Neuromodulation for the Management of Atrial Fibrillation—How to Optimize Patient Selection and the Procedural Approach

Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res. 2014;114(9):1453–68.

Article  CAS  PubMed  Google Scholar 

Iwasaki Y-k, Nishida K, Kato T, Nattel S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011;124(20):2264–74.

Article  CAS  PubMed  Google Scholar 

Armour JA. Potential clinical relevance of the ‘little brain’ on the mammalian heart. Exp Physiol. 2008;93(2):165–76.

Article  CAS  PubMed  Google Scholar 

Shivkumar K, Ajijola OA, Anand I, Armour JA, Chen PS, Esler M, et al. Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics. J Physiol. 2016;594(14):3911–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanna P, Buch E, Stavrakis S, Meyer C, Tompkins JD, Ardell JL, et al. Neuroscientific therapies for atrial fibrillation. Cardiovasc Res. 2021;117(7):1732–45. https://doi.org/10.1093/cvr/cvab172.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zafeiropoulos S, Doundoulakis I, Farmakis IT, Miyara S, Giannis D, Giannakoulas G, et al. Autonomic neuromodulation for atrial fibrillation following cardiac surgery: JACC review topic of the week. J Am Coll Cardiol. 2022;79(7):682–94. https://doi.org/10.1016/j.jacc.2021.12.010.

Article  PubMed  Google Scholar 

Jiang Z, Zhao Y, Tsai WC, Yuan Y, Chinda K, Tan J, et al. Effects of vagal nerve stimulation on ganglionated plexi nerve activity and ventricular rate in ambulatory dogs with persistent atrial fibrillation. JACC Clin Electrophysiol. 2018;4(8):1106–14. https://doi.org/10.1016/j.jacep.2018.05.003.

Article  PubMed  PubMed Central  Google Scholar 

Ardell JL, Cardinal R, Beaumont E, Vermeulen M, Smith FM, Andrew AJ. Chronic spinal cord stimulation modifies intrinsic cardiac synaptic efficacy in the suppression of atrial fibrillation. Auton Neurosci. 2014;186:38–44. https://doi.org/10.1016/j.autneu.2014.09.017.

Article  PubMed  PubMed Central  Google Scholar 

Stavrakis S, Humphrey MB, Scherlag B, Iftikhar O, Parwani P, Abbas M, et al. Low-level vagus nerve stimulation suppresses post-operative atrial fibrillation and inflammation: a randomized study. JACC Clin Electrophysiol. 2017;3(9):929–38. https://doi.org/10.1016/j.jacep.2017.02.019.

Article  PubMed  Google Scholar 

Stavrakis S, Humphrey MB, Scherlag BJ, Hu Y, Jackman WM, Nakagawa H, et al. Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation. J Am Coll Cardiol. 2015;65(9):867–75. https://doi.org/10.1016/j.jacc.2014.12.026.

Article  PubMed  PubMed Central  Google Scholar 

. Stavrakis S, Stoner JA, Humphrey MB, Morris L, Filiberti A, Reynolds JC, et al. TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): a randomized clinical trial. JACC Clin Electrophysiol. 2020;6(3):282–91. https://doi.org/10.1016/j.jacep.2019.11.008. This RCT indicates that chronic intermittent right-sided ta-VNS for 1 h daily with a frequency of 20 Hz and an amplitude adjusted individually to 1 mA below the discomfort threshold can significantly reduce AF burden over a 6-month period.

Article  PubMed  PubMed Central  Google Scholar 

Yu L, Scherlag BJ, Li S, Fan Y, Dyer J, Male S, et al. Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve: a noninvasive approach to treat the initial phase of atrial fibrillation. Heart Rhythm. 2013;10(3):428–35. https://doi.org/10.1016/j.hrthm.2012.11.019.

Article  PubMed  Google Scholar 

Yuan Y, Liu X, Wan J, Wong J, Bedwell AA, Persohn SA, et al. Subcutaneous nerve stimulation for rate control in ambulatory dogs with persistent atrial fibrillation. Heart Rhythm. 2019;16(9):1383–91. https://doi.org/10.1016/j.hrthm.2019.05.029.

Article  PubMed  PubMed Central  Google Scholar 

. Kulkarni K, Singh JP, Parks KA, Katritsis DG, Stavrakis S, Armoundas AA. Low-level tragus stimulation modulates atrial alternans and fibrillation burden in patients with paroxysmal atrial fibrillation. J Am Heart Assoc. 2021;10(12):e020865. https://doi.org/10.1161/JAHA.120.020865. This study introduces P-wave alternans as an ideal biomarker for evaluating treatment response following ta-VNS and thus optimizing patient selection. The early increase in this biomarker with acute ta-VNS is associated with a lower AF burden over 6 months.

Article  PubMed  PubMed Central  Google Scholar 

Kusayama T, Wan J, Yuan Y, Liu X, Li X, Shen C, et al. Effects of subcutaneous nerve stimulation with blindly inserted electrodes on ventricular rate control in a canine model of persistent atrial fibrillation. Heart Rhythm. 2021;18(2):261–70. https://doi.org/10.1016/j.hrthm.2020.09.009.

Article  PubMed  Google Scholar 

Bettoni M, Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation. 2002;105(23):2753–9.

Article  PubMed  Google Scholar 

Po SS, Scherlag BJ, Yamanashi WS, Edwards J, Zhou J, Wu R, et al. Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein-atrial junctions. Heart Rhythm. 2006;3(2):201–8. https://doi.org/10.1016/j.hrthm.2005.11.008.

