Skip to main content
SpringerLink
Log in

Autonomic Dysregulation as a Therapeutic Target for Acute HF

  • Heart Failure (W Tang, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

Despite major advances that have led to effective therapeutic modalities for the treatment of heart failure (HF), this syndrome has continued to be a staggering health problem associated with significant mortality and morbidity. The increasing number of hospital admissions and readmissions related to acute HF continues to pose a fiscal challenge leading to constant interest in development of novel approaches. These point to multiple areas of unmet needs especially in acute HF, thus, necessitating further efforts to develop novel strategies for prevention and treatment of acute HF. One area of continuing focus is targeting the role of autonomic imbalance associated with the development of HF. Autonomic dysregulation, manifested by increased sympathetic drive and reduced parasympathetic activity, has been recognized as a mediator of increased mortality and morbidity in HF and myocardial infarction. Furthermore, vagal withdrawal has been shown to precede acute decompensation, though whether this represents cause or effect is unknown. This review discusses the potential role of autonomic dysregulation as a therapeutic modality for patients with acute decompensated HF.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

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

  1. Mark AL. Sympathetic dysregulation in HF: mechanisms and therapy. Clin Cardiol. 1995;18(3 Suppl I):I3–8.

    CAS  PubMed  Google Scholar 

  2. Schwartz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD. Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation. 1988;78(4):969–79.

    Article  CAS  PubMed  Google Scholar 

  3. Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O, et al. Arterial baroreflex modulation of heart rate in chronic HF: clinical and hemodynamic correlates and prognostic implications. Circulation. 1997;96(10):3450–8.

    Article  CAS  PubMed  Google Scholar 

  4. Klein HU, Ferrari GM. Vagus nerve stimulation: a new approach to reduce HF. Cardiol J. 2010;17(6):638–44.

    PubMed  Google Scholar 

  5. Kaye DM, Lefkovits J, Jennings GL, Bergin P, Broughton A, Esler MD. Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol. 1995;26(5):1257–63. doi:10.1016/0735-1097(95)00332-0.

    Article  CAS  PubMed  Google Scholar 

  6. Floras JS. Sympathetic nervous system activation in human HF: clinical implications of an updated model. J Am Coll Cardiol. 2009;54(5):375–85. doi:10.1016/j.jacc.2009.03.061.

    Article  CAS  PubMed  Google Scholar 

  7. Burchell AE, Sobotka PA, Hart EC, Nightingale AK, Dunlap ME. Chemohypersensitivity and autonomic modulation of venous capacitance in the pathophysiology of acute decompensated HF. Current HF Reports. 2013;10(2):139–46. doi:10.1007/s11897-013-0135-y.

    CAS  Google Scholar 

  8. Fallick C, Sobotka PA, Dunlap ME. Sympathetically mediated changes in capacitance: redistribution of the venous reservoir as a cause of decompensation. Circ Heart Fail. 2011;4(5):669–75. doi:10.1161/CIRCHEARTFAILURE.111.961789.

    Article  PubMed  Google Scholar 

  9. Dibner-Dunlap ME, Thames MD. Baroreflex control of renal sympathetic nerve activity is preserved in HF despite reduced arterial baroreceptor sensitivity. Circ Res. 1989;65(6):1526–35.

    Article  CAS  PubMed  Google Scholar 

  10. Dibner-Dunlap ME, Thames MD. Control of sympathetic nerve activity by vagal mechanoreflexes is blunted in HF. Circulation. 1992;86(6):1929–34.

    Article  CAS  PubMed  Google Scholar 

  11. Roveda F, Middlekauff HR, Rondon MU, Reis SF, Souza M, Nastari L, et al. The effects of exercise training on sympathetic neural activation in advanced HF: a randomized controlled trial. J Am Coll Cardiol. 2003;42(5):854–60.

    Article  PubMed  Google Scholar 

  12. O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, et al. Efficacy and safety of exercise training in patients with chronic HF: HF-ACTION randomized controlled trial. Jama. 2009;301(14):1439–50. doi:10.1001/jama.2009.454.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Kleiber AC, Zheng H, Schultz HD, Peuler JD, Patel KP. Exercise training normalizes enhanced glutamate-mediated sympathetic activation from the PVN in HF. Am J Physiol Regul Integr Comp Physiol. 2008;294(6):R1863–72. doi:10.1152/ajpregu.00757.2007.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Liu JL, Irvine S, Reid IA, Patel KP, Zucker IH. Chronic exercise reduces sympathetic nerve activity in rabbits with pacing-induced HF: a role for angiotensin II. Circulation. 2000;102(15):1854–62.

