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Electroanatomic-mapping-guided cardioneuroablation versus combined approach for vasovagal syncope: a cross-sectional observational study



This study was designed to assess the efficacy of electroanatomic-mapping (EAM)-guided cardioneuroablation (CNA) vs combined approach for vasovagal syncope (VVS).


Twenty patients with VVS refractory to conventional treatments who underwent CNA in our institution were enrolled in the study. Twelve of these patients underwent recently introduced EAM-guided CNA using signal-based approach while 8 patients underwent combined CNA using a combination of high-frequency stimulation and spectral analysis. Both atria and coronary sinus were divided into seven segments to categorize distribution of ganglionated plexi in ablation sites. Clinical responses were evaluated and compared in terms of prodromal symptoms and syncope recurrence rates. Electrophysiological parameters and heart rate variability (HRV) analysis were used to evaluate procedural response.


Procedural endpoints were achieved in all cases without any serious adverse events. Compared with the combined approach group, EAM-guided CNA was related to a shorter procedure and fluoroscopy times (p < 0.001). The mean number of ablation points in each anatomical segment was comparable between groups. The prodromal symptoms demonstrated a significant and comparable decrease after CNA. Median event-free survival was comparable between groups (χ2 = 0.03, p = 0.87). There was no new syncopal episode in any case at the end of 6-month follow-up. In the combined approach group, new syncope episodes occurred in two cases after 12-month follow-up. HRV parameters indicating parasympathetic activity were comparably decreased after ablation in both groups.


This pilot study shows that EAM-guided CNA strategy is feasible and safe in VVS patients resistant to conventional therapies.

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  1. Shen WK, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD, 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.

    Article  PubMed  Google Scholar 

  2. Wieling W, Jardine DL, de Lange FJ, Brignole M, Nielsen HB, Stewart J, et al. Cardiac output and vasodilation in the vasovagal response: an analysis of the classic papers. Heart Rhythm. 2016;13:798–805.

    Article  PubMed  Google Scholar 

  3. Varosy PD, Chen LY, Miller AL, Noseworthy PA, Slotwiner DJ, Thiruganasambandamoorthy V. Pacing as a treatment for Reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: a systematic review for the 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. Circulation. 2017;136:e123–35.

    Article  PubMed  Google Scholar 

  4. Randall WC, Milosavljevic M, Wurster RD, Geis GS, Ardell JL. Selective vagal innervation of the heart. Ann Clin Lab Sci. 1986;16:198–208.

    PubMed  CAS  Google Scholar 

  5. Randall WC, Ardell JL, O’Toole MF, Wurster RD. Differential autonomic control of SAN and AVN regions of the canine heart: structure and function. Prog Clin Biol Res. 1988;275:15–31.

    PubMed  CAS  Google Scholar 

  6. Chiou CW, Eble JN, Zipes DP. Efferent vagal innervation of the canine atria and sinus and atrioventricular nodes. The third fat pad. Circulation. 1997;95:2573–84.

    Article  PubMed  CAS  Google Scholar 

  7. Soejima K, Akaishi M, Mitamura H, Ogawa S, Sakurada H, Okazaki H, et al. Increase in heart rate after radiofrequency catheter ablation is mediated by parasympathetic nervous withdrawal and related to site of ablation. J Electrocardiol. 1997;30:239–46.

    Article  PubMed  CAS  Google Scholar 

  8. Pappone C, Stabile G, Oreto G, De Simone A, Rillo M, Mazzone P, et al. Inappropriate sinus tachycardia after radiofrequency ablation of para-Hisian accessory pathways. J Cardiovasc Electrophysiol. 1997;8:1357–65.

    Article  PubMed  CAS  Google Scholar 

  9. Pachon JC, Pachon EI, Pachon JC, Lobo TJ, Pachon MZ, Vargas RN, et al. “Cardioneuroablation”—new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace. 2005;7:1–13.

    Article  PubMed  Google Scholar 

  10. Scanavacca M, Hachul D, Pisani C, et al. Selective vagal denervation of the sinus and atrioventricular nodes, guided by vagal reflexes induced by high frequency stimulation, to treat refractory neurally mediated syncope. J Cardiovasc Electrophysiol. 2009;20:558–63.

    Article  PubMed  Google Scholar 

  11. Yao Y, Shi R, Wong T, Zheng L, Chen W, Yang L, et al. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol. 2012;5:279–86.

    Article  PubMed  Google Scholar 

  12. Rebecchi M, de Ruvo E, Strano S, Sciarra L, Golia P, Martino A, et al. Ganglionated plexi ablation in right atrium to treat cardioinhibitory neurocardiogenic syncope. J Interv Card Electrophysiol. 2012;34:231–5.

    Article  PubMed  Google Scholar 

  13. Debruyne P. Cardio-neuromodulation with a multielectrode irrigated catheter: a potential new approach for patients with cardio-inhibitory syncope. J Cardiovasc Electrophysiol. 2016;27:1110–3.

