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Neuromodulation Approaches for Cardiac Arrhythmias: Recent Advances

  • Invasive Electrophysiology and Pacing (EK Heist, Section Editor)
  • Published:
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Abstract

Purpose of Review

This review aims to describe the latest advances in autonomic neuromodulation approaches to treating cardiac arrhythmias, with a focus on ventricular arrhythmias.

Recent Findings

The increasing understanding of neuronal remodeling in cardiac diseases has led to the development and improvement of novel neuromodulation therapies targeting multiple levels of the autonomic nervous system. Thoracic epidural anesthesia, spinal cord stimulation, stellate ganglion modulatory therapies, vagal stimulation, renal denervation, and interventions on the intracardiac nervous system have all been studied in preclinical models, with encouraging preliminary clinical data.

Summary

The autonomic nervous system regulates all the electrical processes of the heart and plays an important role in the pathophysiology of cardiac arrhythmias. Despite recent advances in the clinical application of cardiac neuromodulation, our comprehension of the anatomy and function of the cardiac autonomic nervous system is still limited. Hopefully in the near future, more preclinical data combined with larger clinical trials will lead to further improvements in neuromodulatory treatment for heart rhythm disorders.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Armour JA, Murphy DA, Yuan BX, Mac Donald S, Hopkins DA. Gross and microscopic anatomy of the human intrinsic cardiac nervous system. Anat Rec. 1997;247:289–98.

    Article  CAS  PubMed  Google Scholar 

  2. Vincentz JW, Rubart M, Firulli AB. Ontogeny of cardiac sympathetic innervation and its implications for cardiac disease. Pediatr Cardiol. 2012;33:923–8. https://doi.org/10.1007/s00246-012-0248-1.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ardell JL, Randall WC, Cannon WJ, Schmacht DC, Tasdemiroglu E. Differential sympathetic regulation of automatic, conductile, and contractile tissue in dog heart. Am J Phys. 1988;1988(255):H1050–9. https://doi.org/10.1152/ajpheart.1988.255.5.H1050.

    Article  Google Scholar 

  4. Ajijola OA, Vaseghi M, ZhouW YK, Benharash P, Hadaya J, et al. Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle. Am J Physiol Heart Circ Physiol. 2013;304:H579–88. https://doi.org/10.1152/ajpheart.00754.2012.

    Article  CAS  PubMed  Google Scholar 

  5. Andresen MC, Kuntz DL, Mendelowitz D. In: Armour JA, Ardell JL, editors. Central nervous system regulation of the heart. New York: Oxford University Press; 2004. p. 187–219.

    Google Scholar 

  6. Hopkins DA, Andrew AJ. Ganglionic distribution of afferent neurons innervating the canine heart and cardiopulmonary nerves. J Auton Nerv Syst. 1989;26:213–22.

    Article  CAS  PubMed  Google Scholar 

  7. Armour JA. Potential clinical relevance of the “little brain” on the mammalian heart. Exp Physiol. 2008;93:165–76. https://doi.org/10.1113/expphysiol.2007.041178.

    Article  CAS  PubMed  Google Scholar 

  8. Pauza DH, Skripka V, Pauziene N, Stropus R. Morphology, distribution, and variability of the epicardiac neural ganglionated subplexuses in the human heart. Anat Rec. 2000;259:353–82.

    Article  CAS  PubMed  Google Scholar 

  9. Charpentier F, Drouin E, Gauthier C, LeMarec H. Early after/depolarizations and triggered activity: mechanisms and autonomic regulation. Fundam Clin Pharmacol. 1993;7:39–49.

    Article  CAS  PubMed  Google Scholar 

  10. Zipes DP, Barber MJ, Takahashi N, Gilmour RF Jr. Influence of the autonomic nervous system on the genesis of cardiac arrhythmias. Pacing Clin Electrophysiol. 1983;6:1210–20.

    Article  CAS  PubMed  Google Scholar 

  11. Ajijola OA, Lux RL, Khahera A, Kwon O, Aliotta E, Ennis DB, et al. Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis. Am J Physiol Heart Circ Physiol. 2017;312:H608–21. https://doi.org/10.1152/ajpheart.00575.2016.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Shen MJ, Zipes DP. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res. 2014;114:1004–21. https://doi.org/10.1161/CIRCRESAHA.113.302549.

