Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cardiac sympathetic denervation to prevent life-threatening arrhythmias

Nature Reviews Cardiology volume 11, pages 346–353 (2014)Cite this article

Subjects

Key Points

  • After initial reports of the successful treatment of patients with angina, left cardiac sympathetic denervation (LCSD) entered clinical practice in the 1970s for patients with long QT syndrome (LQTS)

  • LCSD prevents arrhythmias of ischaemic origin, raises the threshold for ventricular fibrillation (VF), does not induce postdenervation supersensitivity, improves the capacity of coronary arteries to dilate, and preserves cardiac contractility

  • The different effects of LCSD versus right cardiac sympathetic denervation are explained by the fact that the left-sided cardiac sympathetic nerves are quantitatively dominant at the ventricular level

  • LCSD has proved to be highly effective in preventing life-threatening cardiac arrhythmias in patients with LQTS, catecholaminergic polymorphic ventricular tachycardia, or those at high cardiovascular risk after myocardial infarction

  • Preliminary data, and important effects on VF threshold, suggest that LCSD might be useful in many conditions characterized by high risk of life-threatening arrhythmias, including ischaemic, dilated, and hypertrophic cardiomyopathy

  • Cardiologists should discuss the advantages and disadvantages of LCSD compared with those of an implantable cardioverter–defibrillator with all patients, particularly children, who are at risk of arrhythmic sudden death

Abstract

Experimental and clinical evidence indicating an antiarrhythmic effect of cardiac sympathetic denervation has been available for 100 years. Experimental data show that left cardiac sympathetic denervation (LCSD), in particular, is not only antiarrhythmic, but also antifibrillatory—an effect exquisitely important for any clinical condition associated with a high risk of ventricular fibrillation and sudden cardiac death. LCSD has additional effects on both the coronary circulation and the mechanical performance of the left ventricle, with important implications for patients with ischaemic cardiomyopathy. Evidence also shows that LCSD increases the vagal activity directed to the heart, which has potential implications for the management of heart failure. In this Review, the current and novel clinical indications for LCSD are discussed, particularly in the context of results obtained in patients with channelopathies, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cardiac innervation and left sympathetic cardiac denervation.
Figure 2: Left stellate ganglion blockade is antiarrhythmic.
Figure 3: Effect of unilateral stellectomy and blockade on ventricular fibrillation threshold.
Figure 4: Left stellectomy is accompanied by a reflex increase in cardiac vagal efferent nerve activity.
Figure 5: LCSD reduces the incidence of sudden cardiac death after myocardial infarction.

Similar content being viewed by others

References

  1. Lown, B. Sudden cardiac death: the major challenge confronting contemporary cardiology. Am. J. Cardiol. 43, 313–320 (1979).

    Article  CAS  PubMed  Google Scholar 

  2. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. The Sicilian Gambit: a new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Eur. Heart J. 12, 1112–1131 (1991).

  3. Leriche, R., Herman, L. & Fontaine, R. Ligature de la coronaire gauche et fonction du cœur après énervation sympathique [French]. C. R. Soc. Biol. 107, 547–548 (1931).

    Google Scholar 

  4. Cox, W. V., Lewiston, M. E. & Robertson, H. F. The effect of stellate ganglionectomy on the cardiac function of intact dogs: and its effect on the extent of myocardial infarction and on cardiac function following coronary artery occlusion. Am. Heart J. 12, 285–300 (1936).

    Article  Google Scholar 

  5. Schauer, G., Gross, L. & Blum, L. Hemodynamic studies in experimental coronary occlusion: IV. Stellate ganglionectomy experiments. Am. Heart J. 14, 669–676 (1937).

    Article  Google Scholar 

  6. McEachern, C. G., Manning, G. W. & Hall, G. E. Sudden occlusion of coronary arteries following removal of cardiosensory pathways: an experimental study. Arch. Intern. Med. 65, 661–670 (1940).

