Advertisement

Current Heart Failure Reports

, Volume 12, Issue 4, pp 284–293 | Cite as

Autonomic Regulation Therapy in Heart Failure

  • Una Buckley
  • Kalyanam Shivkumar
  • Jeffrey L. ArdellEmail author
Pathophysiology of Myocardial Failure (I Anand and M Patarroyo-Aponte, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pathophysiology of Myocardial Failure

Abstract

Autonomic regulation therapy (ART) is a rapidly emerging therapy in the management of congestive heart failure secondary to systolic dysfunction. Modulation of the cardiac neuronal hierarchy can be achieved with bioelectronics modulation of the spinal cord, cervical vagus, baroreceptor, or renal nerve ablation. This review will discuss relevant preclinical and clinical research in ART for systolic heart failure. Understanding mechanistically what is being stimulated within the autonomic nervous system by such device-based therapy and how the system reacts to such stimuli is essential for optimizing stimulation parameters and for the future development of effective ART.

Keywords

Heart failure Sympathetic modulation Vagus nerve stimulation Spinal cord stimulation Baroreceptor stimulation Renal denervation 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Jeffrey L. Ardell serves as a scientific advisor to Cyberonics, Inc. Kalyanam Shivkumar and Una Buckley declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of UCLA and the National Institutes of Health and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

All procedures performed in studies involving animals were in accordance with the ethical standards of the East Tennessee State University and the University of California Los Angeles.

Sources of Funding

This work was supported by the Heart, Lung and Blood Institute grants HL71830 (JLA) and HL84261 (KS) and by a private sector funding for studies related to neuromodulation provided in part by St. Jude Medical (JLA) and Cyberonics Inc (JLA).

Author Contributions

All authors contributed equally to researching data for this article, writing the manuscript, discussing of content, and approving the final version before submission.

