Clinical Autonomic Research

, Volume 29, Issue 2, pp 183–194 | Cite as

Cardiovascular autonomic effects of vagus nerve stimulation

  • Iñigo Garamendi-RuizEmail author
  • Juan Carlos Gómez-Esteban


The vagus nerve is responsible for the parasympathetic innervation of the major thoracic and abdominal organs. It also carries sensory afferent fibres from these viscera and reaches different brain structures. These connections have proven useful in the treatment of different diseases. Afferent stimulation of the left vagus nerve is used to treat epilepsy and major depression, and stimulation of the right vagus nerve is being tried for the treatment of heart failure. The device used for the therapy delivers intermittent stimuli. It is indicated worldwide for the treatment of drug-resistant epilepsy in patients who are not appropriate candidates for respective surgery. It has also received approval for the treatment of major depression, obesity and episodic cluster headache by the Food and Drug Administration. Randomised controlled trials and prospective studies have confirmed the efficacy and safety of this therapy in epilepsy. Nevertheless, sporadic cases of ventricular asystole have been reported. To evaluate the effect of vagus nerve stimulation therapy on the autonomic nervous system, different studies that assess heart function and blood pressure changes have been conducted, although the methods employed were not homogeneous. These studies have found subtle or no significant changes in heart rate variability and blood pressure in epileptic patients. Moreover, this therapy may reduce the risk of one of the most lethal conditions in epilepsy—sudden unexpected death.


Vagus nerve stimulation Heart failure Epilepsy Autonomic system 



We would like to acknowledge the contributions of Dr Iñigo Gabilondo (PhD) of the Biocruces Health Research Institute and Dr Lara Galbarriatu of the Neurosurgery Department of the Cruces University Hospital.

Compliance with ethical standards

Conflict of interest

This study did not receive specific grants from any funding agencies in the public, commercial or non-profit sectors. None of the authors have any conflict of interest to disclose.


  1. 1.
    Krahl SE (2012) Vagus nerve stimulation for epilepsy: a review of the peripheral mechanisms. Surg Neurol Int 3:S47–S52. doi: 10.4103/2152-7806.103015 CrossRefGoogle Scholar
  2. 2.
    Foley JO, DuBois F (1937) Quantitative studies of the vagus nerve in the cat. I. The ratio of sensory and motor fibers. J Comp Neurol 67:49–97. doi: 10.1002/cne.900670104 CrossRefGoogle Scholar
  3. 3.
    Krahl SE, Clark KB (2012) Vagus nerve stimulation for epilepsy: a review of the central mechanisms. Surg Neurol Int 3:255–259. doi: 10.4103/2152-7806.103015 CrossRefGoogle Scholar
  4. 4.
    Agostini E, Chinnock JE, Daly MD, Murray JG (1957) Functional and histological studies of the vagus nerve and its branches to the heart, lungs, and abdominal viscera in the cat. J Physiol 135:182–205CrossRefGoogle Scholar
  5. 5.
    Verlinden TJM, Rijkers K (2016) Morphology of the human cervical vagus nerve: implications for vagus nerve stimulation treatment. Acta Neurol Scand 133:173–182. doi: 10.1111/ane.12462 CrossRefGoogle Scholar
  6. 6.
    Randall WC, Milosavljevic M, Wurster RD, Geis GS, Ardell JL (1986) Selective vagal innervation of the heart. Ann Clin Lab Sci 1986:198–208Google Scholar
  7. 7.
    Ben-Menachem E, Revesz D, Simon BJ, Silberstein S (2015) Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol 22:1260–1268. doi: 10.1111/ene.12629 CrossRefGoogle Scholar
  8. 8.
    Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH, Donner E, French JA, Gil-Nagel A, Hesdorffer DC, Smithson WH, Spitz MC, Walczak TS, Sander JW, Ryvlin P (2017) Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 88:1674–1680. doi: 10.1212/WNL.0000000000003685 CrossRefGoogle Scholar
  9. 9.
    Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51:1069–1077. doi: 10.1111/j.1528-1167.2009.02397 CrossRefGoogle Scholar
  10. 10.
    Ben-Menachem E (2002) Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol 1:477–478. doi: 10.1016/S1474-4422(02)00220-X CrossRefGoogle Scholar
  11. 11.
    Giordano F, Zicca A, Barba C, Guerrini R, Genitori L (2017) Vagus nerve stimulation: surgical technique of implantation and revision and related morbidity. Epilepsia 58:S85–S90. doi: 10.1111/epi.13678 CrossRefGoogle Scholar
  12. 12.
    Tarver WB, George RE, Maschino SE (1992) Clinical experience with a helical bipolar stimulating lead. Pacing Clin Electrophysiol 15:1545–1556. doi: 10.1111/j.1540-8159.1992.tb02933.x CrossRefGoogle Scholar
  13. 13.
    Labiner DM, Ahern GL (2007) Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings. Acta Neurol Scand 115:23–33. doi: 10.1111/j.1600-0404.2006.00732.x CrossRefGoogle Scholar
  14. 14.
    DeGiorgio C, Heck C, Bunch S, Britton J, Green P, Lancman M, Murphy J, Olejniczak P, Shih J, Arrambide S, Soss J (2005) Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms. Neurology 65:317–319. doi: 10.1212/01.wnl.0000168899.11598.00 CrossRefGoogle Scholar
  15. 15.
    Liporace J, Hucko D, Morrow R, Barolat G, Nei M, Schnur J, Sperling M (2001) Vagal nerve stimulation: adjustments to reduce painful side effects. Neurology 57:885–886. doi: 10.1212/WNL.57.5.885 CrossRefGoogle Scholar
  16. 16.
    Boon P, Vonck K, van Rijckevorsel K, El Tahry R, Elger CE, Mullatti M, Schulze-Bonhage A, Wagner L, Diehl B, Hamer H, Reuber M, Kostov H, Legros B, Noachtar S, Weber YG, Coenen VA, Rooijakkers V, Schijns OEMG, Selway R, Van Roost D, Eggleston KS, Van Grunderbeek W, Jayewardene AK, McGuire RM (2015) A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. Seizure 32:52–61. doi: 10.1016/j.seizure.2015.08.011 CrossRefGoogle Scholar
  17. 17.
    McGregor A, Wheless J, Baumgartner J, Bettis D (2005) Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia 46:91–96. doi: 10.1111/j.0013-9580.2005.16404.x CrossRefGoogle Scholar
  18. 18.
    Navas M, García Navarrete A, Pascual JM, Carrasco R, Núñez JA, Shakur SF, Pastor J, Sola RG (2010) Treatment of refractory epilepsy in adult patients with right-sided vagus nerve stimulation. Epilepsy Res 90:1–7. doi: 10.1016/j.eplepsyres.2010.04.007 CrossRefGoogle Scholar
  19. 19.
    Bauer S, Baier H, Baumgartner C, Bohlmann K, Fauser S, Graf W, Hillenbrand B, Hirsch M, Last C, Lerche H, Mayer T, Schulze-Bonhage A, Steinhoff BJ, Weber Y, Hartlep A, Rosenow F, Hamer HM (2016) Transcutaneous vagus nerve stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02). Brain Stimul 9:356–363. doi: 10.1016/j.brs.2015.11.003 CrossRefGoogle Scholar
  20. 20.
    He W, Jing X, Wang X, Rong P, Li L, Shi H, Shang H, Wang Y, Zhang J, Zhu B (2013) Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial. Epilepsy Behav 28:343–346. doi: 10.1016/j.yebeh.2013.02.001 CrossRefGoogle Scholar
  21. 21.
    Stefan H, Kreiselmeyer G, Kerling F, Kurzbuch K, Rauch C, Heers M, Kasper BS, Hammen T, Rzonsa M, Pauli E, Ellrich J, Graf W, Hopfengärtner R (2012) Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia 53:e115–e118. doi: 10.1111/j.1528-1167.2012.03492.x CrossRefGoogle Scholar
  22. 22.
