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Renal Denervation Therapy and Baroreceptor Activation Therapy: Emerging Tools for Treating Resistant Hypertension

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Hypertension in High Risk African Americans

Part of the book series: Clinical Hypertension and Vascular Diseases ((CHVD))

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Abstract

Despite the availability of over 125 approved different antihypertensive medications, a sizeable 36 million (48 %) of the 75 million people with hypertension in the USA are not achieving guideline blood pressure goals known to reduce cardiovascular morbidity and mortality and kidney disease progression. Between 3 and 6 % of these 75 million, hypertensives are estimated to have resistant hypertension. A major contributing factor for poor blood pressure control is failure of antihypertensive agents to inhibit the sympathetic nervous system adequately. Consequently, alternative approaches using devices have been developed. Recent technical advances targeting the renal sympathetic nerves, i.e., renal denervation therapy (RDT), and the baroreceptors in the carotid sinuses, i.e., baroreflex activation therapy (BAT), have been the focus of more invasive therapies to treat resistant hypertension. Encouraging results from the Symplicity HTN-2 and Rheos Pivotal trials on efficacy and safety of RDT and BAT indicate these therapies can safely reduce blood pressure in patients with resistant hypertension. These approaches, while some are approved in other parts of the world, i.e., RDT, are still experimental in the USA and the results of these ongoing clinical trials will determine their approval.

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References

  1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52.

    Article  CAS  PubMed  Google Scholar 

  2. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment. Hypertension. 2008;51(6):1403–19.

    Article  CAS  PubMed  Google Scholar 

  3. Doumas M, et al. Benefits from treatment and control of patients with resistant hypertension. Int J Hypertens. 2010;2011:318549.

    PubMed Central  PubMed  Google Scholar 

  4. Roberie DR, Elliott WJ. What is the prevalence of resistant hypertension in the United States? Curr Opin Cardiol. 2012;27(4):386–91.

    Article  PubMed  Google Scholar 

  5. Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011;124(9):1046–58.

    Article  PubMed Central  PubMed  Google Scholar 

  6. McAdam-Marx C, Ye X, Sung JC, Brixner DI, Kahler KH. Results of a retrospective, observational pilot study using electronic medical records to assess the prevalence and characteristics of patients with resistant hypertension in an ambulatory care setting. Clin Ther. 2009;31(5):1116–23.

    Article  PubMed  Google Scholar 

  7. Sarafidis P. Resistant hypertension—its identification and epidemiology. Nat Rev Nephrol. 2013;9:51–8.

    Article  PubMed  Google Scholar 

  8. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.

    Article  PubMed  Google Scholar 

  9. Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996;334(1):13–8.

    Article  CAS  PubMed  Google Scholar 

  10. Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension. 2011;57(6):1076–80.

    Article  CAS  PubMed  Google Scholar 

  11. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125(13):1635–42.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Gupta AK, Nasothimiou EG, Chang CL, Sever PS, Dahlof B, Poulter NR, et al. Baseline predictors of resistant hypertension in the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT): a risk score to identify those at high-risk. J Hypertens. 2011;29(10):2004–13.

    Article  CAS  PubMed  Google Scholar 

  13. de la Sierra A, Segura J, Banegas JR, Gorostidi M, de la Cruz JJ, Armario P, et al. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension. 2011;57(5):898–902.

    Article  PubMed  Google Scholar 

  14. de la Sierra A, Banegas JR, Oliveras A, Gorostidi M, Segura J, de la Cruz JJ, et al. Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs. J Hypertens. 2012;30(6):1211–6.

    Article  PubMed  Google Scholar 

  15. Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52(22):1749–57.

    Article  PubMed  Google Scholar 

  16. Collins R, Peto R, MacMahon S, Godwin J, Qizilbash N, Hebert P, et al. Blood pressure, stroke, and coronary heart disease. Lancet. 1990;335(8693):827–38.