Article  PubMed  Google Scholar 

Patterson E, Po SS, Scherlag BJ, Lazzara R. Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation. Heart Rhythm. 2005;2(6):624–31. https://doi.org/10.1016/j.hrthm.2005.02.012.

Article  PubMed  Google Scholar 

Scherlag BJ, Yamanashi W, Patel U, Lazzara R, Jackman WM. Autonomically induced conversion of pulmonary vein focal firing into atrial fibrillation. J Am Coll Cardiol. 2005;45(11):1878–86. https://doi.org/10.1016/j.jacc.2005.01.057.

Article  PubMed  Google Scholar 

Yu L, Scherlag BJ, Sha Y, Li S, Sharma T, Nakagawa H, et al. Interactions between atrial electrical remodeling and autonomic remodeling: how to break the vicious cycle. Heart Rhythm. 2012;9(5):804–9. https://doi.org/10.1016/j.hrthm.2011.12.023.

Article  PubMed  Google Scholar 

Shu C, Huang W, Zeng Z, He Y, Luo B, Liu H, et al. Connexin 43 is involved in the sympathetic atrial fibrillation in canine and canine atrial myocytes. Anatol J Cardiol. 2017;18(1):3–9. https://doi.org/10.14744/AnatolJCardiol.2017.7602.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu L, Nattel S. Differing sympathetic and vagal effects on atrial fibrillation in dogs: role of refractoriness heterogeneity. Am J Physiol Heart Circ Physiol. 1997;273(2):H805–H16.

Article  CAS  Google Scholar 

Linz D, Schotten U, Neuberger H-R, Böhm M, Wirth K. Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation. Heart Rhythm. 2011;8(9):1436–43.

Article  PubMed  Google Scholar 

Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger H-R, Wirth K, et al. Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension. 2012;60(1):172–8.

Article  CAS  PubMed  Google Scholar 

Rajendran PS, Hadaya J, Khalsa SS, Yu C, Chang R, Shivkumar K. The vagus nerve in cardiovascular physiology and pathophysiology: from evolutionary insights to clinical medicine. In: Seminars in Cell & Developmental Biology. Elsevier; 2023.

Google Scholar 

Sha Y, Scherlag BJ, Yu L, Sheng X, Jackman WM, Lazzara R, et al. Low-level right vagal stimulation: anticholinergic and antiadrenergic effects. J Cardiovasc Electrophysiol. 2011;22(10):1147–53. https://doi.org/10.1111/j.1540-8167.2011.02070.x.

Article  PubMed  Google Scholar 

Shen MJ, Shinohara T, Park HW, Frick K, Ice DS, Choi EK, et al. Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. Circulation. 2011;123(20):2204–12. https://doi.org/10.1161/circulationaha.111.018028.

Article  PubMed  PubMed Central  Google Scholar 

Stavrakis S, Scherlag BJ, Fan Y, Liu Y, Mao J, Varma V, et al. Inhibition of atrial fibrillation by low-level vagus nerve stimulation: the role of the nitric oxide signaling pathway. J Interv Card Electrophysiol. 2013;36(3):199–208. https://doi.org/10.1007/s10840-012-9752-8.

Article  PubMed  Google Scholar 

Yu L, Scherlag BJ, Li S, Sheng X, Lu Z, Nakagawa H, et al. Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia. J Cardiovasc Electrophysiol. 2011;22(4):455–63. https://doi.org/10.1111/j.1540-8167.2010.01908.x.

Article  PubMed  Google Scholar 

Sheng X, Scherlag BJ, Yu L, Li S, Ali R, Zhang Y, et al. Prevention and reversal of atrial fibrillation inducibility and autonomic remodeling by low-level vagosympathetic nerve stimulation. J Am Coll Cardiol. 2011;57(5):563–71.

Article  PubMed  Google Scholar 

Yuan Y, Jiang Z, He Y, Ding F-B, Ding S-A, Yang Y, et al. Continuous vagal nerve stimulation affects atrial neural remodeling and reduces atrial fibrillation inducibility in rabbits. Cardiovasc Pathol. 2015;24(6):395–8. https://doi.org/10.1016/j.carpath.2015.08.005.

Article  PubMed  Google Scholar 

Chinda K, Tsai W-C, Chan Y-H, Lin AY-T, Patel J, Zhao Y, et al. Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs. Heart Rhythm. 2016;13(3):771–80.

Article  PubMed  Google Scholar 

Butt MF, Albusoda A, Farmer AD, Aziz Q. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020;236(4):588–611.

Article  PubMed  Google Scholar 

Frangos E, Ellrich J, Komisaruk BR. Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimul. 2015;8(3):624–36.

Article  PubMed  Google Scholar 

Chen M, Zhou X, Liu Q, Sheng X, Yu L, Wang Z, et al. Left-sided noninvasive vagus nerve stimulation suppresses atrial fibrillation by upregulating atrial gap junctions in canines. J Cardiovasc Pharmacol. 2015;66(6):593–9. https://doi.org/10.1097/fjc.0000000000000309.

Article  CAS  PubMed  Google Scholar 

Chen M, Yu L, Liu Q, Wang Z, Wang S, Jiang H, et al. Low level tragus nerve stimulation is a non-invasive approach for anti-atrial fibrillation via preventing the loss of connexins. Int J Cardiol. 2015;179:144–5. https://doi.org/10.1016/j.ijcard.2014.10.114.

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