    Article  Google Scholar 

  7. Harris, A. S., Estandia, A. & Tillotson, R. F. Ventricular ectopic rhythms and ventricular fibrillation following cardiac sympathectomy and coronary occlusion. Am. J. Physiol. 165, 505–512 (1951).

    Article  CAS  PubMed  Google Scholar 

  8. Milch, E. et al. Experimental prevention of sudden death from acute coronary artery occlusion in the dog. Am. Heart J. 50, 483–491 (1955).

    Article  CAS  PubMed  Google Scholar 

  9. Skelton, R. B., Gergely, N., Manning, G. W. & Coles, J. C. Mortality studies in experimental coronary occlusion. J. Thorac. Cardiovasc. Surg. 44, 90–96 (1962).

    CAS  PubMed  Google Scholar 

  10. Schaal, S. F., Wallace, A. G. & Sealy, W. C. Protective influence of cardiac denervation against arrhythmias of myocardial infarction. Cardiovasc. Res. 3, 241–244 (1969).

    Article  CAS  PubMed  Google Scholar 

  11. Ebert, P. A., Vanderbeek, R. B., Allgood, R. J. & Sabiston, D. C. Jr. Effect of chronic cardiac denervation on arrhythmias after coronary artery ligation. Cardiovasc. Res. 4, 141–147 (1970).

    Article  CAS  PubMed  Google Scholar 

  12. Fowlis, R. A. F., Sang, C. T. M., Lundy, P. M., Ahuja, S. P. & Colhoun, H. Experimental coronary artery ligation in conscious dogs six months after bilateral cardiac sympathectomy. Am. Heart J. 88, 748–757 (1974).

    Article  CAS  PubMed  Google Scholar 

  13. Schwartz, P. J. & Stone, H. L. Left stellectomy in the prevention of ventricular fibrillation caused by acute myocardial ischemia in conscious dogs with anterior myocardial infarction. Circulation 62, 1256–1265 (1980).

    Article  CAS  PubMed  Google Scholar 

  14. Schwartz, P. J. Cutting nerves and saving lives. Heart Rhythm 6, 760–763 (2009).

    Article  PubMed  Google Scholar 

  15. Francois-Frank, C. A. Signification physiologique de la resection du sympathique dans la maladie de Basedow, l'epilepsie, l'idiotic et le glaucoma [French]. Bull. Acad. Méd. Paris 41, 565–594 (1899).

    Google Scholar 

  16. Jonnesco, T. Traitement chirurgical de l'angine de poitrine par la résection du sympathique cervico-thoracique [French]. Presse Méd. 20, 221–230 (1921).

    Google Scholar 

  17. Danielopolu, D. Le traitement chirurgical de l'angine de poitrine à la lumière des dernières recherches cliniques et expérimentales [French]. C. R. Soc. Bio. Tome I 92, 1157 (1925).

    Google Scholar 

  18. Reid, M. R. & Dewitt Andrus, W. The surgical treatment of angina pectoris. Ann. Surg. 81, 591–604 (1925).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Leriche, R. & Fontaine, R. Rôle du ganglion étoile gauche dans le déterminisme de la crise de l'angine de poitrine [French]. C. R. Acad. Sci. 188, 279–280 (1929).

    Google Scholar 

  20. Danielopolu, D. L'infarctus du myocarde accident de la stellectomie dans l'angine de poitrine [French]. Presse Méd. 56, 337–338 (1948).

    Google Scholar 

  21. Lindgren, I. & Olivecrona, H. Surgical treatment of angina pectoris. J. Neurosurg. 4, 19–39 (1947).

    Article  CAS  PubMed  Google Scholar 

  22. Burnett, C. F. & Evans, J. A. Follow-up report on resection of the anginal pathway in thirty-three patients. JAMA 162, 709–712 (1956).

    Article  Google Scholar 

  23. Cox, W. V. Influence of stellate ganglion block on angina pectoris and the post-exercise ECG. Am. J. Med. 252, 289–295 (1966).