    Article  CAS  PubMed  Google Scholar 

  15. Patel KP, Salgado HC, Liu X, Zheng H. Exercise training normalizes the blunted central component of the baroreflex in rats with HF: role of the PVN. Am J Physiol Heart Circ Physiol. 2013;305(2):H173–81. doi:10.1152/ajpheart.00009.2013. The findings in this study underscore the importance of Exercise training to restore sympathetic outflow in heart failure, and mechanistic insights of baroreflex responses in heart failure.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Moe GW, Albernaz A, Naik GO, Kirchengast M, Stewart DJ. Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental HF. Cardiovasc Res. 1998;39(3):571–9.

    Article  CAS  PubMed  Google Scholar 

  17. McConnell PI, Olson CE, Patel KP, Blank DU, Olivari MT, Gallagher KP, et al. Chronic endothelin blockade in dogs with pacing-induced HF: possible modulation of sympathoexcitation. J Card Fail. 2000;6(1):56–65.

    Article  CAS  PubMed  Google Scholar 

  18. Liu JL, Pliquett RU, Brewer E, Cornish KG, Shen YT, Zucker IH. Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with HF. Am J Physiol Regul Integr Comp Physiol. 2001;280(6):R1906–13.

    CAS  PubMed  Google Scholar 

  19. Tsuchiyama Y, Kasamatsu K, Hano T, Nishio I. Acute effect of endothelin AB antagonist on sympathetic outflow in conscious rats with HF. Circ J. 2002;66(9):841–5.

    Article  CAS  PubMed  Google Scholar 

  20. Cody RJ, Franklin KW, Kluger J, Laragh JH. Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive HF: effects of acute and long-term converting-enzyme inhibition. Circulation. 1982;66(1):135–42.

    Article  CAS  PubMed  Google Scholar 

  21. Dibner-Dunlap ME, Smith ML, Kinugawa T, Thames MD. Enalaprilat augments arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in patients with HF. J Am Coll Cardiol. 1996;27(2):358–64.

    Article  CAS  PubMed  Google Scholar 

  22. Moore JP, Hainsworth R, Drinkhill MJ. Phasic negative intrathoracic pressures enhance the vascular responses to stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized dogs. J Physiol. 2004;555(Pt 3):815–24. doi:10.1113/jphysiol.2003.057968.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Sun SY, Wang W, Zucker IH, Schultz HD. Enhanced peripheral chemoreflex function in conscious rabbits with pacing-induced HF. J Appl Physiol (1985). 1999;86(4):1264–72.

    CAS  Google Scholar 

  24. Schultz HD, Li YL, Ding Y. Arterial chemoreceptors and sympathetic nerve activity: implications for hypertension and HF. Hypertension. 2007;50(1):6–13. doi:10.1161/HYPERTENSIONAHA.106.076083.

    Article  CAS  PubMed  Google Scholar 

  25. Dunlap ME, Bibevski S, Rosenberry TL, Ernsberger P. Mechanisms of altered vagal control in HF: influence of muscarinic receptors and acetylcholinesterase activity. Am J Physiol Heart Circ Physiol. 2003;285(4):H1632–40. doi:10.1152/ajpheart.01051.2002.

    Article  CAS  PubMed  Google Scholar 

  26. Bibevski S, Dunlap ME. Ganglionic mechanisms contribute to diminished vagal control in HF. Circulation. 1999;99(22):2958–63.

    Article  CAS  PubMed  Google Scholar 

  27. Kinugawa T, Dibner-Dunlap ME. Altered vagal and sympathetic control of heart rate in left ventricular dysfunction and HF. Am J Physiol. 1995;268(2 Pt 2):R310–16.

    CAS  PubMed  Google Scholar 

  28. Eckberg DL, Drabinsky M, Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971;285(16):877–83. doi:10.1056/NEJM197110142851602.

    Article  CAS  PubMed  Google Scholar 

  29. Binkley PF, Haas GJ, Starling RC, Nunziata E, Hatton PA, Leier CV, et al. Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive HF. J Am Coll Cardiol. 1993;21(3):655–61.

