Skip to main content

Introduction

A Second Look at the Autonomic Nervous System: Repurposing Our Lessons Learned

  • Chapter
  • First Online:
Heart Failure Management: The Neural Pathways

Abstract

The key function of the autonomic nervous system (ANS) in normal cardiac physiology has been known for more than 50 years. Early studies in the 1960s and 1970s by Braunwald and colleagues demonstrated the ANS’ role in the maintenance of cardiac output at rest and in response to exercise through modulation of heart rate, contractility, preload, and afterload [1, 2]. Abnormal hyperactivity of the sympathetic nervous system (SNS) and simultaneous dysfunction of the parasympathetic nervous system in heart disease were also recognized during this time period [1–4]. Additional population studies in heart failure (HF) patients showed an association of SNS activation with exercise capacity, hemodynamics, degree of left ventricular dysfunction, as well as mortality, establishing the critical impact of the ANS in cardiovascular dysregulation in the heart failure syndrome [5–9]. However it remained unclear if ANS activation played a truly causative role in myocardial deterioration rather than serving as a marker of the body’s attempt to maintain homeostasis in the face of a failing heart.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Braunwald E. Regulation of the circulation (second of two parts). N Engl J Med. 1974;290:1420–5.

    Article  CAS  PubMed  Google Scholar 

  2. Braunwald E. Regulation of the circulation. I. N Engl J Med. 1974;290:1124–9.

    Article  CAS  PubMed  Google Scholar 

  3. Braunwald E, Chidsey CA. The adrenergic nervous system in the control of the normal and failing heart. Proc R Soc Med. 1965;58:1063–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Eckberg DL, Drabinsky M, Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971;285:877–83.

    Article  CAS  PubMed  Google Scholar 

  5. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–23.

    Article  CAS  PubMed  Google Scholar 

  6. Chidsey CA, Harrison DC, Braunwald E. Augmentation of the plasma nor-epinephrine response to exercise in patients with congestive heart failure. N Engl J Med. 1962;267:650–4.

    Article  CAS  PubMed  Google Scholar 

  7. Thomas JA, Marks BH. Plasma norepinephrine in congestive heart failure. Am J Cardiol. 1978;41:233–43.

    Article  CAS  PubMed  Google Scholar 

  8. Levine TB, Francis GS, Goldsmith SR, Simon AB, Cohn JN. Activity of the sympathetic nervous system and renin-angiotensin system assessed by plasma hormone levels and their relation to hemodynamic abnormalities in congestive heart failure. Am J Cardiol. 1982;49:1659–66.

    Article  CAS  PubMed  Google Scholar 

  9. Francis GS, Goldsmith SR, Cohn JN. Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J. 1982;104:725–31.

    Article  CAS  PubMed  Google Scholar 

  10. Mann DL, Bristow MR. Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation. 2005;111:2837–49.

    Article  PubMed  Google Scholar 

  11. Katz AM. The “modern” view of heart failure: how did we get here? Circ Heart Fail. 2008;1:63–71.

    Article  CAS  PubMed  Google Scholar 

  12. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986;314:1547–52.

    Article  CAS  PubMed  Google Scholar 

  13. Hellawell JL, Margulies KB. Myocardial reverse remodeling. Cardiovasc Ther. 2012;30:172–81.

    Article  CAS  PubMed  Google Scholar 

  14. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349–55.

    Article  CAS  PubMed  Google Scholar 

  15. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13.

    Google Scholar 

  16. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–7.

    Google Scholar 

  17. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.

    Article  CAS  PubMed  Google Scholar 

  18. Swedberg K, Hjalmarson A, Waagstein F, Wallentin I. Beneficial effects of long-term beta-blockade in congestive cardiomyopathy. Br Heart J. 1980;44:117–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.

    Article  CAS  PubMed  Google Scholar 

  20. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362:772–6.

    Article  CAS  PubMed  Google Scholar 

  21. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893–906.

    Article  CAS  PubMed  Google Scholar 

  22. Mehra MR, Uber PA, Francis GS. Heart failure therapy at a crossroad: are there limits to the neurohormonal model? J Am Coll Cardiol. 2003;41:1606–10.

    Article  PubMed  Google Scholar 

  23. Cohn JN, Tognoni G, Valsartan Heart Failure Trial I. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.

    Article  CAS  PubMed  Google Scholar 

  24. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.

    Article  PubMed  Google Scholar 

  25. Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385:812–24.

    Article  PubMed  Google Scholar 

  26. Beadle RM, Williams LK, Kuehl M, et al. Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy. JACC Heart Fail. 2015;3:202–11.

    Article  PubMed  Google Scholar 

  27. Jorsal A, Wiggers H, Holmager P, et al. A protocol for a randomised, double-blind, placebo-controlled study of the effect of LIraglutide on left VEntricular function in chronic heart failure patients with and without type 2 diabetes (The LIVE Study). BMJ Open. 2014;4:e004885.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Margulies KB, Perrella MA, McKinley LJ, Burnett Jr JC. Angiotensin inhibition potentiates the renal responses to neutral endopeptidase inhibition in dogs with congestive heart failure. J Clin Invest. 1991;88:1636–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Allarakhia M. Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases. Drug Des Devel Ther. 2013;7:753–66.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049–57.

