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Resistant hypertension carries an increased risk of end-organ damage and cardiovascular events, as compared to controllable hypertension. This review will focus on carotid baroreceptor stimulation as a means to correct it.
Resistant hypertension occurs when 1) use of at least three antihypertensive drugs at full daily dosage - of which a diuretic- are unsuccessful in controlling blood pressure, and, having excluded pseudoresistance (white coat phenomenon), 2) contributing factors such as certain exogenous substances, or secondary causes of hypertension including hyperaldosteronism, obstructive sleep apnea, parenchymal and vascular kidney disease, pheochromocytoma, are possibly at work. Hypertension is resistant in 15-30% of study subjects and is often uncontrolled because of persistently elevated and isolated systolic hypertension. It is characterised by an excess in aldosterone and an increased intravascular volume. Renal sympathetic hyperactivity can cause hypertension to be maintained and even progress as the kidney is a source of central sympathetic outflow via renal nerve activity.Pathophysiology of kidney function and interaction between the kidney and the brain, justifies the use of renal sympathetic denervation in the treatment of resistant hypertension and recent trials have corroborated this. (1-3) Previously in the e-journal, were published a review of the role of renal sympathetic nerves and denervation by Prof Tendera, on identification and management of resistant hypertension by Prof. Ruilope, as well as the initial clinical reports on denervation by Prof. Clement.
Recently an implantable device to electrically stimulate the carotid baroreceptors, to decrease sympathetic outflow (4), was used, and may have benefits in BP reduction in conditions with sympathetic nervous system predominance such as obesity (5), obstructive sleep apnoea (6), and isolated systolic hypertension (7). The electrical stimulation of carotid baroreceptors is a noninvasive procedure achieved by:
Blood pressure is lowered through sympathetic inhibition: the activation energy given from the device is conducted through the carotid leads to the carotid baroreceptors, which send signals to the brain, interpreted as a blood pressure rise; the brain sends signals to vessels, heart and kidneys to reduce blood pressure (8-10). The implanting of carotid electrodes in the perivascular space around the carotid sinus minimises effects on carotid chemoreceptors and reduces the damage to the carotid baroreceptor by avoiding dissection in the carotid bifurcation, therefore with no side effects. In addition, it has been shown that the chronic stimulation of the carotid baroreceptors does not cause injury, remodelling, or stenosis of the carotid arteries (11-12).For proper placement of the electrodes a team of specialists hypertension, surgeons, anesthetists, and technicians, are needed as well as 1 to 2 days of hospital stay; antihypertensive drugs are withheld on the day of implantation, except for β-blockers.Clinical trials on carotid receptor stimulation by an implantable device showed a significant reduction in both office systolic (22 or 34 mmHg) and diastolic (18 or 20 mmHg) blood pressure, 24-hour ambulatory blood pressure (14/9 mmHg), and heart rate (12 bpm), which was evident from study onset and was maintained at follow-up. Available data suggest a beneficial effect of carotid baroreceptor stimulation on the reversal of left ventricular hypertrophy and cardiac structure and function, with attenuated mitral A-valve velocity and reduced left atrial dimensions; also carotid baropacing does not impair the renal function of patients with resistant hypertension, even during prolonged follow-up periods (13-18).
Recently the implantation of a permanent bilateral perivascular carotid sinus pulse generator for carotid baroreceptor stimulation was used, causing sustained blood pressure and heart rate reduction, in patients with resistant hypertension.Further clinical studies including large numbers of patients and detailed data on the long-term effects of the procedure are needed, to verify safety and efficacy of this new therapeutic approach.