    Article  CAS  PubMed  Google Scholar 

  13. Yagishita D, Chui RW, Yamakawa K, Rajendran PS, Ajijola OA, Nakamura K, et al. Sympathetic nerve stimulation, not circulating norepinephrine, modulates T-peak to T-end interval by increasing global dispersion of repolarization. Circ Arrhythm Electrophysiol. 2015;8:174–85. https://doi.org/10.1161/CIRCEP.114.002195.

    Article  CAS  PubMed  Google Scholar 

  14. Vanhoutee PM, Verbeuren TJ. Inhibition by acetylcholine of the norepinephrine release evoked by potassium in canine saphenous veins. Circ Res. 1976;39:263–9.

    Article  CAS  PubMed  Google Scholar 

  15. Shanks J, Herring N. Peripheral cardiac sympathetic hyperactivity in cardiovascular disease: role of neuropeptides. Am J Physiol Regul Integr Comp Physiol 2013;305:R1411–20. https://doi.org/10.1152/ajpregu.00118.2013

  16. Calvillo L, Vanoli E, Andreoli E, Besana A, Omodeo E, Gnecchi, et al. Vagal stimulation, through its nicotinic action, limits infarct size and the inflammatory response to myocardial ischemia and reperfusion. J Cardiovasc Pharmacol. 2011;58:500–7. https://doi.org/10.1097/FJC.0b013e31822b7204.

    Article  CAS  PubMed  Google Scholar 

  17. Floras JS. Sympathetic nervous system activation in human heart failure. Clinical implications of an updated model. J Am Coll Cardiol. 2009;54:375–85. https://doi.org/10.1016/j.jacc.2009.03.061.

    Article  CAS  PubMed  Google Scholar 

  18. Schwartz PJ, Pagani M, Lombardi F, Malliani A, Brown AM. A cardio-cardiac sympatho-vagal reflex in the cat. Circ Res. 1973;32:215–20.

    Article  CAS  PubMed  Google Scholar 

  19. Cerati D, Schwartz PJ. Single cardiac vagal fibers activity, acute myocardial ischemia, and risk for sudden death. Circ Res. 1991;69:1389–401.

    Article  CAS  PubMed  Google Scholar 

  20. Zahner MR, Li DP, Chen SR, Pan HL. Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats. J Physiol. 2003;2003(551):515–23. https://doi.org/10.1113/jphysiol.2003.048207.

    Article  CAS  Google Scholar 

  21. Pan HL, Chen SR. Sensing tissue ischemia: another new function for capsaicin receptors? Circulation. 2004;110:1826–31. https://doi.org/10.1161/01.CIR.0000142618.20278.7A.

  22. Uchida Y, Murao S. Bradykinin-induced excitation of afferent cardiac sympathetic nerve fibers. Jpn Heart J. 1974;15:84–91. https://doi.org/10.1536/ihj.15.84.

  23. Schultz HD, Ustinova EE. Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings. Cardiovasc Res. 1998;38:348–55. https://doi.org/10.1016/S0008-6363(98)00031-5.

    Article  CAS  PubMed  Google Scholar 

  24. Wang W, Schultz HD, Ma R. Cardiac sympathetic afferent sensitivity is enhanced in heart failure. Am J Physiol Heart Circ Physiol. 1999;277:H812–7.

    Article  CAS  Google Scholar 

  25. Wang HJ, Wang W, Cornish KG, Rozanski GJ, Zucker IH. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure. Hypertension. 2014;64:745–55. https://doi.org/10.1161/HYPERTENSIONAHA.114.03699.

    Article  CAS  PubMed  Google Scholar 

  26. Cha YM, Redfield MM, Shah S, Shen WK, Fishbein MC, Chen PS. Effects of omapatrilat on cardiac nerve sprouting and structural remodeling in experimental congestive heart failure. Heart Rhythm. 2005;2:984–90. https://doi.org/10.1016/j.hrthm.2005.05.016.

    Article  PubMed  Google Scholar 

  27. Inoue H, Zipes DP. Results of sympathetic denervation in the canine heart: supersensitivity that may be arrhythmogenic. Circulation. 1987;75:877–87.

