Renal sympathetic denervation

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Renal sympathetic denervation
Other namesRenal denervation

Renal sympathetic denervation (RSDN) is a minimally invasive, endovascular catheter based procedure using radiofrequency ablation or ultrasound ablation aimed at treating resistant hypertension (high blood pressure not controlled by medication). [1] Nerves in the wall of the renal artery are ablated by applying radiofrequency pulses or ultrasound to the renal arteries. This causes reduction of sympathetic afferent and efferent activity to the kidney and blood pressure can be decreased. [2] Early data from international clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension. [2] [3] However, in 2014 a prospective, single-blind, randomized, sham-controlled clinical trial failed to confirm a beneficial effect on blood pressure. [4] A 2014 consensus statement from The Joint UK Societies did not recommend the use of renal denervation for treatment of resistant hypertension on current evidence. [5] More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure. [6] [7] [8]

Contents

History

Prior to pharmacological management of hypertension, surgical sympathectomy was a recognized treatment for hypertension. [9] This was often successful in reducing blood pressure but due to its non-selective nature the side effects of the procedure were poorly tolerated. Side effects included orthostatic hypotension, palpitations, anhydrosis, intestinal disturbances, loss of ejaculation, thoracic duct injuries and atelectasis. [10] Modern antihypertensive pharmacological interventions have improved the control of hypertension, but only 34–66% of people with hypertension in England, US and Canada have blood pressure at or below target levels. [11] Resistant hypertension is defined as blood pressure above target (140/90mm Hg) despite concomitant use of three or more anti-hypertensives – one of which should be a diuretic. [12] It has been estimated that 8–10% of people with hypertension fall into this category. [5]

Devices

Several commercial devices exist. [13] These include Medtronic's Symplicity Renal Denervation System, St. Jude Medical's EnligHTN System, Boston Scientific's Vessix V2 Renal Denervation System, Covidien's OneShot System, Recor's Paradise System, Terumo's Iberis System and Cordis Corporation's RENLANE Renal Denervation System. Currently[ when? ], no renal denervation device has FDA approval.[ citation needed ]

Procedure

The procedure involves endovascular access via the femoral artery with advancement of a catheter-mounted device into the renal artery. The device uses radiofrequency or ultrasound to ablate the renal nerves. Typically, numerous ablations are applied at a different longitudinal and rotational positions to ensure maximal denervation. [13] The procedure does not involve a permanent implant.[ citation needed ]

Benefits

The most widely discussed studies to date are the Symplicity HTN-1, HTN-2 and HTN-3 trials, conducted with Medtronic's Symplicity RDN System.[ citation needed ]

Symplicity HTN-1 [3] looked at outcomes in 153 patients that underwent catheter-based renal denervation. Three-year follow-up data have demonstrated an average blood pressure reduction of -33/-19mm Hg.

Symplicity HTN-2 was a randomized, [2] controlled trial that compared 54 control patients with 52 patients who underwent catheter-based renal denervation. Six month follow-up data demonstrated a blood pressure reduction of -32/12 mm Hg in the treated group compared with a change of 1/0 mm Hg in the control group.

Meta-analyses of renal denervation have yielded conflicting results. [14] Whilst office systolic blood pressure reductions typically average around 30 mmHg, reductions observed on ambulatory blood pressure monitoring are typically much smaller, around 10 mmHg. [15] Explanations offered for this mismatch include renal denervation obliterating the white coat response, thereby disproportionately reducing clinic pressures, [14] or inadvertent bias arising from the unblinded design and lack of sham control procedure in almost all renal denervation trial designs to date. [15] [16]

A study published in 2014, Symplicity HTN-3, was a prospective, single-blind, randomised, sham-controlled trial in which 535 patients with severe resistant hypertension were randomized to undergo renal denervation or a sham procedure (in a 2:1 ratio). The results showed no statistically significant difference between renal denervation and the sham procedure. [4]

Following the publication of Symplicity HTN-3 the Joint UK Societies produced a consensus statement that did not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice. However they advocated further research with better designed randomised studies. [5]

More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure. [6] [7] [8] [17]

Risks

The Symplicity HTN-1, HTN-2 and HTN-3 trials have demonstrated acceptable safety profiles for catheter based renal denervation. Patients may experience pain during application of radiofrequency pulses and intraprocedural bradycardia requiring atropine has also been reported. [2] Other documented procedure related complications include femoral artery pseudoaneurysm and renal artery dissection.[ citation needed ]