References

  1. 1.
    Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129:e28–292.PubMedCrossRefGoogle Scholar
  2. 2.
    Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606–19.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol. 1993;22:6A–13.PubMedCrossRefGoogle Scholar
  4. 4.
    Mehta PA, Dubrey SW, McIntyre HF, et al. Improving survival in the 6 months after diagnosis of heart failure in the past decade: population-based data from the UK. Heart. 2009;95:1851–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311:806–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Wiener JM, Tilly J. Population ageing in the United States of America: implications for public programmes. Int J Epidemiol. 2002;31:776–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–53.PubMedCrossRefGoogle Scholar
  8. 8.
    Armour JA. Cardiac neuronal hierarchy in health and disease. Am J Physiol Regul Integr Comp Physiol. 2004;287:R262–71.PubMedCrossRefGoogle Scholar
  9. 9.
    Kember G, Armour JA, Zamir M. Neural control of heart rate: the role of neuronal networking. J Theor Biol. 2011;277:41–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Armour JA. Potential clinical relevance of the ‘little brain’ on the mammalian heart. Exp Physiol. 2008;93:165–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Ardell JL, Cardinal R, Vermeulen M, Armour JA. Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia. Am J Physiol Regul Integr Comp Physiol. 2009;297:R470–7.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Beaumont E, Salavatian S, Southerland EM, et al. Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function. J Physiol. 2013;591:4515–33.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology. 1992;42:1727–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Armour JA, Kember G. Cardiac sensory neurons. In: Armour JA, Ardell JL, editors. Basic and clinical neurocardiology. New York: Oxford University Press; 2004. p. 79–117.Google Scholar
  15. 15.
    Foreman RD. Mechanisms of cardiac pain. Annu Rev Physiol. 1999;61:143–67.PubMedCrossRefGoogle Scholar
  16. 16.
    Fu LW, Longhurst JC. Regulation of cardiac afferent excitability in ischemia. Handb Exp Pharmacol. 2009;194:185–225.Google Scholar
  17. 17.
    Fukada K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K. Cardiac innervation and sudden cardiac death. Circ Res. 2015;in press.Google Scholar
  18. 18.
    Zucker IH, Patel KP, Schultz HD. Neurohumoral stimulation. Heart Fail Clin. 2012;8:87–99.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Andresen MC, Kunze DL, Mendelowitz D. Central nervous system regulation of the heart. In: Armour JA, Ardell JL, editors. Basic and clinical neurocardiology. New York: Oxford University Press; 2004. p. 187–219.Google Scholar
  20. 20.
    Zucker IH, Gilmore JP. Reflex control of the circulation. Boca Raton: CRC Press; 1991.Google Scholar
  21. 21.
    Blinder KJ, Johnson TA, John Massari V. Negative inotropic vagal preganglionic neurons in the nucleus ambiguus of the cat: neuroanatomical comparison with negative chronotropic neurons utilizing dual retrograde tracers. Brain Res. 1998;804:325–30.PubMedCrossRefGoogle Scholar
  22. 22.
    Coote JH. Myths and realities of the cardiac vagus. J Physiol. 2013;591:4073–85.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    McAllen RM, Salo LM, Paton JF, Pickering AE. Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis. J Physiol. 2011;589:5801–18.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Hopkins DA, Armour JA. Localization of sympathetic postganglionic and parasympathetic preganglionic neurons which innervate different regions of the dog heart. J Comp Neurol. 1984;229:186–98.PubMedCrossRefGoogle Scholar
  25. 25.
    Randall WC. Efferent sympathetic innervation of the heart. In: Armour JA, Ardell JL, editors. Neurocardiology. New York: Oxford University Press; 1994. p. 77–94.Google Scholar
  26. 26.
    Gray AL, Johnson TA, Ardell JL, Massari VJ. Parasympathetic control of the heart. II. A novel interganglionic intrinsic cardiac circuit mediates neural control of heart rate. J Appl Physiol (1985). 2004;96:2273–8.CrossRefGoogle Scholar
  27. 27.
    Armour JA, Collier K, Kember G, Ardell JL. Differential selectivity of cardiac neurons in separate intrathoracic autonomic ganglia. Am J Physiol. 1998;274:R939–49.PubMedGoogle Scholar
  28. 28.
    Waldmann M, Thompson GW, Kember GC, Ardell JL, Armour JA. Stochastic behavior of atrial and ventricular intrinsic cardiac neurons. J Appl Physiol (1985). 2006;101:413–9.CrossRefGoogle Scholar
  29. 29.
    Florea VG, Cohn JN. The autonomic nervous system and heart failure. Circ Res. 2014;114:1815–26.PubMedCrossRefGoogle Scholar