    Article  CAS  PubMed  Google Scholar 

  28. Inoue H, Zipes DP. Time course of denervation of efferent sympathetic and vagal nerves after occlusion of the coronary artery in the canine heart. Circ Res. 1988;62:1111–20.

    Article  CAS  PubMed  Google Scholar 

  29. Vaseghi M, Lux RL, Mahajan A, Shivkumar K. Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarc- tion. Am J Physiol Heart Circ Physiol. 2012;302:H1838–46. https://doi.org/10.1152/ajpheart.01106.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Verma A, Marrouche NF, Schweikert RA, Saliba W, Wazni O, Cummings J, et al. Relationship between successful ablation sites and the scar border zone defined by substrate mapping for ventricular tachycardia post-myocardial infarction. J Cardiovasc Electrophysiol. 2005;16:465–71. https://doi.org/10.1046/j.1540-8167.2005.40443.x.

    Article  PubMed  Google Scholar 

  31. • Klein T, Abdulghani M, Smith M, Huang R, Asoglu R, Remo BF, et al. Three-Dimensional 123I-Meta-Iodobenzylguanidine Cardiac Innervation Maps to Assess Substrate and Successful Ablation Sites for Ventricular Tachycardia: Feasibility Study for a Novel Paradigm of Innervation Imaging. Circ Arrhythm Electrophysiol. 2015;8:583–91. https://doi.org/10.1161/CIRCEP.114.002105. First in humans study who demonstrated the possibility of using 123I-Meta-Iodobenzylguanidine to build three-dimensional innervation maps of the heart to guide VT ablation procedures.

    Article  PubMed  Google Scholar 

  32. Han S, Kobayashi K, Joung B, Piccirillo G, Maruyama M, Vinters HV, et al. Electroanatomic remodeling of the left stellate ganglion after myocardial infarction. J Am Coll Cardiol. 2012;59:954–61. https://doi.org/10.1016/j.jacc.2011.11.030.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ajijola OA, Yagishita D, Reddy NK, Yamakawa K, Vaseghi M, Downs AM, et al. Remodeling of stellate ganglion neurons after spatially targeted myocardial infarction: neuropeptide and morphologic changes. Heart Rhythm. 2015;12:1027–35. https://doi.org/10.1016/j.hrthm.2015.01.045.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ajijola OA, Wisco JJ, Lambert HW, Mahajan A, Stark E, Fishbein MC, et al. Extracardiac neural remodeling in humans with cardiomyopathy. Circ Arrhythm Electrophysiol. 2012;5:1010–116. https://doi.org/10.1161/CIRCEP.112.972836.

    Article  PubMed  PubMed Central  Google Scholar 

  35. • Ajijola OA, Hoover DB, Simerly TM, Brown TC, Yanagawa J, Biniwale RM, et al. Inflammation, oxidative stress, and glial cell activation characterize stellate ganglia from humans with electrical storm. JCI Insight. 2017;2:e94715. https://doi.org/10.1172/jci.insight.94715. Detailed in vitro evaluation of the stellate ganglia from humans with structural heart disease and electrical storm showing neuronal remodeling.

    Article  PubMed Central  Google Scholar 

  36. Xiao L, Haack KK, Zucker IH. Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 signaling. Am J Phys Cell Phys. 2013;304:C1073–9. https://doi.org/10.1152/ajpcell.00364.2012.

    Article  CAS  Google Scholar 

  37. Zucker IH, Gao L. The regulation of sympathetic nerve activity by angiotensin II involves reactive oxygen species and MAPK. Circ Res. 2005;97:737–9. https://doi.org/10.1161/01.RES.0000188261.94569.1f.

    Article  CAS  PubMed  Google Scholar 

  38. Lambert GW, Kaye DM, Lefkovits J, Jennings GL, Turner AG, Cox HS, et al. Increased central nervous system monoamine neurotransmitter turnover and its association with sympathetic nervous activity in treated heart failure patients. Circulation. 1995;92:1813–8.