    Vonck K, Van Laere K, Dedeurwaerdere S, Caemaert J, De Reuck J, Boon P (2001) The mechanism of action of vagus nerve stimulation for refractory epilepsy. J Clin Neurophysiol 18:394–401CrossRefGoogle Scholar
  23. 23.
    Krahl SE, Senanayake SS, Handforth A (2001) Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats. Epilepsia 42:586–589. doi: 10.1046/j.1528-1157.2001.09700.x CrossRefGoogle Scholar
  24. 24.
    Krahl SF, Clark KB, Smith DC et al (1998) Locus coeruleus lesions suppress the seizure attenuating effects of vagus nerve stimulation. Epilepsia 39:709–714. doi: 10.1111/j.1528-1157.1998.tb01155.x CrossRefGoogle Scholar
  25. 25.
    Henry TR (2002) Therapeutic mechanisms of vagus nerve stimulation. Neurology 59(Suppl 4):S3–S14. doi: 10.1212/WNL.59.6_suppl_4.S3 CrossRefGoogle Scholar
  26. 26.
    Jaseja H (2010) EEG-desynchronization as the major mechanism of anti-epileptic action of vagal nerve stimulation in patients with intractable seizures: clinical neurophysiological evidence. Med Hypotheses 74:855–856. doi: 10.1016/j.mehy.2009.11.031 CrossRefGoogle Scholar
  27. 27.
    The Vagus Nerve Stimulation Study Group (1995) A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 45:224–230. doi: 10.1212/WNL.45.2.224 CrossRefGoogle Scholar
  28. 28.
    Handforth A, DeGiorgio CM, Schachter SC, Uthman BM et al (1998) Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51:48–55. doi: 10.1212/WNL.51.1.48 CrossRefGoogle Scholar
  29. 29.
    Morris GL, Mueller WM, Vagus Nerve Stimulation Study Group EO1–EO5 (1999) Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 53:1731–1735. doi: 10.1212/WNL.53.8.1731 CrossRefGoogle Scholar
  30. 30.
    DeGiorgio CM, Schachter SC, Handforth A, Salinsky M, Thompson J, Uthman YB, Reed R, Collins S, Tecoma E, Morris LG, Vaughn B, Naritoku DK, Henry T, Labar D, Gilmartin R, Labiner D, Osorio I, Ristanovic R, Jones J, Murphy J, Ney G, Wheless J, Lewis P, Hecket C (2000) Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 41:1195–1200. doi: 10.1111/j.1528-1157.2000.tb00325.x CrossRefGoogle Scholar
  31. 31.
    De Herdt V, Boon P, Ceulemans B, Hauman H, Lagae L, Legros B, Sadzot B, Van Bogaert P, van Rijckevorsel K, Verhelst H, Vonck K (2007) Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 11:261–269. doi: 10.1016/j.ejpn.2007.01.008 CrossRefGoogle Scholar
  32. 32.
    Elliott RE, Morsi A, Kalhorn SP, Marcus J, Sellin J, Kang M, Silverberg A, Rivera E, Geller E, Carlson C, Devinsky O, Doyle WK (2011) Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav 20:57–63. doi: 10.1016/j.yebeh.2010.10.017 CrossRefGoogle Scholar
  33. 33.
    Galbarriatu L, Pomposo I, Aurrecoechea J, Marinas A, Agúndez M, Gómez JC, Acera MA, Martínez MJ, Valle E, Maestro I, Mateos B, Cabrera A, Fernández J, Iturri F, Garamendi I (2015) Vagus nerve stimulation therapy for treatment-resistant epilepsy: a 15-year experience at a single institution. Clin Neurol Neurosurg 137:89–93. doi: 10.1016/j.clineuro.2015.06.023 CrossRefGoogle Scholar
  34. 34.