    Article  CAS  PubMed  Google Scholar 

  30. DiBona GF, Jones SY, Sawin LL. Angiotensin receptor antagonist improves cardiac reflex control of renal sodium handling in HF. Am J Physiol. 1998;274(2 Pt 2):H636–41.

    CAS  PubMed  Google Scholar 

  31. Sal’nikov EV. Heart rate variability in rats with experimental chronic HF and long-term exposure to beta-adrenoblockers. Bull Exp Biol Med. 2009;147(2):181–4.

    Article  PubMed  Google Scholar 

  32. Goldsmith RL, Bigger JT, Bloomfield DM, Krum H, Steinman RC, Sackner-Bernstein J, et al. Long-term carvedilol therapy increases parasympathetic nervous system activity in chronic congestive HF. Am J Cardiol. 1997;80(8):1101–4.

    Article  CAS  PubMed  Google Scholar 

  33. Pousset F, Copie X, Lechat P, Jaillon P, Boissel JP, Hetzel M, et al. Effects of bisoprolol on heart rate variability in HF. Am J Cardiol. 1996;77(8):612–7.

    Article  CAS  PubMed  Google Scholar 

  34. Lin LY, Hwang JJ, Lai LP, Chan HL, Du CC, Tseng YZ, et al. Restoration of heart rate turbulence by titrated beta-blocker therapy in patients with advanced congestive HF: positive correlation with enhanced vagal modulation of heart rate. J Cardiovasc Electrophysiol. 2004;15(7):752–6. doi:10.1046/j.1540-8167.2004.03289.x.

    Article  PubMed  Google Scholar 

  35. Dibner-Dunlap ME, Eckberg DL, Magid NM, Cintron-Trevino NM. The long-term increase of baseline and reflexly augmented levels of human vagal-cardiac nervous activity induced by scopolamine. Circulation. 1985;71(4):797–804.

    Article  CAS  PubMed  Google Scholar 

  36. Casadei B, Conway J, Forfar C, Sleight P. Effect of low doses of scopolamine on RR interval variability, baroreflex sensitivity, and exercise performance in patients with chronic HF. Heart. 1996;75(3):274–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Androne AS, Hryniewicz K, Goldsmith R, Arwady A, Katz SD. Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic HF. Heart. 2003;89(8):854–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Okazaki Y, Zheng C, Li M, Sugimachi M. Effect of the cholinesterase inhibitor donepezil on cardiac remodeling and autonomic balance in rats with HF. J Physiol Sci. 2010;60(1):67–74. doi:10.1007/s12576-009-0071-5.

    Article  CAS  PubMed  Google Scholar 

  39. Janssens S, Pokreisz P, Schoonjans L, Pellens M, Vermeersch P, Tjwa M, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res. 2004;94(9):1256–62. doi:10.1161/01.RES.0000126497.38281.23.

    Article  CAS  PubMed  Google Scholar 

  40. Fraccarollo D, Widder JD, Galuppo P, Thum T, Tsikas D, Hoffmann M, et al. Improvement in left ventricular remodeling by the endothelial nitric oxide synthase enhancer AVE9488 after experimental myocardial infarction. Circulation. 2008;118(8):818–27. doi:10.1161/CIRCULATIONAHA.107.717702.

    Article  CAS  PubMed  Google Scholar 

  41. El-Armouche A, Wahab A, Wittkopper K, Schulze T, Bottcher F, Pohlmann L, et al. The new HNO donor, 1-nitrosocyclohexyl acetate, increases contractile force in normal and beta-adrenergically desensitized ventricular myocytes. Biochem Biophys Res Commun. 2010;402(2):340–4. doi:10.1016/j.bbrc.2010.10.030.

    Article  CAS  PubMed  Google Scholar 

  42. Arcaro A, Lembo G, Tocchetti CG. Nitroxyl (HNO) for treatment of acute HF. Curr Heart Fail Rep. 2014;11(3):227–35. doi:10.1007/s11897-014-0210-z.

    Article  CAS  PubMed  Google Scholar 

  43. Sabbah HN, Tocchetti CG, Wang M, Daya S, Gupta RC, Tunin RS, et al. Nitroxyl (HNO): a novel approach for the acute treatment of HF. Circ Heart Fail. 2013;6(6):1250–8. doi:10.1161/CIRCHEARTFAILURE.113.000632. This paper was the first cell to human transformation of a pure HNO donor suggesting the potential eficacy and usefulness this pharmacologic approach to improve function of the failing heart.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Cuffe MS, Califf RM, Adams Jr KF, Benza R, Bourge R, Colucci WS, et al. Short-term intravenous milrinone for acute exacerbation of chronic HF: a randomized controlled trial. JAMA. 2002;287(12):1541–7. doi:joc11563 [pii].