    Article  CAS  PubMed  Google Scholar 

  39. Rizzo S, Basso C, Troost D, Aronica E, Frigo AC, Driessen AH, et al. T-cell-mediated inflammatory activity in the stellate ganglia of patients with ion-channel disease and severe ventricular arrhythmias. Circ Arrhythm Electrophysiol. 2014;7:224–9. https://doi.org/10.1161/CIRCEP.113.001184.

    Article  CAS  PubMed  Google Scholar 

  40. Nador F, Beria G, De Ferrari GM, Stramba-Badiale M, Locati EH, Lotto A, et al. Unsuspected echocardiographic abnormality in the long QT syndrome: diagnostic, prognostic, and pathogenetic implications. Circulation. 1991;84:1530–42.

    Article  CAS  PubMed  Google Scholar 

  41. Haugaa KH, Amlie JP, Berge KE, Leren TP, Smiseth OA, Edvardsen T. Transmural differences in myocardial contraction in long-QT syndrome: mechanical consequences of ion channel dysfunction. Circulation. 2010;122:1355–63. https://doi.org/10.1161/CIRCULATIONAHA.110.960377.

    Article  PubMed  Google Scholar 

  42. Leren IS, Hasselberg NE, Saberniak J, Håland TF, Kongsgård E, Smiseth OA, et al. Cardiac mechanical alterations and genotype specific differences in subjects with long QT syndrome. J Am Coll Cardiol Img. 2015;8:501–10. https://doi.org/10.1016/j.jcmg.2014.12.023.

    Article  Google Scholar 

  43. Haugaa KH, Edvardsen T, Leren TP, Gran JM, Smiseth OA, Amlie JP. Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome. Eur Heart J. 2009;30:330–7. https://doi.org/10.1093/eurheartj/ehn466.

    Article  PubMed  Google Scholar 

  44. Hamon D, Rajendran PS, Chui RW, Ajijola OA, Irie T, Talebi R, et al. Premature ventricular contraction coupling interval variability destabilizes cardiac neuronal and electrophysiological control: insights from simultaneous cardioneural mapping. Circ Arrhythm Electrophysiol. 2017;10. https://doi.org/10.1161/CIRCEP.116.004937.

  45. Tung R, Shivkumar K. Neuraxial modulation for treatment of VT storm. J Biomed Res. 2015;29:56–60. https://doi.org/10.7555/JBR.29.20140161.

    Article  PubMed  Google Scholar 

  46. Howard-Quijano K, Takamiya T, Dale EA, Kipke J, Kubo Y, Grogan T, et al. Spinal cord stimulation reduces ventricular arrhythmias during acute ischemia by attenuation of regional myocardial excitability. Am J Physiol Heart Circ Physiol. 2017;313:H421–31. https://doi.org/10.1152/ajpheart.00129.2017.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Bourke T, Vaseghi M, Michowitz Y, Sankhla V, Shah M, Swapna N, et al. Neuraxial modulation for refractory ventricular arrhythmias: value of thoracic epidural anesthesia and surgical left cardiac sympathetic denervation. Circulation. 2010;121:2255–62. https://doi.org/10.1161/CIRCULATIONAHA.109.929703.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, et al. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J. 2002;23:355–70.

    Article  CAS  PubMed  Google Scholar 

  49. Zhang TC, Janik JJ, Grill WM. Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain. Brain Res. 2014;1569:19–31. https://doi.org/10.1016/j.brainres.2014.04.039.

    Article  CAS  PubMed  Google Scholar 

  50. Wang S, Zhou X, Huang B, Wang Z, Liao K, Saren G, et al. Spinal cord stimulation protects against ventricular arrhythmias by suppressing left stellate ganglion neural activity in an acute myocardial infarction canine model. Heart Rhythm. 2015;12:1628–35. https://doi.org/10.1016/j.hrthm.2015.03.023.

    Article  PubMed  Google Scholar 

  51. Odenstedt J, Linderoth B, Bergfeldt L, Ekre O, Grip L, Mannheimer C, et al. Spinal cord stimulation effects on myocardial ischemia, infarct size, ventricular arrhythmia, and noninvasive electrophysiology in a porcine ischemia–reperfusion model. Heart Rhythm. 2011;8:892–8. https://doi.org/10.1016/j.hrthm.2011.01.029.