    McHugh JC, Singh HW, Phillips J, Murphy K, Doherty CP, Delanty N (2007) Outcome measurement after vagal nerve stimulation therapy: proposal of a new classification. Epilepsia 48:375–378. doi: 10.1111/j.1528-1167.2006.00931.x CrossRefGoogle Scholar
  35. 35.
    Helmers SL, Wheless JW, Frost M et al (2001) Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol 16:843–848. doi: 10.1177/08830738010160111101 CrossRefGoogle Scholar
  36. 36.
    Vonck K, Thadani V, Gilbert K, Dedeurwaerdere S, De Groote L, De Herdt V, Goossens L, Gossiaux F, Achten E, Thiery E, Vingerhoets G, Van Roost D, Caemaert J, De Reuck J, Roberts D, Williamson P, Boon P (2004) Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. J Clin Neurophysiol 21:283–289CrossRefGoogle Scholar
  37. 37.
    Fernandez L, Gedela S, Tamber M, Sogawa Y (2015) Vagus nerve stimulation in children less than 3 years with medically intractable epilepsy. Epilepsy Res 112:37–42. doi: 10.1016/j.eplepsyres.2015.02.009 CrossRefGoogle Scholar
  38. 38.
    Ryvlin P, Gilliam G, Nguyen DK, Colicchio G, Iudice A, Tinuper P, Zamponi N, Aguglia U, Wagner L, Minotti L, Stefan H, Boon P, Sadler M, Benna P, Raman P, Perucca E (2014) The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia 55:893–900. doi: 10.1111/epi.12611 CrossRefGoogle Scholar
  39. 39.
    Elliott RE, Morsi A, Tanweer O, Grobelny B, Geller E, Carlson C, Devinsky O, Doyle WK (2011) Efficacy of vagus nerve stimulation over time: review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS N10 years. Epilepsy Behav 20:478–483. doi: 10.1016/j.yebeh.2010.12.042 CrossRefGoogle Scholar
  40. 40.
    Ardesch JJ, Buschman HP, Wagener-Schimmel LJ, van der Aa HE, Hageman G (2007) Vagus nerve stimulation for medically refractory epilepsy: a long-term follow-up study. Seizure 16:579–585. doi: 10.1016/j.seizure.2007.04.005 CrossRefGoogle Scholar
  41. 41.
    Winston KR, Levisohn P, Miller BR, Freeman J (2001) Vagal nerve stimulation for status epilepticus. Pediatr Neurosurg 34:190–192. doi: 10.1159/000056018 CrossRefGoogle Scholar
  42. 42.
    Patwardhan RV, Dellabadia J Jr, Rashidi M, Grier L, Nanda A (2005) Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report. Surg Neurol 64:170–173. doi: 10.1016/j.surneu.2004.11.026 CrossRefGoogle Scholar
  43. 43.
    Sierra-Marcos A, Maestro I, Rodríguez-Osorio X, Miró J, Donaire A, Aparicio J, Rumiá J, Forcadas M, Garamendi I, Pardo J, López J, Prieto Á, Plans G, Falip M, Carreño M (2012) Successful outcome of episodes of status epilepticus after vagus nerve stimulation: a multicenter study. Eur J Neurol 19:1219–1223. doi: 10.1111/j.1468-1331.2012.03707.x CrossRefGoogle Scholar
  44. 44.
    Annegers JF, Coan SP, Hauser WA, Leestma J (2000) Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia 41:549–553. doi: 10.1111/j.1528-1157.2000.tb00208.x CrossRefGoogle Scholar
  45. 45.
    Tatum WO IV, Moore DB, Stecker MM, Baltuch GH, French JA, Ferreira JA, Carney PM, Labar DR, Vale FL (1999) Ventricular asystole during vagus nerve stimulation for epilepsy in humans. Neurology 52:1267–1269. doi: 10.1212/WNL.52.6.1271 CrossRefGoogle Scholar
  46. 46.
    Ardesch JJ, Buschman HP, van der Burgh PH, Wagener-Schimmel LJ, van der Aa HE, Hageman G (2007) Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Clin Neurol Neurosurg 109:849–852. doi: 10.1016/j.clineuro.2007.07.024 CrossRefGoogle Scholar
  47. 47.