  30. 30.
    Billman GE. A comprehensive review and analysis of 25 years of data from an in vivo canine model of sudden cardiac death: implications for future anti-arrhythmic drug development. Pharmacol Ther. 2006;111:808–35.PubMedCrossRefGoogle Scholar
  31. 31.
    Ajijola OA, Yagishita D, Reddy NK, et al. Remodeling of stellate ganglion neurons following spatially targeted myocardial infarction: neuropeptide and morphologic changes. Heart Rhythm Off J Heart Rhythm Soc. 2015;12(5):1027–35.Google Scholar
  32. 32.
    Macey PM, Wu P, Kumar R, et al. Differential responses of the insular cortex gyri to autonomic challenges. Auton Neurosci Basic Clin. 2012;168:72–81.CrossRefGoogle Scholar
  33. 33.
    Kember G, Armour JA, Zamir M. Neural control hierarchy of the heart has not evolved to deal with myocardial ischemia. Physiol Genomics. 2013;45:638–44.PubMedCrossRefGoogle Scholar
  34. 34.
    Vaseghi M, Gima J, Kanaan C, et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm. 2014;11:360–6.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    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.PubMedCrossRefGoogle Scholar
  36. 36.
    Bonaz B, Picq C, Sinniger V, Mayol JF, Clarencon D. Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2013;25:208–21.CrossRefGoogle Scholar
  37. 37.
    De Ferrari GM. Vagal stimulation in heart failure. J Cardiovasc Transl Res. 2014;7:310–20.PubMedCrossRefGoogle Scholar
  38. 38.
    Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex—linking immunity and metabolism. Nat Rev Endocrinol. 2012;8:743–54.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Brack KE, Winter J, Ng GA. Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation—tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure. Heart Fail Rev. 2013;18:389–408.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Ng GA. Vagal modulation of cardiac ventricular arrhythmia. Exp Physiol. 2014;99:295–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Shinlapawittayatorn K, Chinda K, Palee S, et al. Low-amplitude, left vagus nerve stimulation significantly attenuates ventricular dysfunction and infarct size through prevention of mitochondrial dysfunction during acute ischemia-reperfusion injury. Heart Rhythm. 2013;10:1700–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Huang J, Qian J, Yao W, et al. Vagus nerve stimulation reverses ventricular electrophysiological changes induced by hypersympathetic nerve activity. Exp Physiol. 2015;100:239–48.PubMedCrossRefGoogle Scholar
  43. 43.
    Vanoli E, De Ferrari GM, Stramba-Badiale M, Hull Jr SS, 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.PubMedCrossRefGoogle Scholar
  44. 44.
    Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K. Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation. 2004;109:120–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhang Y, Popovic ZB, Bibevski S, et al. Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model. Circ Heart Fail. 2009;2:692–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Beaumont E, Southerland EM, Hardwick JC, Ryan SE, KenKnight BH, Ardell JL. Chronic autonomic regulation therapy mitigates adverse remodeling induced by pressure overload in the guinea pig heart. Paper presented at: American College of Cardiology. Washington DC; 2014.Google Scholar
  47. 47.
    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.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang Z, Yu L, Wang S, et al. Chronic intermittent low-level transcutaneous electrical stimulation of auricular branch of vagus nerve improves left ventricular remodeling in conscious dogs with healed myocardial infarction. Circ Heart Fail. 2014;7:1014–21.PubMedCrossRefGoogle Scholar
  49. 49.
    McGuirt AS, Schmacht DC, Ardell JL. Autonomic interactions for control of atrial rate are maintained after SA nodal parasympathectomy. Am J Physiol. 1997;272:H2525–33.PubMedGoogle Scholar
  50. 50.
    Randall DC, Brown DR, McGuirt AS, Thompson GW, Armour JA, Ardell JL. Interactions within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol. 2003;285:R1066–75.PubMedCrossRefGoogle Scholar
  51. 51.
    Ryzi M, Brazdil M, Novak Z, et al. Long-term outcomes in patients after epilepsy surgery failure. Epilepsy Res. 2015;110:71–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Tisi G, Franzini A, Messina G, Savino M, Gambini O. Vagus nerve stimulation therapy in treatment-resistant depression: a series report. Psychiatry Clin Neurosci. 2014;68:606–11.PubMedCrossRefGoogle Scholar
  53. 53.
    Schwartz PJ, De Ferrari GM, Sanzo A, et al. Long term vagal stimulation in patients with advanced heart failure: first experience in man. Eur J Heart Fail. 2008;10:884–91.PubMedCrossRefGoogle Scholar