    Article  PubMed  Google Scholar 

  52. Grimaldi R, de Luca A, Kornet L, Castagno D, Gaita F. Can spinal cord stimulation reduce ventricular arrhythmias? Heart Rhythm. 2012;9:1884–7. https://doi.org/10.1016/j.hrthm.2012.08.007.

    Article  PubMed  Google Scholar 

  53. Tse HF, Turner S, Sanders P, Okuyama Y, Fujiu K, Cheung CW, et al. Thoracic Spinal Cord Stimulation for Heart Failure as a Restorative Treatment (SCS HEART study): first-in-man experience. Heart Rhythm. 2015;12:588–95. https://doi.org/10.1111/j.1540-8167.2011.02230.x.

    Article  PubMed  Google Scholar 

  54. Zipes DP, Neuzil P, Theres H, Caraway D, Mann DL, Mannheimer C, et al. Determining the feasibility of spinal cord neuromodulation for the treatment of chronic systolic heart failure: the DEFEAT-HF study. JACC Heart Fail. 2016;4:129–36. https://doi.org/10.1016/j.jchf.2015.10.006.

    Article  PubMed  Google Scholar 

  55. Schwartz PJ, Stone HL, Brown AM. Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion. Am. Heart J. 1976;92:589–99.

    CAS  Google Scholar 

  56. Schwartz PJ, Billman GE, Stone HL. Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction: an experimental preparation for sudden cardiac death. Circulation. 1984;69:790–800.

    Article  CAS  PubMed  Google Scholar 

  57. • Irie T, Yamakawa K, Hamon D, Nakamura K, Shivkumar K, Vaseghi M. Cardiac sympathetic innervation via middle cervical and stellate ganglia and antiarrhythmic mechanism of bilateral stellectomy. Am J Physiol Heart Circ Physiol. 2017;312:H392–405. https://doi.org/10.1152/ajpheart.00644.2016. First demonstration in a big animal model of the rule of middle cervical ganglia in regulating electrical properties of the heart and cardiovascular reflexes.

    Article  PubMed  Google Scholar 

  58. Schwartz PJ, Snebold NG, Brown AM. Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold. Am J Cardiol. 1976;37:1034–40.

    Article  CAS  PubMed  Google Scholar 

  59. Schwartz PJ, Malliani A. Electrical alternation of the T wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long QT syndrome. Am. Heart J. 1975;89:45–50.

    CAS  Google Scholar 

  60. Cao JM, Chen LS, KenKnight BH, Ohara T, Lee MH, Tsai J, et al. Nerve sprouting and sudden cardiac death. Circ Res. 2000;86:816–21.

    Article  CAS  PubMed  Google Scholar 

  61. Schwartz PJ, De Ferrari GM, Pugliese L. Cardiac sympathetic denervation 100 years later: Jonnesco would have never believed it. Int J Cardiol. 2017;237:25–8. https://doi.org/10.1016/j.ijcard.2017.03.020.

    Article  PubMed  Google Scholar 

  62. Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation. 2004;109:1826–33. https://doi.org/10.1161/01.CIR.0000125523.14403.1E.

    Article  PubMed  Google Scholar 

  63. •• De Ferrari GM, Dusi V, Spazzolini C, Bos JM, Abrams DJ, Berul CI, et al. Clinical management of catecholaminergic polymorphic ventricular tachycardia: the role of left cardiac sympathetic denervation. Circulation. 2015;131:2185–93. https://doi.org/10.1161/CIRCULATIONAHA.115.015731. The largest human study showing the efficacy of LCSD in VAs in CVPT.

    Article  PubMed  Google Scholar 

  64. Odero A, Bozzani A, De Ferrari GM, Schwartz PJ. Left cardiac sympathetic denervation for the prevention of life-threatening arrhythmias: the surgical supraclavicular approach to cervicothoracic sympathectomy. Heart Rhythm. 2010;7:1161–5. https://doi.org/10.1016/j.hrthm.2010.03.046.

    Article  PubMed  Google Scholar 

  65. Collura CA, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. Heart Rhythm. 2009;6:752–9. https://doi.org/10.1016/j.hrthm.2009.03.024.