    Schuurman PR, Beukers RJ (2009) Ventricular asystole during vagal nerve stimulation. Epilepsia 50:967–968. doi: 10.1111/j.1528-1167.2008.01907.x CrossRefGoogle Scholar
  48. 48.
    Amark P, Stodberg T, Wallstedt L (2007) Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia 48:1023–1024. doi: 10.1111/j.1528-1167.2007.01023.x CrossRefGoogle Scholar
  49. 49.
    Borusiak P, Zilbauer M, Cagnoli S, Heldmann M, Jenke A (2009) Late-onset cardiac arrhythmia associated with vagus nerve stimulation. J Neurol 256:1578–1580. doi: 10.1007/s00415-009-5162-y CrossRefGoogle Scholar
  50. 50.
    Iriarte J, Urrestarazu E, Alegre M et al (2009) Late-onset periodic asystolia during vagus nerve stimulation. Epilepsia 50:928–932. doi: 10.1111/j.1528-1167.2008.01918.x CrossRefGoogle Scholar
  51. 51.
    Shankar R, Olotu VO, Cole N, Sullivan H, Joryet C (2013) Case report: vagal nerve stimulation and late onset asystole. Seizure 22:312–314. doi: 10.1016/j.seizure.2012.12.011 CrossRefGoogle Scholar
  52. 52.
    Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE (2000) Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res 42:203–210. doi: 10.1016/S0920-1211(00)00181-9 CrossRefGoogle Scholar
  53. 53.
    Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR (2000) A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy Behav 1:93–99. doi: 10.1006/ebeh.2000.0046 CrossRefGoogle Scholar
  54. 54.
    Grimonprez A, Raedt A, Portelli J, Dauwe I, Larsen LE, Bouckaert C, Delbeke J, Carrette E, Meurs A, De Herdt V, Boon P, Vonck K (2015) The antidepressant-like effect of vagus nerve stimulation is mediated through the locus coeruleus. J Psychiatr Res 68:1–7. doi: 10.1016/j.jpsychires.2015.05.002 CrossRefGoogle Scholar
  55. 55.
    Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG (2005) Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 58:347–354. doi: 10.1016/j.biopsych.2005.05.025 CrossRefGoogle Scholar
  56. 56.
    Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM et al (2005) Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry 58:355–363. doi: 10.1016/j.biopsych.2005.05.024 CrossRefGoogle Scholar
  57. 57.
    Ikramuddin S, Blackstone RP, Brancatisano A, Toouli J, Shah SN, Wolfe BM, Fujioka K, Maher JW, Swain J, Que FG, Morton JM, Leslie DB, Brancatisano R, Kow L, O’Rourke RW, Deveney C, Takata M, Miller CJ, Knudson MB, Tweden KS, Shikora SA, Sarr MG, Billington CJ (2014) Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial. JAMA 312:915–922. doi: 10.1001/jama.2014.10540 CrossRefGoogle Scholar
  58. 58.
    Apovian CM, Shah SN, Wolfe BM, Ikramuddin S, Miller CJ, Tweden KS, Billington CJ, Shikora SA (2017) Two-year outcomes of vagal nerve blocking (vBloc) for the treatment of obesity in the recharge trial. Obes Surg 27:169–176. doi: 10.1007/s11695-016-2325-7 CrossRefGoogle Scholar
  59. 59.
    Gaul C, Diener HC, Silver N, Magis D, Reuter U, Andersson A, Liebler EJ, Straube A, on behalf of PREVA Study Group (2016) Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia 36:534–546. doi: 10.1177/0333102415607070 CrossRefGoogle Scholar
  60. 60.
    Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, Liebler EJ, Rubenstein Engel E, Tepper SJ, on behalf of ACT1 Study Group (2016) Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache 56:1317–1332. doi: 10.1111/head.12896 CrossRefGoogle Scholar
  61. 61.