    Article  Google Scholar 

  24. Estes, E. H. Jr & Izlar, H. R. Jr. Recurrent ventricular tachycardia: a case successfully treated by bilateral cardiac sympathectomy. Am. J. Med. 31, 493–497 (1961).

    Article  PubMed  Google Scholar 

  25. Zipes, D. P. et al. Treatment of ventricular arrhythmia by permanent atrial pacemaker and cardiac sympathectomy. Ann. Intern. Med. 68, 591–597 (1968).

    Article  CAS  PubMed  Google Scholar 

  26. Moss, A. J. & McDonald, J. Unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome. N. Engl. J. Med. 285, 903–904 (1971).

    Article  CAS  PubMed  Google Scholar 

  27. Yanowitz, F., Preston, J. B. & Abildskov, J. A. Functional distribution of right and left stellate innervation to the ventricles: production of neurogenic electrocardiographic changes by unilateral alteration of sympathetic tone. Circ. Res. 18, 416–428 (1966).

    Article  CAS  PubMed  Google Scholar 

  28. Schwartz, P. J., Periti, M. & Malliani, A. The long QT syndrome. Am. Heart J. 89, 378–390 (1975).

    Article  CAS  PubMed  Google Scholar 

  29. Schwartz, P. J. & 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. 89, 45–50 (1975).

    Article  CAS  PubMed  Google Scholar 

  30. Schwartz, P. J. Idiopathic long QT syndrome: progress and questions. Am. Heart J. 109, 399–411 (1985).

    Article  CAS  PubMed  Google Scholar 

  31. Schwartz, P. J. The rationale and the role of left stellectomy for the prevention of malignant arrhythmias. Ann. N.Y. Acad. Sci. 427, 199–221 (1984).

    Article  CAS  PubMed  Google Scholar 

  32. Schwartz, P. J. in Nervous Control of Cardiovascular Function Ch. 10 (ed. Randall, W. C.) 225–252 (Oxford University Press, 1984).

    Google Scholar 

  33. Schwartz, P. J. & Priori, S. G. in Cardiac Electrophysiology: From Cell to Bedside 1st edn Ch. 37 (eds Zipes, D. P. & Jalife, J.) 330–343 (Saunders, 1990).

    Google Scholar 

  34. Schwartz, P. J., Stone, H. L. & Brown, A. M. Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion. Am. Heart J. 92, 589–599 (1976).

    Article  CAS  PubMed  Google Scholar 

  35. Schwartz, P. J., Billman, G. E. & Stone. H. L. 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 69, 790–800 (1984).

    Article  CAS  PubMed  Google Scholar 

  36. Schwartz, P. J., Snebold, N. G. & Brown, A. M. Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold. Am. J. Cardiol. 37, 1034–1040 (1976).

    Article  CAS  PubMed  Google Scholar 

  37. Odero, A., Bozzani, A., De Ferrari, G. M. & Schwartz, P. J. Left cardiac sympathetic denervation for the prevention of life-threatening arrhythmias. the surgical supraclavicular approach to cervico-thoracic sympathectomy. Heart Rhythm 7, 1161–1165 (2010).

    Article  PubMed  Google Scholar 

  38. Harris, A. S., Otero, H. & Bocage, A. J. The induction of arrhythmias by sympathetic activity before and after occlusion of a coronary artery in the canine heart. J. Electrocardiol. 4, 34–43 (1971).

    Article  CAS  PubMed  Google Scholar 

  39. Schwartz, P. J. & Vanoli, E. Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs. J. Cardiovasc. Pharmacol. 3, 1251–1259 (1981).

    Article  CAS  PubMed  Google Scholar 

  40. Schwartz, P. J., Vanoli, E., Zaza, A. & Zuanetti, G. The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity. Am. Heart J. 109, 937–948 (1985).

    Article  CAS  PubMed  Google Scholar 

  41. Schwartz, P. J. & Stone, H. L. Effects of unilateral stellectomy upon cardiac performance during exercise in dogs. Circ. Res. 44, 637–645 (1979).