  54. 54.
    De Ferrari GM, Crijns HJ, Borggrefe M, et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011;32:847–55.PubMedCrossRefGoogle Scholar
  55. 55.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Premchand RK, Sharma K, Mittal S, et al. Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF Trial. J Card Fail. 2014;20(11):808–16.Google Scholar
  57. 57.
    Foreman RD, Linderoth B. Neural mechanisms of spinal cord stimulation. Int Rev Neurobiol. 2012;107:87–119.PubMedCrossRefGoogle Scholar
  58. 58.
    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.PubMedCrossRefGoogle Scholar
  59. 59.
    Mannheimer C, Camici P, Chester MR, 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.PubMedCrossRefGoogle Scholar
  60. 60.
    Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Borjesson M, Andrell P, Lundberg D, Mannheimer C. Spinal cord stimulation in severe angina pectoris—a systematic review based on the Swedish Council on Technology assessment in health care report on long-standing pain. Pain. 2008;140:501–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Kingma Jr JG, Linderoth B, Ardell JL, Armour JA, DeJongste MJ, Foreman RD. Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia. Auton Neurosci. 2001;91:47–54.PubMedCrossRefGoogle Scholar
  63. 63.
    Ardell JL, Cardinal R, Beaumont E, Vermeulen M, Smith FM, Andrew Armour J. Chronic spinal cord stimulation modifies intrinsic cardiac synaptic efficacy in the suppression of atrial fibrillation. Auton Neurosci Basic Clin. 2014;186:38–44.CrossRefGoogle Scholar
  64. 64.
    Gibbons DD, Southerland EM, Hoover DB, Beaumont E, Armour JA, Ardell JL. Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias. Am J Physiol Regul Integr Comp Physiol. 2012;302:R357–64.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Lopshire JC, Zhou X, Dusa C, et al. Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model. Circulation. 2009;120:286–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Southerland EM, Gibbons DD, Smith SB, et al. Activated cranial cervical cord neurons affect left ventricular infarct size and the potential for sudden cardiac death. Auton Neurosci. 2012;169:34–42.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Southerland EM, Milhorn DM, Foreman RD, et al. Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons. Am J Physiol Heart Circ Physiol. 2007;292:H311–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Ding X, Ardell JL, Hua F, et al. Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: effect on substance P release from rat spinal cord. Am J Physiol Regul Integr Comp Physiol. 2008;294:R93–101.PubMedCrossRefGoogle Scholar
  69. 69.
    Ding X, Hua F, Sutherly K, Ardell JL, Williams CA. C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1519–28.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Foreman RD, Linderoth B, Ardell JL, et al. Modulation of intrinsic cardiac neurons by spinal cord stimulation: implications for its therapeutic use in angina pectoris. Cardiovasc Res. 2000;47:367–75.PubMedCrossRefGoogle Scholar
  71. 71.
    Armour JA, Linderoth B, Arora RC, et al. Long-term modulation of the intrinsic cardiac nervous system by spinal cord neurons in normal and ischaemic hearts. Auton Neurosci. 2002;95:71–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Cardinal R, Ardell JL, Linderoth B, Vermeulen M, Foreman RD, Armour JA. Spinal cord activation differentially modulates ischaemic electrical responses to different stressors in canine ventricles. Auton Neurosci. 2004;111:37–47.PubMedCrossRefGoogle Scholar
  73. 73.
    Issa ZF, Zhou X, Ujhelyi MR, et al. Thoracic spinal cord stimulation reduces the risk of ischemic ventricular arrhythmias in a postinfarction heart failure canine model. Circulation. 2005;111:3217–20.PubMedCrossRefGoogle Scholar
  74. 74.
    Liu Y, Yue WS, Liao SY, et al. Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure. J Cardiovasc Electrophysiol. 2012;23:534–40.PubMedCrossRefGoogle Scholar
  75. 75.
    Zipes DP, Neuzil P, Theres H, et al. Ventricular functional response to spinal cord stimulation of advanced heart failure: primary results of the randomized DEFEAT-HF trial. Paper presented at: American Heart Association. Chicago; 2014.Google Scholar
  76. 76.
    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.CrossRefGoogle Scholar
  77. 77.
    Zhang D, Liu J, Zheng H, Tu H, Muelleman RL, Li YL. Effect of angiotension II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats. J Hypertens 2015;33(7):1401–10.Google Scholar
  78. 78.