    Article  CAS  PubMed  Google Scholar 

  17. Briasoulis A, Bakris G. Timing and efficacy of alternative methods of sympathetic blockade. Curr Hypertens Rep. 2012;14(5):455–61.

    Article  CAS  PubMed  Google Scholar 

  18. DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75–197.

    CAS  PubMed  Google Scholar 

  19. Esler M. The sympathetic nervous system through the ages: from Thomas Willis to resistant hypertension. Exp Physiol. 2011;96(7):611–22.

    PubMed  Google Scholar 

  20. Barajas L, Powers K, Wang P. Innervation of the renal cortical tubules: a quantitative study. Am J Physiol. 1984;247(1):F50–60.

    CAS  PubMed  Google Scholar 

  21. DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R245–53.

    Article  CAS  PubMed  Google Scholar 

  22. Wyss JM, Carlson S. The role of the central nervous system in hypertension. Curr Hypertens Rep. 1999;1(3):246–53.

    Article  CAS  PubMed  Google Scholar 

  23. Roman RJ, Cowley AW. Characterization of a new model for the study of pressure-natriuresis in the rat. Am J Physiol. 1985;248(2):F190–8.

    CAS  PubMed  Google Scholar 

  24. Corry D, Tuck M. Obesity, hypertension, and sympathetic nervous system activity. Curr Hypertens Rep. 1999;1(2):119–26.

    Article  CAS  PubMed  Google Scholar 

  25. Eslami P, Tuck M. The role of the sympathetic nervous system in linking obesity with hypertension in white versus black Americans. Curr Hypertens Rep. 2003;5(3):269–72.

    Article  PubMed  Google Scholar 

  26. Abate NI, Mansour YH, Tuncel M, Arbique D, Chavoshan B, Kizilbash A, et al. Overweight and sympathetic overactivity in black Americans. Hypertension. 2001;38(3):379–83.

    Article  CAS  PubMed  Google Scholar 

  27. Smithwick Rh TJE. Splanchnicectomy for essential hypertension: results in 1,266 cases. JAMA. 1953;152(16):1501–4.

    Article  Google Scholar 

  28. Morrissey DM, Brookes V, Cooke WT. Sympathectomy in the treatment of hypertension: review of 122 cases. Lancet. 1953;261(6757):403–8.

    Article  Google Scholar 

  29. Newcombe CP, Shucksmith HS, Suffern WS. Sympathectomy for hypertension; follow-up of 212 patients. Br Med J. 1959;1(5115):142–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Peet Mm IE. The surgical treatment of arterial hypertension. JAMA. 1946;130(8):467–73.

    Article  Google Scholar 

  31. Evelyn KA, Singh MM, Chapman WP, Perera GA, Thaler H. Effect of thoracolumbar sympathectomy on the clinical course of primary (essential) hypertension. A ten-year study of 100 sympathectomized patients compared with individually matched, symptomatically treated control subjects. Am J Med. 1960;28:188–221.

    Article  CAS  PubMed  Google Scholar 

  32. Bertog SC, Sobotka PA, Sievert H. Renal denervation for hypertension. JACC Cardiovasc Interv. 2012;5(3):249–58.

    Article  PubMed  Google Scholar 

  33. Kandzari DE, Bhatt DL, Sobotka PA, O’Neill WW, Esler M, Flack JM, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial. Clin Cardiol. 2012;35(9):528–35.

    Article  PubMed  Google Scholar 

  34. Prochnau D. Catheter-based renal denervation for drug-resistant hypertension by using a standard electrophysiology catheter. EuroIntervention. 2012;7(9):1077–80.

    Article  PubMed  Google Scholar 

  35. Prochnau D, Figulla HR, Surber R. Efficacy of renal denervation with a standard EP catheter in the 24-h ambulatory blood pressure monitoring and long-term follow-up. Int J Cardiol. 2012;157(3):447–8.

    Article  PubMed  Google Scholar 

  36. Worthley SG, Tsioufis CP, Worthley MI, Sinhal A, Chew DP, Meredith IT, et al. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial. Eur Heart J. 2013;34(28):2132–40.

    Google Scholar 

  37. Bunte MC, Infante de Oliveira E, Shishehbor MH. Endovascular treatment of resistant and uncontrolled hypertension: therapies on the horizon. JACC Cardiovasc Interv. 2013;6(1):1–9.

    Article  PubMed  Google Scholar 

  38. Ukena C, Mahfoud F, Kindermann I, Barth C, Lenski M, Kindermann M, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol. 2011;58(11):1176–82.

    Article  PubMed  Google Scholar 

  39. Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376(9756):1903–9.

    Google Scholar 

  40. Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension : durability of blood pressure reduction out to 24 months. Hypertension. 2011;57(5):911–7.

    Google Scholar 

  41. Mabin T. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroIntervention. 2012;8(1):57–61.

    Article  PubMed  Google Scholar 

  42. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275–81.

    Article  PubMed  Google Scholar 

  43. Gosain P, Garimella PS, Hart PD, Agarwal R. Renal sympathetic denervation for treatment of resistant hypertension: a systematic review. J Clin Hypertens (Greenwich). 2013;15(1):75–84.

    Article  Google Scholar 

  44. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Böhm 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.

    Article  PubMed  Google Scholar 

  45. Witkowski A, Prejbisz A, Florczak E, Kądziela J, Śliwiński P, Bieleń P, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58(4):559–65.

    Article  CAS  PubMed  Google Scholar 

  46. Simonetti G, Spinelli A, Gandini R, Da Ros V, Gaspari E, Coco I, et al. Endovascular radiofrequency renal denervation in treating refractory arterial hypertension: a preliminary experience. Radiol Med. 2012;117(3):426–44.

    Article  CAS  PubMed  Google Scholar 

  47. Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension. Circulation. 2011;123(18):1940–6.

    Article  CAS  PubMed  Google Scholar 

  48. Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C, et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;23(7):1250–7.

    Google Scholar 

  49. Voskuil M, Verloop W, Blankestijn P, Agostoni P, Stella P, Doevendans P. Percutaneous renal denervation for the treatment of resistant essential hypertension; the first Dutch experience. Neth Heart J. 2011;19(7):319–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Lambert GW, Hering D, Esler MD, Marusic P, Lambert EA, Tanamas SK, et al. Health-related quality of life after renal denervation in patients with treatment-resistant hypertension. Hypertension. 2012;60(6):1479–84.

    Article  CAS  PubMed  Google Scholar 

  51. Vase H, et al. Catheter-based renal denervation for treatment of resistant hypertension. Dan Med J. 2012;59(6):A4439.

    PubMed  Google Scholar 

  52. Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23:1250–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Lohmeier TE, Hildebrandt DA, Warren S, May PJ, Cunningham JT. Recent insights into the interactions between the baroreflex and the kidneys in hypertension. Am J Physiol Regul Integr Comp Physiol. 2005;288(4):R828–36.

    Article  CAS  PubMed  Google Scholar 

  54. McCubbin JW, Green JH, Page IH. Baroceptor function in chronic renal hypertension. Circ Res. 1956;4(2):205–10.

    Article  CAS  PubMed  Google Scholar 

  55. Chapleau MW, Hajduczok G, Abboud FM. Mechanisms of resetting of arterial baroreceptors: an overview. Am J Med Sci. 1988;295(4):327–34.

    Article  CAS  PubMed  Google Scholar 

  56. Lohmeier TE, Dwyer TM, Irwin ED, Rossing MA, Kieval RS. Prolonged activation of the baroreflex abolishes obesity-induced hypertension. Hypertension. 2007;49(6):1307–14.