Of particular concern is the theoretical risk of damage to renal arteries during delivery of radiofrequency energy. An animal study using swine showed no damage to the renal arteries at 6 month follow up. This finding is further supported in human studies in the HTN-1 and HTN-2 trial where follow up imaging has not demonstrated renal vascular damage. [18]

Other indications

Other diseases may be associated with an overactive sympathetic drive and therefore, in theory, renal denervation could be of benefit. Congestive heart failure (CHF), left ventricular hypertrophy (LVH), atrial fibrillation (AF), obstructive sleep apnea (OSA), and insulin resistance/type 2 diabetes mellitus (DM) all have been associated with increased activity of the sympathetic nervous system.[ citation needed ] Current clinical trials are examining the effect of renal denervation in these conditions. [19]

Related Research Articles

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<span class="mw-page-title-main">Cardiology</span> Branch of medicine dealing with the heart

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<span class="mw-page-title-main">Hypertension</span> Long-term high blood pressure in the arteries

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<span class="mw-page-title-main">Pulse pressure</span> Difference between systolic and diastolic blood pressure

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<span class="mw-page-title-main">Denervation</span> Loss of nerve supply

Denervation is any loss of nerve supply regardless of the cause. If the nerves lost to denervation are part of the neuronal communication to a specific function in the body then altered or a loss of physiological functioning can occur. Denervation can be caused by injury or be a symptom of a disorder like ALS, post-polio syndrome, or POTS. Additionally, it can be a useful surgical technique to alleviate major negative symptoms, such as in renal denervation. Denervation can have many harmful side effects such as increased risk of infection and tissue dysfunction.

The modern history of hypertension begins with the understanding of the cardiovascular system based on the work of physician William Harvey (1578–1657), who described the circulation of blood in his book De motu cordis. The English clergyman Stephen Hales made the first published measurement of blood pressure in 1733. Descriptions of what would come to be called hypertension came from, among others, Thomas Young in 1808 and especially Richard Bright in 1836. Bright noted a link between cardiac hypertrophy and kidney disease, and subsequently kidney disease was often termed Bright's disease in this period. In 1850 George Johnson suggested that the thickened blood vessels seen in the kidney in Bright's disease might be an adaptation to elevated blood pressure. William Senhouse Kirkes in 1855 and Ludwig Traube in 1856 also proposed, based on pathological observations, that elevated pressure could account for the association between left ventricular hypertrophy to kidney damage in Bright's disease. Samuel Wilks observed that left ventricular hypertrophy and diseased arteries were not necessarily associated with diseased kidneys, implying that high blood pressure might occur in people with healthy kidneys; however, the first report of elevated blood pressure in a person without evidence of kidney disease was made by Frederick Akbar Mahomed in 1874 using a sphygmograph. The concept of hypertensive disease as a generalized circulatory disease was taken up by Sir Clifford Allbutt, who termed the condition "hyperpiesia". However, hypertension as a medical entity really came into being in 1896 with the invention of the cuff-based sphygmomanometer by Scipione Riva-Rocci in 1896, which allowed blood pressure to be measured in the clinic. In 1905, Nikolai Korotkoff improved the technique by describing the Korotkoff sounds that are heard when the artery is ausculted with a stethoscope while the sphygmomanometer cuff is deflated. Tracking serial blood pressure measurements was further enhanced when Donal Nunn invented an accurate fully automated oscillometric sphygmomanometer device in 1981.

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Refractory Hypertension, also known as a refractory hypertensive state, RfHTN, or status angiotensus, is a hypertensive condition which can occur, for no apparent reason, in patients with previously well-managed hypertension. Refractory hypertension is characterized by a blood pressure that remains uncontrolled on maximal or near-maximal therapy, which is the use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and spironolactone. Patients with refractory hypertension typically exhibit increased sympathetic nervous system activity. The phenotype of refractory hypertension was first proposed in a retrospective analysis of patients referred to the University of Alabama at Birmingham Hypertension Clinic whose blood pressure could not be controlled on any antihypertensive regimen.

