Renal sympathetic denervation

Jump to navigation Jump to search

WikiDoc Resources for Renal sympathetic denervation

Articles

Most recent articles on Renal sympathetic denervation

Most cited articles on Renal sympathetic denervation

Review articles on Renal sympathetic denervation

Articles on Renal sympathetic denervation in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Renal sympathetic denervation

Images of Renal sympathetic denervation

Photos of Renal sympathetic denervation

Podcasts & MP3s on Renal sympathetic denervation

Videos on Renal sympathetic denervation

Evidence Based Medicine

Cochrane Collaboration on Renal sympathetic denervation

Bandolier on Renal sympathetic denervation

TRIP on Renal sympathetic denervation

Clinical Trials

Ongoing Trials on Renal sympathetic denervation at Clinical Trials.gov

Trial results on Renal sympathetic denervation

Clinical Trials on Renal sympathetic denervation at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Renal sympathetic denervation

NICE Guidance on Renal sympathetic denervation

NHS PRODIGY Guidance

FDA on Renal sympathetic denervation

CDC on Renal sympathetic denervation

Books

Books on Renal sympathetic denervation

News

Renal sympathetic denervation in the news

Be alerted to news on Renal sympathetic denervation

News trends on Renal sympathetic denervation

Commentary

Blogs on Renal sympathetic denervation

Definitions

Definitions of Renal sympathetic denervation

Patient Resources / Community

Patient resources on Renal sympathetic denervation

Discussion groups on Renal sympathetic denervation

Patient Handouts on Renal sympathetic denervation

Directions to Hospitals Treating Renal sympathetic denervation

Risk calculators and risk factors for Renal sympathetic denervation

Healthcare Provider Resources

Symptoms of Renal sympathetic denervation

Causes & Risk Factors for Renal sympathetic denervation

Diagnostic studies for Renal sympathetic denervation

Treatment of Renal sympathetic denervation

Continuing Medical Education (CME)

CME Programs on Renal sympathetic denervation

International

Renal sympathetic denervation en Espanol

Renal sympathetic denervation en Francais

Business

Renal sympathetic denervation in the Marketplace

Patents on Renal sympathetic denervation

Experimental / Informatics

List of terms related to Renal sympathetic denervation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Synonyms and keywords: RDN; Renal denervation

Overview

Renal denervation (RDN) is a minimally invasive, endovascular catheter-based procedure. It most commonly uses a radiofrequency energy source and aims to treat hypertension in selected patients whose blood pressure can't be controlled with a combination of lifestyle changes and antihypertensive therapy. A patient is said to have resistant hypertension when despite these changes and taking 3 or more antihypertensive drugs, including a diuretic drug, at their maximal tolerated doses, without secondary hypertension, has a baseline systolic blood pressure of more that 160 mm Hg (or more that 150 mm Hg, in case of concomitant type 2 diabetes mellitus). [1] This treatment is based on the fact that these patients have an increase in sympathetic outflow. [2] By applying radiofrequency energy pulses to the renal arteries, the nerves in the vascular wall (adventitia layer) can be ablated. This causes a reduction of renal sympathetic afferent and efferent activity with the intent to decrease blood pressure. [3] This specific interruption of the renal sympathetic nerves appears to offer a durable blood pressure decrease, without severe consequences. [1] Early data from international clinical trials shows promising results, demonstrating an average blood pressure reduction of approximately 30mm Hg at three year follow up in patients with treatment-resistant hypertension. [4][5] Since 2007, over 4000 patients have undergone catheter-based renal denervation with the Medtronic Symplicity™ Renal Denervation System. [6] Despite its importance in drug-resistant hypertensive patients, by reducing renal sympathetic nerve flow, this procedure will also reduce overall sympathetic activity, thereby affecting multiple organs, which is why renal denervation might also be beneficial in other disease states, such as congestive heart failure, chronic kidney disease, metabolic syndrome and others. [7] Until now, few complications have been reported, being inconsequential. It's long-term efficacy is still yet to be determined, however, studies show a permanence of effect at least of 2 to 3 years. [2][8]

