Hyperactivity of the parasympathetic part of the autonomic nervous system may lead to cardioinhibitory vasovagal syncope (VVS), functional bradycardia, or atrioventricular block (AVB). Elimination or reduction of the enhanced vagal tone may be an effective therapeutic approach.1-8
Cardioneuroablation (CNA), performed by means of radiofrequency (RF) catheter ablation of ganglionated plexi (GP) in the left (LA) and right atrium (RA) is a promising new method for the treatment of vagally mediated VVS or functional bradycardia / AVB. The procedure was first described and used in clinical practice by Pachon and colleagues in 2005.9 Since then, data confirming the effectiveness of CNA is still growing.1-8 However, several issues such as selection of patients, CNA protocol, and procedural endpoints have not yet been clearly established.1-8 Herein we present a patient with cardioinhibitory VVS treated successfully with CNA.
A 33-year-old female was urgently transferred to our center for CNA because of prolonged asystole triggered by a biopsy procedure. The asystole lasted about 30 seconds until the resuscitation was started and required temporary cardiac pacing. She was continuously monitored following this event, and spontaneous 1-minute asystole was recorded a few days later. She had a 12-year history of VVS. Coronary angiography and echocardiography were normal.
In our center, the first step in qualifying for CNA is the atropine test. An increase in heart rate (HR) >25% is regarded as satisfactory response, suggesting that parasympathetic activation may significantly contribute to reflex bradycardia or asystole. In this patient, her HR after atropine injection increased 47% from 69 to 102 beats per minute. In addition, during tilt testing, cardioinhibitory syncope with asystole of 13 seconds was reproduced.
The procedure was performed under general anesthesia, because extracardiac vagal stimulation (ECVS) may cause spasm in the muscles of the neck and be painful for the patient. A decapolar steerable catheter was placed into the coronary sinus (CS) and another decapolar catheter was placed in the right and subsequently in the left jugular vein to perform ECVS. An intracardiac echocardiography (ICE) probe was placed in the RA. Electroanatomical 3D maps of the RA and LA were created using the CARTO 3 system (Biosense Webster, Inc., a Johnson & Johnson company) and the NAVISTAR THERMOCOOL SMARTTOUCH catheter (Biosense Webster). Transseptal puncture (TP) was performed under ICE guidance. After TP, activated clotting time (ACT) was controlled every 20-30 minutes and maintained >350 seconds. Surface ECG and intracardiac ECG were recorded using an EP recording system. Before and after the procedure, sinus node recovery time (SNRT), corrected SNRT (cSNRT), AV block cycle length (AVBCL), and effective refractory period (ERP) of the AV node (AVN) were measured. The ECVS was performed using a neurostimulator that was constructed by Dr. Pachon (Sao Paulo, Brazil). Blood pressure and oxygen saturation were noninvasively monitored.
Ablation strategy was based on presumed anatomical localization of the GP combined with identification of sites with fragmented bipolar electrograms as described by Aksu et al.10 Ablation was started in the LA at the anterior antrum of the right superior pulmonary vein where the right anterior GP (RAGP) is usually located. Next, RF applications were delivered at the infero-posterior part of the interatrial septum where the right inferior GP (RIGP) is usually localized. Finally, RF ablation in the RA was performed at the junction between the RA and superior vena cava (SVC) as well as the CS ostium, close to the sites of ablation at the area of RIGP when targeted from LA. The RF energy was delivered in the power control mode (30-35 W) with an irrigation flow of 17-30 ml/min and temperature limit max 43°C. The applications were continued until the Ablation Index (AI) reached a value of 400 (RIGP and RA/SVC junction) and 450 (RAGP from LA) (Figure 1). AI is a marker of lesion quality that incorporates contact force, time, and power in a weighted formula, and has been shown to accurately estimate lesion depth; thus, AI provides good quality of each RF application during ablation.
Before RF ablation, ECVS from both the right and left jugular veins was performed and confirmed a strong vagal response including sinus arrest and AVB during pacing from the CS (Figure 2). The ECVS was performed under fluoroscopy and vascular ultrasound guidance (Figures 3 and 4). After RFCA, ECVS showed no vagal response, which confirmed parasympathetic denervation (Figure 2). Electrophysiological parameters improved, including HR, SNRT, cSNRT, and AVBCL (Figure 5). After that, 2 mg of atropine was given and no increase in heart rate was noted. The patient had no recurrence of syncope during 8-month follow-up.