    Nolan J, Batin PD, Andrews R, et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation. 1998;98:1510–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Schwartz PJ, La Rovere MT, Vanoli E. Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation. 1992;85:I77–91.PubMedGoogle Scholar
  80. 80.
    Sata Y, Kawada T, Shimizu S, Kamiya A, Akiyama T, Sugimachi M. Predominant role of neural arc in sympathetic baroreflex resetting of spontaneously hypertensive rats. Circ J Off J Japan Circ Soc. 2015;79:592–9.Google Scholar
  81. 81.
    Marcus NJ, Del Rio R, Schultz EP, Xia XH, Schultz HD. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure. J Physiol. 2014;592:391–408.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Braunwald NS, Epstein SE, Braunwald E. Carotid sinus nerve stimulation for the treatment of intractable angina pectoris: surgical technic. Ann Surg. 1970;172:870–6.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Sabbah HN, Gupta RC, Imai M, et al. Chronic electrical stimulation of the carotid sinus baroreflex improves left ventricular function and promotes reversal of ventricular remodeling in dogs with advanced heart failure. Circ Heart Fail. 2011;4:65–70.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Zucker IH, Hackley JF, Cornish KG, et al. Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure. Hypertension. 2007;50:904–10.PubMedCrossRefGoogle Scholar
  85. 85.
    Scheffers IJ, Kroon AA, Schmidli J, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56:1254–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Bisognano JD, Kaufman CL, Bach DS, et al. Improved cardiac structure and function with chronic treatment using an implantable device in resistant hypertension: results from European and United States trials of the Rheos system. J Am Coll Cardiol 2011;57:1787–1788.Google Scholar
  87. 87.
    Bisognano JD, Bakris G, Nadim MK, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58:765–73.PubMedCrossRefGoogle Scholar
  88. 88.
    Abraham WT, Zile M, Weaver FA, et al. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC Heart Fail. 2015; in press.Google Scholar
  89. 89.
    Villarreal D, Freeman RH, Johnson RA, Simmons JC. Effects of renal denervation on postprandial sodium excretion in experimental heart failure. Am J Physiol. 1994;266:R1599–604.PubMedGoogle Scholar
  90. 90.
    Nozawa T, Igawa A, Fujii N, et al. Effects of long-term renal sympathetic denervation on heart failure after myocardial infarction in rats. Heart Vessel. 2002;16:51–6.CrossRefGoogle Scholar
  91. 91.
    Clayton SC, Haack KK, Zucker IH. Renal denervation modulates angiotensin receptor expression in the renal cortex of rabbits with chronic heart failure. Am J Physiol Renal Physiol. 2011;300:F31–9.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Zhao Q, Huang H, Wang X, et al. Changes of serum neurohormone after renal sympathetic denervation in dogs with pacing-induced heart failure. Int J Clin Exp Med. 2014;7:4024–30.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Dai Z, Yu S, Zhao Q, et al. Renal sympathetic denervation suppresses ventricular substrate remodelling in a canine high-rate pacing model. EuroIntervention J EuroPCR Collab Work Group Int Cardiol Eur Soc Cardiol. 2014;10:392–9.Google Scholar
  94. 94.
    Guo Z, Zhao Q, Deng H, et al. Renal sympathetic denervation attenuates the ventricular substrate and electrophysiological remodeling in dogs with pacing-induced heart failure. Int J Cardiol. 2014;175:185–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Bradfield JS, Vaseghi M, Shivkumar K. Renal denervation for refractory ventricular arrhythmias. Trends Cardiovasc Med. 2014;24:206–13.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Remo BF, Preminger M, Bradfield J, et al. Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy. Heart Rhythm Off J Heart Rhythm Soc. 2014;11:541–6.CrossRefGoogle Scholar
  97. 97.
    Brandt MC, Mahfoud F, Reda S, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59:901–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Davies JE, Manisty CH, Petraco R, et al. First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study. Int J Cardiol. 2013;162:189–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Una Buckley
    • 1
    • 4
  • Kalyanam Shivkumar
    • 1
    • 3
  • Jeffrey L. Ardell
    • 1
    • 2
    Email author
  1. 1.Cardiac Arrhythmia Center & Neurocardiology Research Center of ExcellenceUCLA David Geffen School of MedicineLos AngelesUSA
  2. 2.Department of Medicine (Cardiology)UCLA Health SystemLos AngelesUSA
  3. 3.Interventional Cardiovascular ProgramsUCLA Health SystemLos AngelesUSA
  4. 4.UCLA Cardiac Arrhythmia CenterUCLA Health SystemLos AngelesUSA

Personalised recommendations