1.Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Symplicity HTN-1 Investigators. Hypertension. 2011 May;57(5):911-7. Epub 2011 Mar 14.2.Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial.Symplicity HTN-2 Investigators. The Lancet, Vol 376, Issue 9756, Pages 1903 - 1909, 4 December 2010. 3.Renal Sympathetic Denervation for the Treatment of Difficult-to-Control or Resistant Hypertension. Papademetriou V, Doumas M, Tsioufis K. Int J Hypertens. 2011;2011:196518. Epub 2011 Mar 30. 4.Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients.Heusser K, Tank J, Engeli S, et al. Hypertension 2010; 55: 619–626. 5.Prolonged activation of the baroreflex abolishes obesity-induced hypertension.Lohmeier TE, Dwyer TM, Irwin ED, et al. Hypertension 2007, 49:1307–1314. 6.Sympathetic nerve activity in obstructive sleep apnoea.Narkiewicz K, Somers VK. Acta Physiol Scand. 2003 Mar;177(3):385-90. 7.Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly.Grassi G, Seravalle G, Bertinieri G, et al. J Hypertens 2000; 18: 587–593. 8.Baroreflex device therapy in the treatment of hypertension.Uppuluri SC, Storozynsky E, Bisognano JD. Curr Hypertens Rep 2009, 11:69–75. 9.Cardiovascular effects of direct stimulation of the carotid sinus nerve in man.Carlsten A, Folkow B, Grimby G, et al. Acta Physiol Scand 1958, 44:138–145. 10.Recent insights into the interactions between the baroreflex and the kidneys in hypertension.Lohmeier TE, Hildebrandt DA, Warren S, et al.Am J Physiol Regul Integr Comp Physiol 2005, 288:R828–R836. 11.An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multicenter feasibility trial for the treatment of resistant hypertension.Tordoir JHM, Scheffers I, Schmidli J, et al.: Eur J Vasc Endovasc Surg 2007, 33:414–421. 12.Implantable carotid sinus stimulator for the treatment of resistant hypertension: local effects on carotid artery morphology.Sanchez LA, Illig K, Levy M, Trachiotis G, Shanley C, Irwin E, Jim J, Rossing M, Kieval R. Ann Vasc Surg. 2010 Feb;24(2):178-84. doi: 10.1016/j.avsg.2009.10.003. Epub 2009 Dec 29. 13.Prolonged activation of the baroreflex produces sustained hypotension. Hypertension 2004, 43:306–311.Lohmeier TE, Irwin E, Rossing M, et al.: 14.An implantable carotid sinus stimulator for drug resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos Feasibility Trial.Illig KA, Levy M, Sanchez L, et al.: J Vasc Surg 2006, 44:1213–1218. 15.An implantable carotid sinus baroreflex activating system for drug-resistant hypertension: interim chronic efficacy results from the multicenter Rheos Feasibility Trial.Bisognano J, Sloand J, Papademetriou V, et al.Circulation 2006, 114(18 Suppl):II575. 16.Sustained blood pressure reduction by baroreflex hypertension therapy with a chronically implanted system: 2-year data from the Rheos DEBuT-HT study in patients with resistant hypertension.Scheffers I, Schmidli J, Kroon AA, et al.: J Hypertens 2008, 26(Suppl I):S19. 17.Sustained blood pressure reduction by baroreflex hypertension therapy with a chronically implanted system: 3-year data from the Rheos DEBuT study in patients with resistant hypertension.Scheffers I, Schmidli J, Kroon AA, et al.: J Hypertens 2009, 27(Suppl 4):S421. 18.The DEBuT and Rheos Feasibility Investigators: Chronic treatment of resistant hypertension with an implantable device: interim 2 year results of two studies of the Rheos hypertension system.Rothstein M, de Leeuw P, Elletson M; [abstract]. Presented at the American College of Cardiology 58th Annual Scientific Session. Orlando, FL; March 29–31, 2009.
Authors:1§Eugenio Greco – 2Raffaella Greco1ASP N° 1 - Cosenza - ITALY. §FESC 2Hematology and BMT Unit - Scientific Institute Ospedale San Raffaele - Milan – ITALYCorrespondence to: Eugenio Greco, MD, PhD, FESC Web sites: http://eugenio.greco.docvadis.it - http://www.medicitalia.it/grecoeugenioAuthors' disclosures: None declared.