    Article  CAS  PubMed  Google Scholar 

  42. Cannon, W. B. A law of denervation. Am. J. Med. Sci. 198, 737–750 (1939).

    Article  Google Scholar 

  43. Goodall, M. & Kirshner, N. Effect of cervico-thoracic ganglionectomy on the adrenaline and noradrenaline content in the mammalian heart. J. Clin. lnvest. 35, 649–656 (1956).

    Article  CAS  Google Scholar 

  44. Hertting, G. & Schlefthaler, T. H. The effect of stellate ganglion excision on the catecholamine content and the uptake of 3H-norepinephrine in the heart of the cat. lnt. J. Neuropharmacol. 3, 65–69 (1964).

    Article  CAS  Google Scholar 

  45. Schwartz, P. J. & Stone, H. L. Left stellectomy and denervation supersensitivity in conscious dogs. Am. J. Cardiol. 49, 1185–1190 (1982).

    Article  CAS  PubMed  Google Scholar 

  46. Randall, W. C. & Rohse, W. G. The augmentor action of the sympathetic cardiac nerves. Circ. Res. 4, 470–475 (1956).

    Article  CAS  PubMed  Google Scholar 

  47. Schwartz, P. J., Verrier, R. L. & Lown, B. Effect of stellectomy and vagotomy on ventricular refractoriness. Circ. Res. 40, 536–540 (1977).

    Article  CAS  PubMed  Google Scholar 

  48. Cerati, D. & Schwartz, P. J. Single cardiac vagal fibers activity, acute myocardial ischemia, and risk for sudden death. Circ. Res. 69, 1389–1401 (1991).

    Article  CAS  PubMed  Google Scholar 

  49. Malliani, A., Recordati, G. & Schwartz, P. J. Nervous activity of afferent cardiac sympathetic fibres with atrial and ventricular endings. J. Physiol. 229, 457–469 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schwartz, P. J., Pagani, M., Lombardi, F., Malliani, A. & Brown, A. M. A cardio-cardiac sympatho-vagal reflex in the cat. Circ. Res. 32, 215–220 (1973).

    Article  CAS  PubMed  Google Scholar 

  51. Schwartz, P. J. Autonomic modulation for chronic heart failure: a new kid on the block? Eur. J. Heart Fail. 14, 1316–1318 (2012).

    Article  PubMed  Google Scholar 

  52. De Ferrari, G. M. & Schwartz, P. J. Left cardiac sympathetic denervation in patients with heart failure: a new indication for an old intervention? J. Cardiovasc. Trans. Res. http://dx.doi.org/10.1007/s12265-014-9541-0.

  53. Schwartz, P. J. et al. Long term vagal stimulation in patients with advanced heart failure: first experience in man. Eur. J. Heart Fail. 10, 884–891 (2008).

    Article  PubMed  Google Scholar 

  54. De Ferrari, G. M. et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur. Heart J. 32, 847–855 (2011).

    Article  CAS  PubMed  Google Scholar 

  55. Schwartz, P. J. & De Ferrari, G. M. Sympathetic-parasympathetic interaction in health and disease: abnormalities and relevance in heart failure. Heart Fail. Rev. 16, 101–107 (2011).

    Article  PubMed  Google Scholar 

  56. Billman, G. E., Schwartz, P. J. & Stone, H. L. Baroreceptor reflex control of heart rate: a predictor of sudden cardiac death. Circulation 66, 874–880 (1982).

    Article  CAS  PubMed  Google Scholar 

  57. Schwartz, P. J. et al. Autonomic mechanisms and sudden death: new insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 78, 969–979 (1988).

    Article  CAS  PubMed  Google Scholar 

  58. La Rovere, M. T. et al. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 351, 478–484 (1998).

    Article  CAS  PubMed  Google Scholar 

  59. La Rovere, M. T. et al. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation 103, 2072–2077 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Vanoli, E. et al. Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction. Circ. Res. 68, 1471–1481 (1991).