    Article  CAS  PubMed  Google Scholar 

  45. O’Connor CM, Gattis WA, Uretsky BF, Adams Jr KF, McNulty SE, Grossman SH, et al. Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced HF: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1999;138(1 Pt 1):78–86.

    Article  PubMed  Google Scholar 

  46. Thackray S, Easthaugh J, Freemantle N, Cleland JG. The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with HF-a meta-regression analysis. Eur J Heart Fail. 2002;4(4):515–29.

    Article  CAS  PubMed  Google Scholar 

  47. Packer M, Colucci W, Fisher L, Massie BM, Teerlink JR, Young J, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated HF. JACC Heart Fail. 2013;1(2):103–11. doi:10.1016/j.jchf.2012.12.004.

    Article  PubMed  Google Scholar 

  48. Teerlink JR, Metra M, Felker GM, Ponikowski P, Voors AA, Weatherley BD, et al. Relaxin for the treatment of patients with acute HF (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. 2009;373(9673):1429–39. doi:10.1016/S0140-6736(09)60622-X.

    Article  CAS  PubMed  Google Scholar 

  49. Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute HF (RELAX-AHF): a randomised, placebo-controlled trial. Lancet. 2013;381(9860):29–39. doi:10.1016/S0140-6736(12)61855-8. This study provides supportive evidence for beneficial of serelaxin in improving symptoms and other outcomes in selected patients with heart failure, consistent with the emerging concept that acute heart failure is associated with damage to multiple organ systems, and that protection from the harmful effects of these episodes can have favorable effects on survival.

    Article  CAS  PubMed  Google Scholar 

  50. Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett Jr JC. Cardiorenal actions of TRV120027, a novel ss-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and HF canines: a novel therapeutic strategy for acute HF. Circ Heart Fail. 2011;4(6):770–8. doi:10.1161/CIRCHEARTFAILURE.111.962571.

    Article  CAS  PubMed  Google Scholar 

  51. Soergel DG, Subach RA, Cowan CL, Violin JD, Lark MW. First clinical experience with TRV027: pharmacokinetics and pharmacodynamics in healthy volunteers. J Clin Pharmacol. 2013;53(9):892–9. doi:10.1002/jcph.111.

    Article  CAS  PubMed  Google Scholar 

  52. Bristow MR. Beta-adrenergic receptor blockade in chronic HF. Circulation. 2000;101(5):558–69.

    Article  CAS  PubMed  Google Scholar 

  53. Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, et al. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with HF: findings from the OPTIMIZE-HF program. J Am Coll Cardiol. 2008;52(3):190–9. doi:10.1016/j.jacc.2008.03.048.

    Article  CAS  PubMed  Google Scholar 

  54. Butler J, Young JB, Abraham WT, Bourge RC, Adams Jr KF, Clare R, et al. Beta-blocker use and outcomes among hospitalized HF patients. J Am Coll Cardiol. 2006;47(12):2462–9. doi:10.1016/j.jacc.2006.03.030.

    Article  CAS  PubMed  Google Scholar 

  55. Funakoshi K, Hosokawa K, Kishi T, Ide T, Sunagawa K. Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function. J Card Fail. 2014;20(1):53–9. doi:10.1016/j.cardfail.2013.11.007.

    Article  PubMed  Google Scholar 

  56. Dunlap ME, Tang WH. HF notwithstanding ejection fraction (HFnEF)—a possible unifying hypothesis? J Card Fail. 2014;20(1):60–2. doi:10.1016/j.cardfail.2013.12.006.

    Article  PubMed  Google Scholar 

  57. Kaye DM, Jennings GL, Dart AM, Esler MD. Differential effect of acute baroreceptor unloading on cardiac and systemic sympathetic tone in congestive HF. J Am Coll Cardiol. 1998;31(3):583–7.

    Article  CAS  PubMed  Google Scholar 

  58. Schrier RW, Berl T, Anderson RJ. Osmotic and nonosmotic control of vasopressin release. Am J Physiol. 1979;236(4):F321–32.

    CAS  PubMed  Google Scholar 

  59. Goldsmith SR, Elkayam U, Haught WH, Barve A, He W. Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated HF: a dose-ranging pilot study. J Card Fail. 2008;14(8):641–7. doi:10.1016/j.cardfail.2008.06.003.