    Article  CAS  PubMed  Google Scholar 

  31. Jessup M. Neprilysin inhibition--a novel therapy for heart failure. N Engl J Med. 2014;371:1062–4.

    Article  PubMed  Google Scholar 

  32. Costanzo MR, Saltzberg MT, Jessup M, Teerlink JR, Sobotka PA, Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure I. Ultrafiltration is associated with fewer rehospitalizations than continuous diuretic infusion in patients with decompensated heart failure: results from UNLOAD. J Cardiac Fail. 2010;16:277–84.

    Google Scholar 

  33. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.

    Article  CAS  PubMed  Google Scholar 

  34. Tang AS, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010;363:2385–95.

    Article  CAS  PubMed  Google Scholar 

  35. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361:1329–38.

    Article  PubMed  Google Scholar 

  36. Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008;52:1834–43.

    Article  PubMed  Google Scholar 

  37. Patel HC, Rosen SD, Lindsay A, Hayward C, Lyon AR, di Mario C. Targeting the autonomic nervous system: measuring autonomic function and novel devices for heart failure management. Int J Cardiol. 2013;170:107–17.

    Article  PubMed  Google Scholar 

  38. Cohn JN, Pfeffer MA, Rouleau J, et al. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003;5:659–67.

    Article  CAS  PubMed  Google Scholar 

  39. Zhang DY, Anderson AS. The sympathetic nervous system and heart failure. Cardiol Clin. 2014;32:33–45, vii.

    Article  PubMed  Google Scholar 

  40. Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J. The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J Am Coll Cardiol. 2009;54:1747–62.

    Article  CAS  PubMed  Google Scholar 

  41. Birks EJ, George RS, Hedger M, et al. Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: a prospective study. Circulation. 2011;123:381–90.

    Article  CAS  PubMed  Google Scholar 

  42. Kamalakkannan G, Petrilli CM, George I, et al. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant Off Publ Int Soc Heart Transplant. 2008;27:457–61.

    Article  Google Scholar 

  43. Gold MR, van Veldhuisen DJ, Mann DL. Vagal nerve stimulation for heart failure: new pieces to the puzzle? Eur J Heart Fail. 2015;17:125–7.

    Article  PubMed  Google Scholar 

  44. Courand PY, Feugier P, Workineh S, Harbaoui B, Bricca G, Lantelme P. Baroreceptor stimulation for resistant hypertension: first implantation in France and literature review. Arch Cardiovasc Dis. 2014;107:690–6.

    Article  PubMed  Google Scholar 

  45. Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, Klug DLE, Müller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC Heart Fail. 2015;3(6):487–96.

    Article  PubMed  Google Scholar 

  46. Singh JP, Kandala J, Camm AJ. Non-pharmacological modulation of the autonomic tone to treat heart failure. Eur Heart J. 2014;35:77–85.

    Article  PubMed  Google Scholar 

  47. Zannad F, De Ferrari GM, Tuinenburg AE, et al. 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. 2015;36:425–33.

    Article  PubMed  Google Scholar 

  48. Ben-Menachem E, Revesz D, Simon BJ, Silberstein S. Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol Off J Eur Fed Neurol Soc. 2015;22(9):1260–8.

    CAS  Google Scholar 

  49. Wang Z, Yu L, Chen M, Wang S, Jiang H. Transcutaneous electrical stimulation of auricular branch of vagus nerve: a noninvasive therapeutic approach for post-ischemic heart failure. Int J Cardiol. 2014;177:676–7.

    Article  PubMed  Google Scholar 

  50. Tse HF, Turner S, Sanders P, et al. Thoracic spinal cord stimulation for heart failure as a restorative treatment (SCS HEART study): first-in-man experience. Heart Rhythm Off J Heart Rhythm Soc. 2015;12:588–95.

    Article  Google Scholar 

  51. Torre-Amione G, Alo K, Estep JD, et al. Spinal cord stimulation is safe and feasible in patients with advanced heart failure: early clinical experience. Eur J Heart Fail. 2014;16:788–95.

    Article  PubMed  Google Scholar 

  52. Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–401.

    Article  CAS  PubMed  Google Scholar 

  53. Mahfoud F, Luscher TF, Andersson B, et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J. 2013;34:2149–57.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mariell L. Jessup MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Vorovich, E., Jessup, M.L. (2016). Introduction. In: Gronda, E., Vanoli, E., Costea, A. (eds) Heart Failure Management: The Neural Pathways. Springer, Cham. https://doi.org/10.1007/978-3-319-24993-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-24993-3_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-24991-9

  • Online ISBN: 978-3-319-24993-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics