Interventional Treatment of Hypertension: A New Paradigm

  • W. Schuyler Jones
  • Sreekanth Vemulapalli
  • Manesh R. Patel
Interventional Cardiology (S Rao, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Interventional Cardiology


Hypertension is thought to contribute to more than 7 million deaths worldwide each year and contributes to the development of atherosclerotic lesions that lead to myocardial infarction and stroke. While lifestyle modifications (diet, exercise, weight loss) and pharmacotherapy have been proven to be effective in the treatment of hypertension, as many as half of patients have uncontrolled BP and remain at risk for elevated cardiovascular morbidity and mortality. The main physiologic targets for interventional treatment include alteration of blood flow to the kidney, activation of the carotid baroreflex system, and modification of the renal sympathetic nervous system. The results of prior studies and new studies of interventional treatments of resistant hypertension are covered in this review.


Hypertension Resistant hypertension Baroreceptor activation therapy Renal artery stenosis Renal sympathetic denervation 



Duke University is a clinical site involved in enrollment of patients in SYMPLICITY HTN-3. As such, Duke receives research money to participate. All 3 of the authors are site investigators but do not receive salary or other compensation for this project.

Conflict of Interest

W.S. Jones declares that he has no conflict of interest.

S. Vemulapalli has received grant support from Medtronic for a peripheral vascular disease fellowship grant. He has also received travel/accommodations expenses covered or reimbursed from Medtronic for travel costs for SYMPLICITY HTN-3 investigators meeting.

M.R. Patel has been a consultant for Genzyme, Baxter, Jensen, and Bayer. He has received grant support from AstraZeneca, Johnson & Johnson, and Maquet.