    Article  CAS  PubMed  Google Scholar 

  60. Udelson JE, Bilsker M, Hauptman PJ, Sequeira R, Thomas I, O’Brien T, et al. A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with HF and systolic dysfunction. J Card Fail. 2011;17(12):973–81. doi:10.1016/j.cardfail.2011.08.005.

    Article  CAS  PubMed  Google Scholar 

  61. Felker GM, Mentz RJ. Diuretics and ultrafiltration in acute decompensated HF. J Am Coll Cardiol. 2012;59(24):2145–53. doi:10.1016/j.jacc.2011.10.910.

    Article  CAS  PubMed  Google Scholar 

  62. Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, et al. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated HF. J Am Coll Cardiol. 2007;49(6):675–83. doi:10.1016/j.jacc.2006.07.073.

    Article  CAS  PubMed  Google Scholar 

  63. Marenzi G, Grazi S, Giraldi F, Lauri G, Perego G, Guazzi M, et al. Interrelation of humoral factors, hemodynamics, and fluid and salt metabolism in congestive HF: effects of extracorporeal ultrafiltration. Am J Med. 1993;94(1):49–56.

    Article  CAS  PubMed  Google Scholar 

  64. Bart BA, Goldsmith SR, Lee KL, Givertz MM, O’Connor CM, Bull DA, et al. Ultrafiltration in decompensated HF with cardiorenal syndrome. N Engl J Med. 2012;367(24):2296–304. doi:10.1056/NEJMoa1210357.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm M, Sobotka PA. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial. Circulation. 2012;126(25):2976–82. doi:10.1161/CIRCULATIONAHA.112.130880.

    Article  CAS  PubMed  Google Scholar 

  66. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59(10):901–9. doi:10.1016/j.jacc.2011.11.034.

    Article  PubMed  Google Scholar 

  67. Verloop WL, Beeftink MM, Nap A, Bots ML, Velthuis BK, Appelman YE, et al. Renal denervation in HF with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in HF with nOrmal Lv Ejection fraction) trial. Eur J Heart Fail. 2013;15(12):1429–37. doi:10.1093/eurjhf/hft119.

    Article  CAS  PubMed  Google Scholar 

  68. Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393–401. doi:10.1056/NEJMoa1402670.

    Article  CAS  PubMed  Google Scholar 

  69. La Rovere MT, Bigger Jr JT, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet. 1998;351(9101):478–84.

    Article  PubMed  Google Scholar 

  70. Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic HF in CIBIS II Trial. Circulation. 2001;103(10):1428–33.

    Article  CAS  PubMed  Google Scholar 

  71. Schwartz PJ, De Ferrari GM, Sanzo A, Landolina M, Rordorf R, Raineri C, et al. Long term vagal stimulation in patients with advanced HF: first experience in man. Eur J Heart Fail. 2008;10(9):884–91. doi:10.1016/j.ejheart.2008.07.016.

    Article  PubMed  Google Scholar 

  72. De Ferrari GM, Crijns HJ, Borggrefe M, Milasinovic G, Smid J, Zabel M, et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic HF. Eur Heart J. 2011;32(7):847–55. doi:10.1093/eurheartj/ehq391.

    Article  PubMed  Google Scholar 

  73. Hauptman PJ, Schwartz PJ, Gold MR, Borggrefe M, Van Veldhuisen DJ, Starling RC, et al. Rationale and study design of the increase of vagal tone in HF study: INOVATE-HF. Am Heart J. 2012;163(6):954–62 e1. doi:10.1016/j.ahj.2012.03.021.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Anju Bhardwaj declares no potential conflicts of interest.

Mark E. Dunlap reports grants from Medtronic, Inc. and BioControl Medical, Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Heart and Vascular Center, MetroHealth Campus of Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA

    Anju Bhardwaj MD & Mark E. Dunlap MD

Authors
  1. Anju Bhardwaj MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark E. Dunlap MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark E. Dunlap MD.

Additional information

This article is part of the Topical Collection on Heart Failure

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhardwaj, A., Dunlap, M.E. Autonomic Dysregulation as a Therapeutic Target for Acute HF. Curr Treat Options Cardio Med 17, 43 (2015). https://doi.org/10.1007/s11936-015-0403-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11936-015-0403-0

Keywords

Search

Navigation