    Article  PubMed  Google Scholar 

  14. Lellouche N, Buch E, Celigoj A, Siegerman C, Cesario D, De Diego C, et al. Functional characterization of atrial electrograms in sinus rhythm delineates sites of parasympathetic innervation in patients with paroxysmal atrial fibrillation. J Am Coll Cardiol. 2007;50:1324–31.

    Article  PubMed  Google Scholar 

  15. Rivarola E, Hardy C, Sosa E, Hachul D, Furlan V, Raimundi F, et al. Selective atrial vagal denervation guided by spectral mapping to treat advanced atrioventricular block. Europace. 2016;18:445–9.

    Article  PubMed  Google Scholar 

  16. Zhao L, Jiang W, Zhou L, et al. Atrial autonomic denervation for the treatment of long-standing symptomatic sinus bradycardia in non-elderly patients. J Interv Card Electrophysiol. 2015;43:151–9.

    Article  PubMed  Google Scholar 

  17. Aksu T, Güler TE, Bozyel S, Özcan KS, Yalın K, Mutluer FO. Cardioneuroablation in the treatment of neurally mediated reflex syncope: a review of the current literature. Turk Kardiyol Dern Ars. 2017;45:33–41.

    PubMed  Google Scholar 

  18. Aksu T, Golcuk E, Yalin K, Guler TE, Erden I. Simplified Cardioneuroablation in the treatment of reflex syncope, functional AV block, and sinus node dysfunction. Pacing ClinElectrophysiol. 2016;39:42–53.

    Article  Google Scholar 

  19. Aksu T, Guler TE, Yalin K, Bozyel S. Vagal ganglia ablation: a little-known route in the treatment of vasovagal syncope. EP Lab Digest. 2017;17:26–7.

    Google Scholar 

  20. Brignole M, Menozzi C, Del Rosso A, Costa S, Gaggioli G, Bottoni N, et al. New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the presyncopal phase of the tilt test without and with nitroglycerin challenge. Vasovagal Syncope International Study Europace. 2000;2:66–76.

    PubMed  CAS  Google Scholar 

  21. Kenny RA, O'Shea D, Parry SW. The Newcastle protocols for head-up tilt table testing in the diagnosis of vasovagal syncope, carotid sinus hypersensitivity, and related disorders. Heart. 2000;83:564–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Aksu T, Güler TE, Mutluer FO, Oto MA. Vagal denervation in atrial fibrillation ablation: a comprehensive review. Anatol J Cardiol. 2017;18:142–8.

    PubMed  PubMed Central  Google Scholar 

  23. Sun W, Zheng L, Qiao Y, Shi R, Hou B, Wu L, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Aksu T, Guler TE, Yalin K, Mutluer FO, Calò L. Catheter ablation of bradyarrhythmia: from the beginning to the future. Am J Med Sci. 2018;355:252–65.

    Article  PubMed  Google Scholar 

  25. Pachon JC, Pachon EI, Pachon MZC, Lobo TJ, Pachon JC, Santillana TG. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace. 2011;13:1231–42.

    Article  PubMed  Google Scholar 

  26. Rivarola EW, Hachul D, Wu T, Pisani C, Hardy C, Raimundi F, et al. Targets and end points in cardiac autonomic denervation procedures. Circ Arrhythm Electrophysiol. 2017;10(2):e004638.

    Article  PubMed  Google Scholar 

  27. Chapleau MW, Sabharwal R. Methods of assessing vagus nerve activity and reflexes. Heart Fail Rev. 2011;16:109–27.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tomaino M, Romeo C, Vitale E, Kus T, Moya A, van Dijk N, et al. Physical counter-pressure maneuvers in preventing syncopal recurrence in patients older than 40 years with recurrent neurally mediated syncope: a controlled study from the third international study on Syncope of uncertain etiology (ISSUE-3). Europace. 2014;16:1515–20.

    Article  PubMed  Google Scholar 

  29. Tanaka K, Zlochiver K, Vikstrom KL, Yamazaki M, Moreno J, Klos M, et al. Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heat failure. Circ Res. 2007;101:839–47.

    Article  PubMed  CAS  Google Scholar 

  30. Jadidi AS, Cochet H, Shah AJ, Kim SJ, Duncan E, Miyazaki S, et al. Inverse relationship between fractionated electrograms and atrial fibrosis in persistent atrial fibrillation: combined magnetic resonance imaging and high-density mapping. J Am Coll Cardiol. 2013;62:802–12.

    Article  PubMed  Google Scholar 

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Correspondence to Tolga Aksu.

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Tolga Aksu has received a live case performance honorarium from Wokshop Registration Office of 21st Prague Workshop on Catheter Ablation. The other authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study, although for retrospective type of study formal consent is not required.

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Aksu, T., Guler, T.E., Mutluer, F.O. et al. Electroanatomic-mapping-guided cardioneuroablation versus combined approach for vasovagal syncope: a cross-sectional observational study. J Interv Card Electrophysiol 54, 177–188 (2019).

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  • Parasympathetic
  • Bradycardia
  • Vagal ganglia
  • Atrial fibrillation
  • Ganglionated plexi
  • Fat pad