Selective Modulation of the Cardiac Autonomic Nervous System: A New Therapeutic Strategy for Cardioinhibitory Vasovagal Syncope

Main Article Content

Win Kuang Shen, MD Nway L. Ko Ko, MBBS Gurukripa N. Kowlgi, MBBS Juan C. Zerpa A., MS José C. Pachón, MD Enrique I. Pachon-M Win-Kuang Shen, MD


Vasovagal syncope (VVS) is the most common type of syncope. The overall prognosis of VVS is usually benign, although the quality of life can be affected when syncope is recurrent and refractory to conventional therapy. Multiple treatment options exist for patients with recurrent VVS, although the effect is modest. In this focused review, we briefly discussed the plausible pathophysiological mechanisms of VVS. We used three case examples to update the current state of cardioneuroablation (CNA) in patients with recurrent cardioinhibitory response as a potential therapeutic option. This article includes review of studies and reports on CNA summarizing the principles of this therapeutic approach; various ways of mapping to localize the parasympathetic ganglionic plexi for ablation; description of technique of extra-cardiac vagal stimulation to confirm parasympathetic denervation of the heart as well as the end points and outcomes of the reported studies. Moreover, we reviewed the pros, cons, gaps, and future directions of this potential therapeutic option in treating patients with VVS.

Article Details

How to Cite
SHEN, Win Kuang et al. Selective Modulation of the Cardiac Autonomic Nervous System: A New Therapeutic Strategy for Cardioinhibitory Vasovagal Syncope. Medical Research Archives, [S.l.], v. 11, n. 7.1, july 2023. ISSN 2375-1924. Available at: <>. Date accessed: 16 july 2024. doi:
Research Articles


1. Márquez, M.F., et al., Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors. Medwave, 2016. 16(Suppl4): p. e6824.
2. Alboni, P., The different clinical presentations of vasovagal syncope. Heart, 2015. 101(9): p. 674-8.
3. Brignole, M., et al., New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the pre-syncopal phase of the tilt test without and with nitroglycerin challenge. Vasovagal Syncope International Study. Europace, 2000. 2(1): p. 66-76.
4. Maloney, J.D., et al., Malignant vasovagal syncope: prolonged asystole provoked by head-up tilt. Case report and review of diagnosis, pathophysiology, and therapy. Cleve Clin J Med, 1988. 55(6): p. 542-8.
5. Sheldon, R.S., et al., 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm, 2015. 12(6): p. e41-63.
6. Shen, W.K., 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. Heart Rhythm, 2017. 14(8): p. e155-e217.
7. Brignole, M., et al., [2018 ESC Guidelines for the diagnosis and management of syncope]. Kardiol Pol, 2018. 76(8): p. 1119-1198.
8. Garcia, A., et al., Cardioinhibitory syncope: from pathophysiology to treatment-should we think on cardioneuroablation? J Interv Card Electrophysiol, 2020. 59(2): p. 441-461.
9. Yao, Y., et al., Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol, 2012. 5(2): p. 279-86.
10. Pachon, J.C., et al., Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace, 2011. 13(9): p. 1231-42.
11. Debruyne, P. and W. Wijns, Cardio-Neuromodulation: The Right-Sided Approach. JACC Clin Electrophysiol, 2017. 3(9): p. 1056-1057.
12. Reid, I.A., Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol, 1992. 262(6 Pt 1): p. E763-78.
13. Pachon, J.C., et al., "Cardioneuroablation"--new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace, 2005. 7(1): p. 1-13.
14. Sun, W., 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).
15. Aksu, T., et al., Simplified Cardioneuroablation in the Treatment of Reflex Syncope, Functional AV Block, and Sinus Node Dysfunction. Pacing Clin Electrophysiol, 2016. 39(1): p. 42-53.
16. Pachon, M.J., et al., Simplified Method for Vagal Effect Evaluation in Cardiac Ablation and Electrophysiological Procedures. JACC Clin Electrophysiol, 2015. 1(5): p. 451-460.
17. Hu, F., et al., Right anterior ganglionated plexus: The primary target of cardioneuroablation? Heart Rhythm, 2019. 16(10): p. 1545-1551.
18. Stirrup, J., et al., Hybrid solid-state SPECT/CT left atrial innervation imaging for identification of left atrial ganglionated plexi: Technique and validation in patients with atrial fibrillation. J Nucl Cardiol, 2020. 27(6): p. 1939-1950.
19. Chen, W., et al., Extracardiac Vagal Stimulation-Assisted Cardioneuroablation: Dynamically Evaluating the Impact of Sequential Ganglionated Plexus Ablation on Vagal Control of SAN and AVN in Patients with Sinoatrial Node Dysfunction. J Cardiovasc Dev Dis, 2022. 9(6).
20. Pachon, M.J., et al., A new treatment for atrial fibrillation based on spectral analysis to guide the catheter RF-ablation. Europace, 2004. 6(6): p. 590-601.
21. Pachon, M.E., et al., Relation of Fractionated Atrial Potentials With the Vagal Innervation Evaluated by Extracardiac Vagal Stimulation During Cardioneuroablation. Circ Arrhythm Electrophysiol, 2020. 13(4): p. e007900.
22. Romanov, A., et al., Visualization and ablation of the autonomic nervous system corresponding to ganglionated plexi guided by D-SPECT 123I-mIBG imaging in patient with paroxysmal atrial fibrillation. Clinical Research in Cardiology, 2016. 106.
23. Vandenberk, B., et al., Cardioneuroablation for vasovagal syncope: A systematic review and meta-analysis. Heart Rhythm, 2022.
24. Aksu, T., et al., Catheter Ablation of Bradyarrhythmia: From the Beginning to the Future. Am J Med Sci, 2018. 355(3): p. 252-265.
25. Kim, D.T., et al., Sympathetic nerve sprouting after orthotopic heart transplantation. J Heart Lung Transplant, 2004. 23(12): p. 1349-58.
26. Gallego-Page, J.C., et al., Re-innervation after heart transplantation: a multidisciplinary study. J Heart Lung Transplant, 2004. 23(6): p. 674-82.
27. Carvalho, M.S., et al., Prognostic Value of a Very Prolonged Asystole during Head-Up Tilt Test. Pacing Clin Electrophysiol, 2015. 38(8): p. 973-9.
28. Sahota, I.S., et al., Clusters, Gaps, and Randomness: Vasovagal Syncope Recurrence Patterns. JACC Clin Electrophysiol, 2017. 3(9): p. 1046-1053.
29. Sheldon, R.S., et al., Worsening of symptoms before presentation with vasovagal syncope. J Cardiovasc Electrophysiol, 2007. 18(9): p. 954-9.
30. Sahota, I., R. Sheldon, and P. Pournazari, Clinical improvement of vasovagal syncope in the absence of specific therapies: The Seinfeld effect. Cardiol J, 2014. 21(6): p. 637-42.
31. Sharma, G., et al., Effect of Yoga on Clinical Outcomes and Quality of Life in Patients With Vasovagal Syncope (LIVE-Yoga). JACC Clin Electrophysiol, 2022. 8(2): p. 141-149.