ABC | Volume 112, Nº6, June 2019

Editorial Ganglionated Plexi Ablation to Treat Patients with Refractory Neurally Mediated Syncope and Severe Vagal-Induced Bradycardia Mauricio Scanavacc a a nd Denise Hachu l Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil Mailing Address: Mauricio Ibrahim Scanavacca • Av. Joaquim C. A. Marques, 1205. Postal Code 05688-021, Morumbi, SP – Brazil E-mail: mibrahim@cardiol.br , mauricio.scanavacca@gmail.com Keywords Ganglia, Autonomic; Catheter Ablation; Syncope,Vasovagal; Bradycardia; Autonomic Nervous System. DOI: 10.5935/abc.20190107 Neurally mediated syndrome (NMS) is the most common cause of and transient loss of consciousness and usually causes anxiety and concerns for patients and their families. Clinical investigation and explanations about benignity, in association to lifestyle modifications and teaching methods to abort the vagal reflex are the initial and effective approaches to manage the majority of patients. 1-3 However, in some cases, the loss of consciousness occurs suddenly, without prodromal symptoms and the patient does not have the opportunity to prevent falls, which may lead to severe physical trauma. Specific medications have been proposed trying to control the symptoms and pacemaker implantation has been recommended in the refractory cases of cardioinhibitory reflexes. 1-3 In 2005, Pachón et al. 4 proposed using a catheter ablation technique to attenuate vagal activity on the sinus and AV nodes, through radiofrequency (RF) ablation of the sites related to vagal inputs to the atria. This procedure aimed to promote better quality of live for patients with refractory NMS and severe bradycardia, avoiding pacemaker implantation, especially in young individuals. 4 Since that time, many reports have confirmed that atrial vagal modulation by catheter ablation is feasible in clinical settings, for patients with vagal induced marked and symptomatic bradycardia. 5-20 However, those studies came from relatively few centers, such as case reports, 5-13 or fromnon-randomized series involving a limited number of patients. 14-20 Additionally, until now, there is no consensus about the criteria for patient selection, about how to perform an autonomic evaluation prior and post ablation, the best technique to be applied, the endpoints to conclude the procedure and what to expect during the outcome. These are the main reasons why vagal attenuation by catheter ablation has not been considered a possible treatment in the international guidelines of NMS management. 1-3 Almost 50 years ago, experimental studies demonstrated that the sinus and atrioventricular nodes receive specific autonomic innervation, which can be surgically destroyed. 21 However, current techniques to promote vagal denervation have been based on a more recent descriptions of atria innervation. 22,23 It has been demonstrated that cardiac parasympathetic neurons get together with postganglionic sympathetic fibers and fat tissue (fat pads), in specific areas of the epicardium, adjacent to the posterior walls of left and right atria. Such ganglionated plexi (GP), working together, coordinate a sophisticated network that regulates cardiac functions, and more precisely the cardiac rhythm. 24 The Oklahoma group has worked intensively to understand GP functional activities and has observed, in experimental studies, that despite the intense interconnections among GP, the sinus node is mainly innervated by the plexi, anatomically situated in the superior portion of the posterior interatrial septum, between the superior vena cava and anterior to the right superior PV. The AV node is manly innervated by the right inferior plexi, located behind the coronary sinus ostium and between the inferior vena cava and right inferior PV. The sinus node and AV node still receive fiber connections from the left superior and left inferior GP located nearby the left pulmonary veins. However, these interconnections necessary cross the right superior and right inferior PV GP to reach the sinus and AV nodes. 24 Additionally, extra GPs connections might influence the sinus and AV node innervation. 22-24 It has also been suggested that the intrinsic autonomic nervous system of the heart receives inputs from mechanical and chemosensory receptors located in both ventricles. 25 Those autonomic nervous interconnections could have an important role in the pathophysiology of NMS and might explain some behaviors observed in patients submitted to GPs ablation, who showed additional improvement in the peripheral vasovagal reflex. Sinus node vagal denervation was a fortuitous observation detected by the occurrence of an augmented vagal response triggered during catheter ablation of atrial fibrillation and also, the subsequent increase in heart rate observed soon after the procedure. Those findings were more evident when extensive ablation of the PV antrum, where GPs are frequently located, was performed. 26,27 Autonomic tests performed after PV isolation confirmed an effect of the vagal denervation of the sinus node in many patients; however, a controversy still persists regarding the effect of persistent atrial vagal denervation on the long term outcome. 28,29 Those serendipity findings opened a new possibility for the treatment of the negative effects of excessive vagal activity in some patients. Different techniques have been used for sinus and AV node vagal denervation: one is based on the hypothesis that autonomic innervation can be recognized by the characteristics of the endocardial fractionated electrograms (AF Nests), and detected by Fast-Fourier transform analysis. 4 The original report from Pachón et al. 5 in 2005, described twenty-one patients with a mean age of 48 years, six with neurally mediated reflex syncope, and 15 with sinus node dysfunction or functional high-degree atrioventricular block, who underwent vagal denervation. In a mean follow-up 709