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]

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.

In August 2023, the US FDA panel recommended the device from ReCor while rejecting the device from Medtronic.[14][15]

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.[16] 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.[17] Explanations offered for this mismatch include renal denervation obliterating the white coat response, thereby disproportionately reducing clinic pressures,[16] or inadvertent bias arising from the unblinded design and lack of sham control procedure in almost all renal denervation trial designs to date.[17][18]

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][19]

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.[20]

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.[21]

References

  1. ^ Goel A (3 June 2016). "Renal sympathetic denervation". Radiopaedia. doi:10.53347/rID-37149. Retrieved 8 June 2022.
  2. ^ a b c d 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. ^ a b 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.((cite journal)): CS1 maint: numeric names: authors list (link)
  4. ^ a b 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.
  5. ^ a b c Lobo MD, de Belder MA, Cleveland T, Collier D, Dasgupta I, Deanfield J, Kapil V, Knight C, Matson M, Moss J, Paton JF, Poulter N, Simpson I, Williams B, Caulfield MJ, et al. (British Cardiovascular Intervention Society) (January 2015). "Joint UK societies' 2014 consensus statement on renal denervation for resistant hypertension". Heart. 101 (1): 10–6. doi:10.1136/heartjnl-2014-307029. PMC 4283620. PMID 25431461.
  6. ^ a b Bohm (2020). "Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial". Lancet. 395 (10234): 1444–1451. doi:10.1016/S0140-6736(20)30554-7. PMID 32234534. S2CID 214699992.(subscription required)
  7. ^ a b Kandzari (2018). "Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial" (PDF). Lancet. 391 (10137): 2346–2355. doi:10.1016/S0140-6736(18)30951-6. PMID 29803589. S2CID 44126211. S2CID link provides free access (with registration) to an apparent draft of the manuscript. DOI full text access requires a subscription.
  8. ^ a b 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. ^ a b 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. ^ "US FDA panel votes against use of Medtronic's blood pressure treatment device". Reuters. 2023-08-24. Retrieved 2023-08-24.
  15. ^ Roy, Sriparna (2023-08-22). "US FDA panel backs Otsuka's blood pressure treatment device". Reuters. Retrieved 2023-08-24.
  16. ^ a b 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)
  17. ^ a b 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.
  18. ^ 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.
  19. ^ 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)
  20. ^ 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.
  21. ^ "RDN Beyond Hypertension". RDN World. Archived from the original on 29 November 2013.
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