    Article  PubMed  Google Scholar 

  66. Kwon OJ, Pendekanti S, Fox JN, Yanagawa J, Fishbein MC, Shivkumar K, et al. Morphological spectra of adult human stellate ganglia: implications for thoracic sympathetic denervation. Anat Rec. 2018. https://doi.org/10.1002/ar.23797.

  67. Zaidi ZF, Ashraf A. The nerve of Kunz: incidence, location and variations. J Appl Sci Res. 2010;6:659–64.

    Google Scholar 

  68. Waddell-Smith KE, Ertresvaag KN, Li J, Chaudhuri K, Crawford JR, Hamill JK, et al. Physical and psychological consequences of left cardiac sympathetic denervation in long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2015;8:1151–8. https://doi.org/10.1161/CIRCEP.115.003159.

    Article  CAS  PubMed  Google Scholar 

  69. Coleman MA, Bos MJ, Johnson JN, Owen HJ, Deschamps C, Moir C, et al. Videoscopic left cardiac sympathetic denervation for patients with recurrent ventricular fibrillation/malignant ventricular arrhythmia syndromes besides congenital long-QT syndrome. Circ Arrhythm Electrophysiol. 2012;5:782–8. https://doi.org/10.1161/CIRCEP.112.971754.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Ajijola OA, Lellouche N, Bourke T, Tung R, Ahn S, Mahajan A, et al. Bilateral cardiac sympathetic denervation for the management of electrical storm. J Am Coll Cardiol. 2012;59:91–2. https://doi.org/10.1016/j.jacc.2011.09.043.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Vaseghi M, Gima J, Kanaan C, Ajijola OA, Marmureanu A, Mahajan A, et al. Cardiac sympathetic denervation in patients with refractory ven- tricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm. 2014;11:360–6. https://doi.org/10.1016/j.hrthm.2013.11.028.

    Article  PubMed  Google Scholar 

  72. •• Vaseghi M, Barwad P, Malavassi Corrales FJ, Tandri H, Mathuria N, et al. Cardiac sympathetic denervation for refractory ventricular arrhythmias. J Am Coll Cardiol. 2017;69:3070–80. https://doi.org/10.1016/j.jacc.2017.04.035. The largest and most recent study showing that CSD decreased VAs in patients with structural heart disease.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Romero J, Di Biase L, Diaz JC, Quispe R, Du X, Briceno D, et al. Early versus late referral for catheter ablation of ventricular tachycardia in patients with structural heart disease. JACC. 2018;3:374–82. https://doi.org/10.1016/j.jacep.2017.12.008.

    Article  Google Scholar 

  74. Leriche R, Fontaine R. L’Anesthe ́ sie isole ́ e du ganglion e ́ toile ́ . Sa technique, ses indications, ses re ́ sultats. Presse Med. 1934;42:849–50.

    Google Scholar 

  75. Gofeld M, Bhatia A, Abbas S, Ganapathy S, Johnson M. Development and validation of a new technique for ultrasound-guided stellate ganglion block. Reg Anesth Pain Med. 2009;34:475–9. https://doi.org/10.1097/AAP.0b013e3181b494de.

    Article  PubMed  Google Scholar 

  76. Hayase J, Vampola S, Ahadian F, Narayan SM, Krummen DE. Comparative efficacy of stellate ganglion block with bupivacaine vs pulsed radiofrequency in a patient with refractory ventricular arrhythmias. J Clin Anesth. 2016;31:162–5. https://doi.org/10.1016/j.jclinane.2016.01.026.

    Article  PubMed  Google Scholar 

  77. Meng L, Tseng CH, Shivkumar K, Ajijola O. Efficacy of stellate ganglion blockade in managing electrical storm: a systematic review. JACC Clin Electrophysiol. 2017;9:942–9. https://doi.org/10.1016/j.jacep.2017.06.006.

    Article  Google Scholar 

  78. Kumar R, Woo MA, Birrer BV, Macey PM, Fonarow GC, Hamilton MA, et al. Mammillary bodies and fornix fibers are injured in heart failure. Neurobiol Dis. 2009;33:236–42. https://doi.org/10.1016/j.nbd.2008.10.004.