This case shows that prolonged asystole due to enhanced vagal tone may lead to severe morbidity. CNA is a new and promising technique for the treatment of cardioinhibitory VVS, functional bradycardia, and atrioventricular block. Due to a lack of randomized, prospective trials, CNA has no class of recommendation in the current 2017 ACC/AHA/HRS and 2018 ESC guidelines for the diagnosis and management of syncope.11,12 However, data in literature is still growing, and a prospective, randomized study is ongoing (NCT03903744, sponsored by the Centre of Postgraduate Medical Education in Warsaw, Poland). Currently, the most widely used indications for CNA include cardioinhibitory VVS, mixed VVS (cardioinhibitory and vasodepressor), symptomatic bradycardia, and AVB due to hyperactivity of the parasympathetic part of the autonomic nervous system. In addition, a response to atropine is a prerequisite before considering CNA.
The technique is still evolving. To date, there is no consensus on which endpoints are optimal. Pachon et al13 defined endpoints of CNA as lack of vagal response during ECVS and lack of response to atropine after the procedure. Aksu et al showed that elimination of fragmented electrograms, improved electrophysiological parameters, and complete elimination of AVB were suitable endpoints of CNA.10 Elimination of all vagal responses during endocardial high-frequency stimulation at each identified target was assumed as an endpoint by Yao et al.3,5 In our center, an anatomical approach with fragmented electrograms elimination and ECVS performed under both fluoroscopic and vascular ultrasound guidance are routinely used.
In summary, CNA is a promising technique, especially in young patients with symptomatic bradycardia, in whom it is preferred to avoid if possible. Clinical indications, optimal protocol, efficacy, and safety still require definition and validation.
Disclosures: The authors have no conflicts of interest to report regarding the content herein.
- Pachon JC, Pachon EI, Cunha Pachon MZ, et al. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace. 2011;13:1231-1242.
- Yao Y, Shi R, Wong T, et al. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol. 2012;5:279-286.
- Sun W, Zheng L, Qiao Y, et al. Catheter ablation as a treatment for vasovagal syncope: long-term outcome of endocardial autonomic modification of the left atrium. J Am Heart Assoc. 2016;5(7):e003471.
- Aksu T, Golcuk E, Yalin K, et al. Simplified cardioneuroablation in the treatment of reflex syncope, functional AV block, and sinus node dysfunction. Pacing Clin Electrophysiol. 2016;39:42-53.
- Hu F, Zheng L, Liang E, et al. Right anterior ganglionated plexus: the primary target of cardioneuroablation? Heart Rhythm. 2019;16(10):1545-1551.
- Piotrowski R, Baran J, Kułakowski P. Cardioneuroablation using an anatomical approach: a new and promising method for the treatment of cardioinhibitory neurocardiogenic syncope. Kardiol Pol. 2018;76:1736-1738.
- Calo L, Rebecchi M, Sette A, et al. Catheter ablation of right atrial ganglionated plexi to treat cardioinhibitory neurocardiogenic syncope: a long-term follow-up prospective study. J Interv Card Electrophysiol. 2020 Aug 6. doi:10.1007/s10840-020-00840-9
- Aksu T, Padmanabhan D, Shenthar J, et al. The benefit of cardioneuroablation to reduce syncope recurrence in vasovagal syncope patients: a case-control study. J Interv Card Electrophysiol. 2021 Feb 1. doi:10.1007/s10840-020-00938-0
- Pachon JC, Pachon EI, Pachon JC, et al. Cardioneuroablation-new treatment for neuro-cardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace. 2005;7:1-13.
- Aksu T, Guler TE, Bozyel S, Yalin K. Selective vagal innervation principles of ganglionated plexi: step-by-step cardioneuroablation in a patient with vasovagal syncope. J Interv Card Electrophysiol. 2020 May 11. doi:10.1007/s10840-020-00757-3
- Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2017;70:e39-e110.
- 12. Brignole M, Moya A, de Lange FJ, et al; ESC Scientific Document Group. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018;39:1883-1948.
- 13. Pachon-M EI, Pachon-Mateos JC, Higuti C, et al. Relation of fractionated atrial potentials with the vagal innervation evaluated by extracardiac vagal stimulation during cardioneuroablation. Circ Arrhythm Electrophysiol. 2020;13:e007900.