    Klein HU, De Ferrari GM (2010) Vagus nerve stimulation: a new approach to reduce heart failure. Cardiol J 17:638–643Google Scholar
  62. 62.
    De Ferrari GM, Crijns HJGM, Borggrefe M, Milasinovic G, Smid J, Zabel M, Gavazzi A, Sanzo A, Dennert R, Kuschyk J, Raspopovic S, Klein H, Swedberg K, Schwartz PJ, for the CardioFit Multicenter Trial Investigators (2011) Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J 32:847–855. doi: 10.1093/eurheartj/ehq424 CrossRefGoogle Scholar
  63. 63.
    Zannad F, De Ferrari GM, Tuinenburg AE, Wright D, Brugada J, Butter C, Klein H, Stolen C, Meyer S, Stein KM, Ramuzat A, Schubert B, Daum D, Neuzil P, Botman C, Castel MA, D’Onofrio A, Solomon SD, Wold N, Ruble SB (2015) Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J 36:425–433. doi: 10.1093/eurheartj/ehu345 CrossRefGoogle Scholar
  64. 64.
    Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS (2014) Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Cardiac Fail 20:808–816. doi: 10.1016/j.cardfail.2014.08.009 CrossRefGoogle Scholar
  65. 65.
    Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS (2016) Extended follow-up of patients with heart failure receiving autonomic regulation therapy in the ANTHEM-HF study. J Cardiac Fail 22:639–642. doi: 10.1016/j.cardfail.2015.11.002 CrossRefGoogle Scholar
  66. 66.
    Libbus I, Nearing BD, Amurthur B, KenKnight BH, Verrier RL (2016) Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study. Heart Rhythm 13:721–728. doi: 10.1016/j.hrthm.2015.11.030 CrossRefGoogle Scholar
  67. 67.
    Gold MR, Van Veldhuisen DJ, Hauptman PJ, Borggrefe M, Kubo SH, Lieberman RA, Milasinovic G, Berman BJ, Djordjevic S, Neelagaru S, Schwartz PJ, Starling RC, Mann DL (2016) Vagus nerve stimulation for the treatment of heart failure: the INOVATE-HF trial. J Am Coll Cardiol 68:149–158. doi: 10.1016/j.jacc.2016.03.525 CrossRefGoogle Scholar
  68. 68.
    Beaumont E, Southerland EM, Hardwick JC, Wright GL, Ryan S, Li Y, KenKnight BH, Armour JA, Ardell JL (2015) Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction. Am J Physiol Heart Circ Physiol 309:H1198–H1206. doi: 10.1152/ajpheart.00393.2015 CrossRefGoogle Scholar
  69. 69.
    Tomson T, Ericson M, Ihrman C, Lindblad LE (1998) Heart rate variability in patients with epilepsy. Epilepsy Res 30:77–83. doi: 10.1016/S0920-1211(97)00094-6 CrossRefGoogle Scholar
  70. 70.
    Strzelczyk A, Adjei P, Scott CA, Bauer S, Rosenow F, Walker MC, Surges R (2012) Postictal increase in T-wave alternans after generalized tonic–clonic seizures. Epilepsia 52:2112–2117. doi: 10.1111/j.1528-1167.2011.03266.x CrossRefGoogle Scholar
  71. 71.
    Kamath MV, Upton ARM, Talalla A, Fallen EL (1992) Neurocardiac responses to vagoafferent electrostimulation in humans. Pacing Clin Electrophysiol 15:1581–1587. doi: 10.1111/j.1540-8159.1992.tb02937.x CrossRefGoogle Scholar
  72. 72.
    Setty AB, Vaughn BV, Quint SR, Robertson KR, Messenheimer JA (1998) Heart period variability during vagal nerve stimulation. Seizure 7:213–217. doi: 10.1016/S1059-1311(98)80038-1 CrossRefGoogle Scholar
  73. 73.
    Frei MG, Osorio I (2001) Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans. Epilepsia 42:1007–1016. doi: 10.1046/j.1528-1157.2001.0420081007.x CrossRefGoogle Scholar
  74. 74.