    Article  PubMed  Google Scholar 

  79. Woo MA, Palomares JA, Macey PM, Fonarow GC, Harper RM, Kumar R. Global and regional brain mean diffusivity changes in patients with heart failure. J Neurosci Res. 2015;93:678–85. https://doi.org/10.1002/jnr.23525.

    Article  CAS  PubMed  Google Scholar 

  80. Zuanetti G, De Ferrari GM, Priori SG, Schwartz PJ. Protective effect of vagal stimulation on reperfusion arrhythmias in cats. Circ Res. 1987;61:429–35.

    Article  CAS  PubMed  Google Scholar 

  81. Vanoli E, De Ferrari GM, Stramba-Badiale M, Hull SS Jr, Foreman RD, Schwartz PJ. Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction. Circ Res. 1991;68:1471–81.

    Article  CAS  PubMed  Google Scholar 

  82. Nazeri A, Elayda MA, Dragnev L, Frank CM, Qu J, Afonso VX, et al. Heterogeneity of left ventricular signal characteristics in response to acute vagal stimulation during ventricular fibrillation in dogs. Tex Heart Inst J. 2011;38:621–6.

    PubMed  PubMed Central  Google Scholar 

  83. Ardell JL, Rajendran PS, Nier HA, KenKnight BH, Armour JA. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function. Am J Physiol Heart Circ Physiol. 2015;309:H1740–52. https://doi.org/10.1152/ajpheart.00557.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Yoo PB, Lubock NB, Hincapie JG, Ruble SB, Hamann JJ, Grill WM. High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog. J Neural Eng. 2013;10:026003. https://doi.org/10.1088/1741-2560/10/2/026003.

    Article  PubMed  Google Scholar 

  85. • Yamaguchi N, Yamakawa K, Rajendran PS, Takamiya T, Vaseghi M. Antiarrhythmic effects of vagal nerve stimulation after cardiac sympathetic denervation in the setting of chronic myocardial infarction. Heart Rhythm. 2018;15:1214–22. https://doi.org/10.1016/j.hrthm.2018.03.012. First animal study showing the beneficial antiarrhythmic effects of VNS after CSD in the setting of chronic myocardial infarction.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Uthman BM, Reichl AM, Dean JC, Eisenschenk S, Gilmore R, Reid S, et al. Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year observation. Neurology. 2004;63:1124–6.

    Article  CAS  PubMed  Google Scholar 

  87. Shuchman M. Approving the vagus-nerve stimulator for depression. N Engl J Med. 2007;356:1604–7. https://doi.org/10.1056/NEJMp078035.

    Article  CAS  PubMed  Google Scholar 

  88. •• 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;594:3911–54. https://doi.org/10.1113/JP271870. First position paper by international experts in the field defining the rationale and the clinical impact of neuroscience-based cardiovascular therapeutics.

  89. Yu L, Wang S, Zhou X, Wang Z, Huang B, Liao K, et al. Chronic intermittent low-level stimulation of tragus reduces cardiac autonomic remodeling and ventricular arrhythmia inducibility in a post-infarction canine model. JACC Clin Electrophysiol. 2016;2:330–9. https://doi.org/10.1016/j.jacep.2015.11.006.

    Article  PubMed  Google Scholar 

  90. • Yu L, Huang B, Po SS, Tan T, Wang M, Zhou L, et al. Low-Level tragus stimulation for the treatment of ischemia and reperfusion injury in patients with ST-segment elevation myocardial infarction: a proof-of-concept study. JACC Cardiovasc Interv. 2017;10:1511–20. https://doi.org/10.1016/j.jcin.2017.04.036. First in humans, randomized study showing the beneficial effect of low-level tragus stimulation for the treatment of ischemia and reperfusion injury.

    Article  PubMed  Google Scholar 

  91. 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;123:2204–12. https://doi.org/10.1161/CIRCULATIONAHA.111.018028.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Katritsis DG, Pokushalov E, Romanov A, Giazitzoglou E, Siontis GC, Po SS, et al. Autonomic denervation added to pulmonary vein isolation for paroxysmal atrial fibrillation: a randomized clinical trial. JAmColl Cardiol. 2013;62:2318–25. https://doi.org/10.1016/j.jacc.2013.06.053.