    Article  CAS  PubMed  Google Scholar 

  57. Lohmeier TE, Iliescu R, Dwyer TM, Irwin ED, Cates AW, Rossing MA. Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am J Physiol Heart Circ Physiol. 2010;299(2):H402–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation: mechanisms and potential for hypertension therapy. Hypertension. 2011;57(5):880–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Lohmeier TE, Dwyer TM, Hildebrandt DA, Irwin ED, Rossing MA, Serdar DJ, et al. Influence of prolonged baroreflex activation on arterial pressure in angiotensin hypertension. Hypertension. 2005;46(5):1194–200.

    Article  CAS  PubMed  Google Scholar 

  60. Iliescu R, Irwin ED, Georgakopoulos D, Lohmeier TE. Renal responses to chronic suppression of central sympathetic outflow. Hypertension. 2012;60(3):749–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Lohmeier TE, Iliescu R. Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation. J Appl Physiol. 2012;113(10):1652–8.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Carlsten A, Folkow B, Grimby G, Hamberger CA, Thulesius O. Cardiovascular effects of direct stimulation of the carotid sinus nerve in man. Acta Physiol Scand. 1958;44(2):138–45.

    Article  CAS  PubMed  Google Scholar 

  63. Bilgutay AM, Lillehei CW. Treatment of Hypertension with an Implantable electronic device. JAMA. 1965;191:649–53.

    Article  CAS  PubMed  Google Scholar 

  64. Schwartz SI, Griffith LS, Neistadt A, Hagfors N. Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg. 1967;114(1):5–15.

    Article  CAS  PubMed  Google Scholar 

  65. Navaneethan SD, Lohmeier TE, Bisognano JD. Baroreflex stimulation: a novel treatment option for resistant hypertension. J Am Soc Hypertens. 2009;3(1):69–74.

    Article  PubMed  Google Scholar 

  66. Illig KA, Levy M, Sanchez L, Trachiotis GD, Shanley C, Irwin E, et al. An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg. 2006;44(6):1213–8.

    Article  PubMed  Google Scholar 

  67. Bisognano J. An implantable carotid sinus baroreflex activating system for drug-resistant hypertension: interim chronic efficacy results from the multi-center Rheos Feasibility Trial. Circulation. 2006;114:575.

    Article  Google Scholar 

  68. Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56(15):1254–8.

    Article  PubMed  Google Scholar 

  69. Wustmann K, Kucera JP, Scheffers I, Mohaupt M, Kroon AA, de Leeuw PW, et al. Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension. Hypertension. 2009;54(3):530–6.

    Article  CAS  PubMed  Google Scholar 

  70. Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J, 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(7):765–73.

    Article  PubMed  Google Scholar 

  71. Bakris GL, Nadim MK, Haller H, Lovett EG, Schafer JE, Bisognano JD. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. 2012;6(2):152–8.

    Article  PubMed  Google Scholar 

  72. Alnima T, de Leeuw P, Tan F, Kroon A, Rheos Pivotal Trial Investigators. Renal responses to long term carotid baroreflex activation in patients with drug resistant hypertension. Hypertension. 2013;61(6):1334–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL, USA

    Peter D. Hart

  2. Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL, USA

    Peter D. Hart & Priyanka Gosain

  3. Department of Medicine, ASH Comprehensive Hypertension Center, The University of Chicago Medicine, 5841 S. Maryland Avenue, MC 1027, Chicago, IL, 60637, USA

    George Bakris M.D.

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  1. Peter D. Hart
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  2. Priyanka Gosain
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  3. George Bakris M.D.
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Correspondence to George Bakris M.D. .

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  1. Cardiology, Tulane University School of Medicine, New Orleans, Louisiana, USA

    Keith C. Ferdinand

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Hart, P.D., Gosain, P., Bakris, G. (2015). Renal Denervation Therapy and Baroreceptor Activation Therapy: Emerging Tools for Treating Resistant Hypertension. In: Ferdinand, K. (eds) Hypertension in High Risk African Americans. Clinical Hypertension and Vascular Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2010-5_11

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  • DOI: https://doi.org/10.1007/978-1-4939-2010-5_11

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