    Galli R, Limbruno U, Pizzanelli C, Giorgi FS, Lutzemberger L, Strata G, Pataleo L, Mariani M, Iudice A, Murri L (2003) Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation. Auton Neurosci 107:52–59. doi: 10.1016/S1566-0702(03)00081-X CrossRefGoogle Scholar
  75. 75.
    Ronkainen E, Korpelainen JT, Heikkinen E, Myllylä VV, Huikuri HV, Isojärvi JIT (2006) Cardiac autonomic control in patients with refractory epilepsy before and during vagus nerve stimulation treatment: a one-year follow-up study. Epilepsia 47:556–562. doi: 10.1111/j.1528-1167.2006.00467.x CrossRefGoogle Scholar
  76. 76.
    Stemper B, Devinsky O, Haendl T, Welsch G, Hilz MJ (2008) Effects of vagus nerve stimulation on cardiovascular regulation in patients with epilepsy. Acta Neurol Scand 117:231–236. doi: 10.1111/j.1600-0404.2007.00944.x CrossRefGoogle Scholar
  77. 77.
    Zaaimi B, Grebe R, Berquin P, Wallois F (2007) Vagus nerve stimulation therapy induces changes in heart rate of children during sleep. Epilepsia 48:923–930. doi: 10.1111/j.1528-1167.2006.01019.x CrossRefGoogle Scholar
  78. 78.
    Zaaimi B, Grebe R, Berquin P, Wallois F (2009) Vagus nerve stimulation induces changes in respiratory sinus arrhythmia of epileptic children during sleep. Epilepsia 50(11):2473–2480. doi: 10.1111/j.1528-1167.2009.02190.x CrossRefGoogle Scholar
  79. 79.
    Cadeddu C, Deidda M, Mercuro G, Tuveri A, Muroni A, Nocco S, Puligheddu M, Maleci A, Marrosu F (2010) Cardiovascular modulation during vagus nerve stimulation therapy in patients with refractory epilepsy. Epilepsy Res 92:145–152. doi: 10.1016/j.eplepsyres.2010.08.012 CrossRefGoogle Scholar
  80. 80.
    Jansen K, Vandeput S, Milosevic M, Ceulemans B, Van Huffel S, Brown L, Penders J, Lagae L (2011) Autonomic effects of refractory epilepsy on heart rate variability in children: influence of intermittent vagus nerve stimulation. Dev Med Child Neurol 53:1143–1149. doi: 10.1111/j.1469-8749.2011.04103.x CrossRefGoogle Scholar
  81. 81.
    Mulders DM, de Vos CC, Vosman I, van Putten MJ (2015) The effect of vagus nerve stimulation on cardiorespiratory parameters during rest and exercise. Seizure 33:24–28. doi: 10.1016/j.seizure.2015.10.004 CrossRefGoogle Scholar
  82. 82.
    Garamendi I, Acera M, Agundez M, Galbarriatu L, Marinas A, Pomposo I, Valle E, Palma JA, Gomez-Esteban JC (2017) Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy. Seizure 45:56–60. doi: 10.1016/j.seizure.2016.11.018 CrossRefGoogle Scholar
  83. 83.
    Schomer AC, Nearing BD, Schachter SC, Verrier RL (2014) Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy. Epilepsia 55:1996–2002. doi: 10.1111/epi.12855 CrossRefGoogle Scholar
  84. 84.
    Verrier RL, Nearing BD, Olin B, Boon P (2016) Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial. Epilepsy Behav 62:85–89. doi: 10.1016/j.yebeh.2016.06.016 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Iñigo Garamendi-Ruiz
    • 1
    Email author
  • Juan Carlos Gómez-Esteban
    • 2
    • 3
  1. 1.Epilepsy UnitBiocruces Research InstituteBarakaldoSpain
  2. 2.Autonomic and Movement Disorders UnitBiocruces Research InstituteBarakaldoSpain
  3. 3.Department of NeurosciencesUniversity of the Basque CountryLeioaSpain

Personalised recommendations