    Article  CAS  PubMed  Google Scholar 

  61. Billman, G. E. Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training. Am. J. Physiol. Heart Circ. Physiol. 297, H1171–H1193 (2009).

    Article  CAS  PubMed  Google Scholar 

  62. Schwartz, P. J. et al. Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome: a worldwide report. Circulation 84, 503–511 (1991).

    Article  CAS  PubMed  Google Scholar 

  63. Schwartz, P. J. et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation 109, 1826–1833 (2004).

    Article  PubMed  Google Scholar 

  64. Collura, C. A., Johnson, J. N., Moir, C. & Ackerman, M. J. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. Heart Rhythm 6, 752–759 (2009).

    Article  PubMed  Google Scholar 

  65. Coleman, M. A. 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. 5, 782–788 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Schwartz, P. J. & Ackerman, M. J. The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy. Eur. Heart J. 34, 3109–3116 (2013).

    Article  PubMed  Google Scholar 

  67. Schwartz, P. J. Efficacy of left cardiac sympathetic denervation has an unforeseen side effect: medicolegal complications. Heart Rhythm 7, 1330–1332 (2010).

    Article  PubMed  Google Scholar 

  68. Wilde, A. A. M. et al. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N. Engl. J. Med. 358, 2024–2029 (2008).

    Article  CAS  PubMed  Google Scholar 

  69. Roses-Noguer, F., Jarman, J. W., Clague, J. R. & Till, J. Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 11, 58–66 (2014).

    Article  PubMed  Google Scholar 

  70. Atallah, J. et al. Video-assisted thorascopic cardiac denervation: a potential novel therapeutic option for children with intractable ventricular arrhythmias. Ann. Thorac. Surg. 86, 1620–1625 (2008).

    Article  PubMed  Google Scholar 

  71. Schwartz, P. J. et al. Effect of ventricular fibrillation complicating acute myocardial infarction on long term prognosis: importance of the site of infarction. Am. J. Cardiol. 56, 384–389 (1985).

    Article  CAS  PubMed  Google Scholar 

  72. Schwartz, P. J. et al. Prevention of sudden cardiac death after a first myocardial infarction by pharmacologic or surgical antiadrenergic interventions. J. Cardiovasc. Electrophysiol. 3, 2–16 (1992).

    Article  Google Scholar 

  73. Bourke, T. et al. Neuraxial modulation for refractory ventricular arrhythmias: value of thoracic epidural anesthesia and surgical left cardiac sympathetic denervation. Circulation 121, 2255–2262 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Ajijola, O. A. et al. Bilateral cardiac sympathetic denervation for the management of electrical storm. J. Am. Coll. Cardiol. 59, 91–92 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Vaseghi, M. et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm 11, 360–366 (2014).

    Article  PubMed  Google Scholar 

  76. Boogers, M. J. et al. Cardiac sympathetic denervation assessed with 123-iodine metaiodobenzylguanidine imaging predicts ventricular arrhythmias in implantable cardioverter-defibrillator patients. J. Am. Coll. Cardiol. 55, 2769–2777 (2010).

    Article  PubMed  Google Scholar 

  77. Watanabe, H. et al. Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 10, 542–547 (2013).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The author is grateful to Pinuccia De Tomasi BS (Association for the Study and the Prevention of Life-threatening Arrhythmias and Sudden Cardiac Death, Milan, Italy) for expert editorial support.

Author information

Authors and Affiliations

  1. Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Casa di Cura San Carlo, Via Pier Lombardo 22, 20135, Milan, Italy

    Peter J. Schwartz

Authors
  1. Peter J. Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter J. Schwartz.

Ethics declarations

Competing interests

The author declares no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwartz, P. Cardiac sympathetic denervation to prevent life-threatening arrhythmias. Nat Rev Cardiol 11, 346–353 (2014). https://doi.org/10.1038/nrcardio.2014.19

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2014.19

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing