical impact on symptoms and safety to the patient but also to identify the best techniques to obtain vagal response attenuation, with smaller areas of ablation. 710