References

  1. ↑ Goel A (3 June 2016). "Renal sympathetic denervation". Radiopaedia . doi: 10.53347/rID-37149 . Retrieved 8 June 2022.
  2. 1 2 3 4 Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M (December 2010). "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial". Lancet. 376 (9756): 1903–9. doi:10.1016/S0140-6736(10)62039-9. PMID   21093036. S2CID   22838976. S2CID link provides full text access with a free registration; DOI link requires a subscription to get full text access.
  3. 1 2 Symplicity HTN-1 Investigators (May 2011). "Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months". Hypertension. 57 (5): 911–7. doi: 10.1161/HYPERTENSIONAHA.110.163014 . PMID   21403086.
  4. 1 2 Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, Leon MB, Liu M, Mauri L, Negoita M, Cohen SA, Oparil S, Rocha-Singh K, Townsend RR, Bakris GL, et al. (SYMPLICITY HTN-3 Investigators) (April 2014). "A controlled trial of renal denervation for resistant hypertension". The New England Journal of Medicine. 370 (15): 1393–401. doi: 10.1056/NEJMoa1402670 . PMID   24678939.
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  8. 1 2 Azizi (2018). "Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial". Lancet. 391 (10137): 2335–2345. doi:10.1016/S0140-6736(18)31082-1. PMID   29803590. S2CID   44132340.(subscription required)
  9. ↑ Doumas M, Douma S (April 2009). "Interventional management of resistant hypertension". Lancet. 373 (9671): 1228–30. doi:10.1016/S0140-6736(09)60624-3. PMID   19332354. S2CID   10869508.(subscription required)
  10. ↑ Doumas M, Faselis C, Papademetriou V (February 2010). "Renal sympathetic denervation and systemic hypertension". The American Journal of Cardiology. 105 (4): 570–6. doi:10.1016/j.amjcard.2009.10.027. PMID   20152255.(subscription required)
  11. ↑ Joffres M, Falaschetti E, Gillespie C, Robitaille C, Loustalot F, Poulter N, McAlister FA, Johansen H, Baclic O, Campbell N (August 2013). "Hypertension prevalence, awareness, treatment and control in national surveys from England, the USA and Canada, and correlation with stroke and ischaemic heart disease mortality: a cross-sectional study". BMJ Open. 3 (8): e003423. doi:10.1136/bmjopen-2013-003423. PMC   3758966 . PMID   23996822.
  12. ↑ Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM, et al. (American Heart Association Professional Education Committee) (June 2008). "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. 117 (25): e510–26. doi: 10.1161/CIRCULATIONAHA.108.189141 . PMID   18574054.
  13. 1 2 Mafeld S, Vasdev N, Haslam P (December 2012). "Renal denervation for treatment-resistant hypertension". Therapeutic Advances in Cardiovascular Disease. 6 (6): 245–58. doi:10.1177/1753944712468040. PMID   23132232. S2CID   38186874.
  14. 1 2 Doumas M, Anyfanti P, Bakris G (May 2012). "Should ambulatory blood pressure monitoring be mandatory for future studies in resistant hypertension: a perspective". Journal of Hypertension. 30 (5): 874–6. doi:10.1097/HJH.0b013e328352c3c7. PMID   22495128.(subscription required)
  15. 1 2 Howard JP, Nowbar AN, Francis DP (November 2013). "Size of blood pressure reduction from renal denervation: insights from meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design: the CONVERGE report" (PDF). Heart. 99 (21): 1579–87. doi:10.1136/heartjnl-2013-304238. PMID   24038167. S2CID   42540144. Archived from the original (PDF) on 13 February 2015. Internet Archive link provide free access to the manuscript; DOI link requires a subscription; S2CID link does not provide access to manuscript.
  16. ↑ Shun-Shin MJ, Howard JP, Francis DP (March 2014). "Removing the hype from hypertension". BMJ. 348: g1937. doi:10.1136/bmj.g1937. PMID   24603957. S2CID   206901791.
  17. ↑ Mahfoud F, Kandzari DE, Kario K, Townsend RR, Weber MA, Schmieder RE, et al. (9 April 2022). "Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial". The Lancet. 399 (10333): P1401-1410. doi:10.1016/S0140-6736(22)00455-X. PMID   35390320. S2CID   247943586.(subscription required)
  18. ↑ Rippy MK, Zarins D, Barman NC, Wu A, Duncan KL, Zarins CK (December 2011). "Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety" (PDF). Clinical Research in Cardiology. 100 (12): 1095–101. doi:10.1007/s00392-011-0346-8. PMID   21796327. S2CID   6084237. Archived from the original (PDF) on 8 September 2015. Internet Archive provides access to free full text; DOI link requires subscription; S2CID link does not provide access to the manuscript.
  19. ↑ "RDN Beyond Hypertension". RDN World. Archived from the original on 29 November 2013.
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