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

  1. 1.
    Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents. Circulation. 2011;123:2434–506.PubMedCrossRefGoogle Scholar
  2. 2.
    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;42:1206–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL, et al. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association council for high blood pressure research and the councils on clinical cardiology and epidemiology and prevention. Circulation. 2007;115:2761–88.PubMedCrossRefGoogle Scholar
  4. 4.
    Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. J Am Med Assoc. 2003;290:199–206.CrossRefGoogle Scholar
  5. 5.
    Global Health Risks, World Health Organization, 2009. Accessed 7 Nov 2012.
  6. 6.
    Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–26.PubMedCrossRefGoogle Scholar
  7. 7.
    Sarafidis PA, Bakris GL. Resistant hypertension. An overview of evaluation and treatment. J Am Coll Cardiol. 2008;52:1749–57.PubMedCrossRefGoogle Scholar
  8. 8.
    Moser M, Setaro JF. Resistant or difficult-to-control hypertension. N Engl J Med. 2006;355:385–92.PubMedCrossRefGoogle Scholar
  9. 9.
    • 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;125:1635–42. This community cohort study is a nice descriptive analysis of resistant hypertension and outcomes in these patients.PubMedCrossRefGoogle Scholar
  10. 10.
    Parati G, Esler M. The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J. 2012;33:1058–66.PubMedCrossRefGoogle Scholar
  11. 11.
    Olin JY, Melia M, Young JR, Graor RA, Risius B. Prevalence of atherosclerotic renal artery stenosis in patients with atherosclerosis elsewhere. Am J Med. 1990;88:46N–51N.PubMedCrossRefGoogle Scholar
  12. 12.
    Rimmer JM, Gennari FJ. Atherosclerotic renovascular disease and progressive renal failure. Ann Intern Med. 1993;118:712–9.PubMedCrossRefGoogle Scholar
  13. 13.
    The ASTRAL Investigators. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009;361:1953–62.CrossRefGoogle Scholar
  14. 14.
    White CJ. Kiss my astral: one seriously flawed study of renal stenting after another. Catheter Cardiovasc Interv. 2010;75:305–7.PubMedCrossRefGoogle Scholar
  15. 15.
    White CJ. Management of renal artery stenosis: the case for intervention, defending current guidelines, and screening (Drive By) renal angiography at the time of catheterization. Prog Card Dis. 2009;52:229–37.CrossRefGoogle Scholar
  16. 16.
    • Kumbhani DJ, Bavry AA, Harvey JE, de Souza R, Scarpioni R, Bhatt DL, et al. Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: a meta-analysis of randomized controlled trials. Am Heart J. 2011;161:622–30. This is the most updated meta-analysis on treatment of hypertension with renal artery revascularization.PubMedCrossRefGoogle Scholar
  17. 17.
    • Jaff MR, Bates M, Sullivan T, Popma J, Gao X, Zaugg M, et al. Significant reduction in systolic blood pressure following renal artery stenting in patients with uncontrolled hypertension: results from the HERCULES trial. Catheter Cardiovasc Interv. 2012;80:343–50. A single-arm study of renal artery stenting in selected population of uncontrolled hypertensive patients.PubMedCrossRefGoogle Scholar
  18. 18.
    Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Guidelines for the Management of Patients with Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): a Collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). J Am Coll Cardiol. 2006;47:e1–e192.CrossRefGoogle Scholar
  19. 19.
    Schwartz SI, Griffith LSC, Neistadt A, Hagfors N. Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg. 1967;114:5–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Wustmann K, Kucera JP, Scheffers I, Mohaupt M, Kroon AA, de Leeux PW, et al. Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension. Hypertension. 2009;54:530–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Heusser K, Tank J, Engeli S, Diedrich A, Menne J, Eckert S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55:619–26.PubMedCrossRefGoogle Scholar
  22. 22.
    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;44:1213–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Scheffers IJM, 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;56:1254–8.PubMedCrossRefGoogle Scholar
  24. 24.
    •• 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. J Am Coll Cardiol. 2011;58:765–73. The largest study of baroreflex activation therapy published to date.PubMedCrossRefGoogle Scholar
  25. 25.
    Bakris GL, Nadim MK, Haller H, Lovett EG, Schafer JE, Bisognano JD, et al. 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;6:152–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Freyberg RH, Peet MM. The effect on the kidney of bilateral splanchnicectomy in patients with hypertension. J Clin Invest. 1937;16:49–65.PubMedCrossRefGoogle Scholar
  27. 27.
    Isberg EM, Peet MM. The influence of supradiaphragmatic splanchnicectomy on the heart in hypertension. Am Heart J. 1948;35:567–83.PubMedCrossRefGoogle Scholar
  28. 28.
    Smithwick RH. Surgical treatment of hypertension. Am J Med. 1948;4:744–59.PubMedCrossRefGoogle Scholar
  29. 29.
    Smithwick RH, Bush RD, Kinsey D, Whitelaw GP. Hypertension and associated cardiovascular disease; comparison of male and female mortality rates and their influence on selection of therapy. J Am Med Assoc. 1956;160:1023–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicenter safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81.PubMedCrossRefGoogle Scholar
  31. 31.
    • Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011;57:911–7. The first study to show that renal sympathetic denervation is associated with long-term blood pressure reduction. Google Scholar
  32. 32.
    •• Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomized controlled trial. Lancet. 2010;376:1903–9. This study reported the safety and effectiveness of renal sympathetic denervation when compared with control in resistant hypertension. Google Scholar
  33. 33.
    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;58:1176–82.PubMedCrossRefGoogle Scholar
  34. 34.
    Geisler BP, Egan BM, Cohen JT, Garner AM, Akehurst RL, Esler MD, et al. Cost-effectiveness and clinical effectiveness of catheter-based renal denervation for resistant hypertension. J Am Coll Cardiol. 2012;60:1271–7.PubMedCrossRefGoogle Scholar
  35. 35.
    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;35:528–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Brandt MC, Reda S, Mahfoud F, Lenski M, Böhm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Am Coll Cardiol. 2012;60:1956–65.PubMedCrossRefGoogle Scholar
  37. 37.
    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;59:901–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B, et al. Effects of Renal Sympathetic Denervation on Heart Rate and Atrioventricular Conduction in Patients with Resistant Hypertension. Int J Cardiol 2012 [epub ahead of print].Google Scholar
  39. 39.
    Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of sympathetic denervation on glucose metabolism in patients with resistant hypertension. Circulation. 2011;123:1940–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Prochnau D, Lucas N, Kuehnert H, Figulla HR, Surber R. Catheter-based renal denervation for drug-resistant hypertension by using a standard electrophysiology catheter. Eurointervention. 2012;7:1077–80.PubMedCrossRefGoogle Scholar
  41. 41.
    Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. Eurointervention. 2012;8:57–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Ormiston J, Watson T, van Pelt N, Stewart R, Haworth P, Stewart JT, et al. First report of the 6-month first in human results of the OneShot renal denervation system: the RHAS Study [Abstract TCT-212]. Presented at Transcatheter Cardiovascular Therapeutics Conference. Miami, Florida, USA; October 22–26, 2012.Google Scholar
  43. 43.
    Worthley S, Tsioufis C, Worthley M, Sinhal A, Chew D, Meredith I, et al. Safety and efficacy of a novel multi-electrode renal denervation catheter in resistant hypertension: 3 month data from the EnligHTN I Trial. [Abstract TCT-213]. Presented at Transcatheter Cardiovascular Therapeutics Conference. Miami, Florida, USA; October 22–26, 2012.Google Scholar
  44. 44.
    Doumas M, Faselis C, Papdemetriou V. Renal sympathetic denervation and systemic hypertension. Am J Cardiol. 2010;105:570–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • W. Schuyler Jones
    • 1
    • 2
  • Sreekanth Vemulapalli
    • 2
  • Manesh R. Patel
    • 1
    • 2
  1. 1.Duke Clinical Research InstituteDuke University Medical CenterDurhamUSA
  2. 2.Division of CardiologyDuke University Medical CenterDurhamUSA

Personalised recommendations