    Article  Google Scholar 

  93. • Driessen AH, Berger WR, Krul SP, Vanden Berg NW, Neefs J, Piersma FR, et al. Ganglion plexus ablation in advanced atrial fibrillation: the AFACT study. J Am Coll Cardiol. 2016;68:1155–65. https://doi.org/10.1016/j.jacc.2016.06.036 .The largest, randomized clinical trial of ganglion plexus ablation in advanced atrial fibrillation, with negative finding.

  94. Pokushalov E, Kozlov B, Romanov A, Strelnikov A, Bayramova S, Sergeevichev D, et al. Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pad in patients undergoing cardiac surgery: one-year follow-up of a randomized pilot study. Circ Arrhythm Electrophysiol. 2015;8:1334–41. https://doi.org/10.1161/CIRCEP.115.003199.

    Article  CAS  PubMed  Google Scholar 

  95. Lo LW, Scherlag BJ, Chang HY, Lin YJ, Chen SA, Po SS. Paradoxical long-term proarrhythmic effects after ablating the “head station” ganglionated plexi of the vagal innervation to the heart. Heart Rhythm. 2013;10:751–7. https://doi.org/10.1016/j.hrthm.2013.01.030.

    Article  PubMed  Google Scholar 

  96. He B, Lu Z, He W, Wu L, Cui B, Hu X, et al. Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia. Int J Cardiol. 2013;168:86–93. https://doi.org/10.1016/j.ijcard.2012.09.067.

    Article  PubMed  Google Scholar 

  97. Vaseghi M, Lellouche N, Ritter H, Fonarow GC, Patel JK, Moriguchi J, et al. Mode and mechanisms of death after orthotopic heart transplantation. Heart Rhythm. 2009;6:503–9. https://doi.org/10.1016/j.hrthm.2009.01.005.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Vaseghi M, Boyle NG, Kedia R, Patel JK, Cesario DA, Wiener I, et al. Supraventricular tachycardia after orthotopic cardiac transplantation. J Am Coll Cardiol. 2008;51:2241–9. https://doi.org/10.1016/j.jacc.2008.02.065.

    Article  PubMed  Google Scholar 

  99. Jackson N, Gizurarson S, Azam MA, King B, Ramadeen A, Zamiri N, et al. Effects of renal artery denervation on ventricular arrhythmias in a postinfarct model. Circ Cardiovasc Interv. 2017;10:e004172. https://doi.org/10.1161/CIRCINTERVENTIONS.116.004172.

    Article  CAS  PubMed  Google Scholar 

  100. Armaganijan LV, Staico R, Moreira DA, Lopes RD, Medeiros PT, Habib R, et al. 6-month outcomes in patients with implantable cardioverter-defibrillators undergoing renal sympathetic denervation for the treatment of refractory ventricular arrhythmias. JACC Cardiovasc Interv. 2015;8:984–90. https://doi.org/10.1016/j.jcin.2015.03.012.

    Article  PubMed  Google Scholar 

  101. Evranos B, Canpolat U, Kocyigit D, Coteli C, Yorgun H, Aytemir K, et al. Role of adjuvant renal sympathetic denervation in the treatment of ventricular arrhythmias. Am J Cardiol. 2016;118:1207–10. https://doi.org/10.1016/j.amjcard.2016.07.036.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Medicine, Section of Cardiology; Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo., University of Pavia, Pavia, Italy

    Veronica Dusi

  2. UCLA Cardiac Arrhythmia Center, UCLA Neurocardiology Research Center, David Geffen School of Medicine at UCLA, University of California, 100 Medical Plaza, Suite 660, Westwood Blvd, Los Angeles, CA, 90095-1679, USA

    Veronica Dusi, Ching Zhu & Olujimi A. Ajijola

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Veronica Dusi, Ching Zhu, and Olujimi A. Ajijola declare that they have no conflict of interest.

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This is a review article so we have referenced studies done in humans and animals, but these studies were not done as part of this article, and they are just referenced here. For those studies, 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. And all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Dusi, V., Zhu, C. & Ajijola, O.A. Neuromodulation Approaches for Cardiac Arrhythmias: Recent Advances. Curr Cardiol Rep 21, 32 (2019). https://doi.org/10.1007/s11886-019-1120-1

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