History

Prior to pharmacological management of hypertension, surgical sympathectomy was a recognized treatment for hypertension. Before modern pharmacotherapy, the mortality rate within 5 years of malignant hypertension was close to 100%. [1] Surgical treatment of hypertension was suggested by several independent researchers in 1923, yet the first patient with malignant hypertension was only treated with surgical sympathectomy, by Adson in 1925. [2] [9] Isolated bilateral kidney denervation was only performed in 1934 by Page and Heuer, however, because the results were considered unsatisfactory, surgical renal denervation was replaced by a more aggressive technique, the surgical removal of splanchnic nerves or splanchnicectomy, which showed effective results. Subsequently, thoracolumbar splanchnicectomy became the procedure of choice for malignant hypertension, which did not respond to diet and the limited pharmacological therapy of the time, for the following 2 decades. [2] Between 1938 and 1947, other studies were made by Smithwick and Thompson, who published results from studying 3500 patients with malignant hypertension. Of those, 2400 were treated with thoracolumbar splanchnicectomy, while the others took the pharmacological therapy available at the time. The group who underwent the surgical procedure had an inferior mortality rate and substantial blood pressure reduction, when compared to the pharmacologically treated group. [2] This technique was often successful in reducing blood pressure but due to its non-selective nature, the high operative mortality and side effects were considerable. [1] These included orthostatic hypotension, palpitations, anhidrosis, intestinal disturbances, impotence, thoracic duct injuries and atelactasis.[10][11] It was only until mid-1950's that the first oral antihypertensive medication became available. This allowed for a well-tolerated treatment regimen that patients could follow on the long term. For the last 50 years, this medication has improved the control of hypertension in thousands of patients throughout the world, however, an estimated 30% of hypertension cases are resistant and therefore not well managed with oral antihypertensive medications alone. [12][2] With this, the number of hypertensive patients being referred for splanchnicectomy has decreased considerably in recent years. During this time, a great effort in understanding the role of the SNS in hypertension has been made, particularly the role of renal sympathetic nerves in this process. [2] Several models are pointing to a considerable role of the SNS overactivity in the development and maintenance of hypertension, to which renal sympathetic nerves are an important contributor. This overactivity is involved in several others diseases, described below, which justifies more studies to evaluate the importance of this procedure in the treatment of other conditions. [2]

Device

Several devices have been approved for this procedure. One of them is the Symplicity™ Renal Denervation System, produced by Medtronic (formerly Ardian)[13] and consists of an endovascular catheter (6F), radiofrequency generator, dispersive electrodes, foot switch and power cable.[14] In Europe, the Symplicity device received CE mark approval in 2010.[15] The device is available in parts of Europe, Asia, Africa, Australia and the Americas.[6] The Symplicity device currently has over 5 years of clinical experience and 3 years of follow up data. The device has received favourable reviews on WhichMedicalDevice, but concerns have been reported regarding availability and financial reimbursement for the procedure.[16] There are a number of other devices that are currently being evaluated, but these different technologies have limited clinical data and do not have long term data. In addition to Medtronic's Symplicity system, five other renal denervation devices have a CE mark. These include St. Jude Medical’s EnligHTN™ System, Vessix's V2™ Renal Denervation System, Covidien’s OneShot™ System, Recor’s Paradise™ System and Terumo's Iberis™ System. Currently, no renal denervation device has FDA approval today.

Procedure

The Symplicity renal denervation system consists of a generator and a flexible catheter. During this minimally invasive procedure, the interventionalist uses a steerable catheter with a radio frequency (RF) energy electrode tip. The RF energy is delivered to a renal artery via standard femoral artery access. A series of 2-minute ablations are delivered along each renal artery to disrupt the nerves. The procedure does not involve a permanent implant.

Outcomes

The two biggest studies to date have been the Symplicity HTN-1 and HTN-2 trials, conducted with Medtronic's Symplicity RDN System.

Symplicity HTN-1 [4] 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 [5] was a randomized, 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 -32/12mm Hg in the treated group compared with a change of 1/0 mm Hg in the control group. Longer follow-up, more patients, and improved study design are necessary to further validate catheter-based renal denervation. Currently the Symplicity HTN-3 trial is underway in the US. This is a 530-patient, multi-centre, prospective, single-blind, randomized, controlled study (Clinical Trial No. NCT01418261).[17]

Meta-analyses of renal denervation have yielded conflicting results.[18] 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.[19] The reasons for this disparity are so far unclear. Proposed theories include renal denervation obliterating the white coat response, thereby disproportionately reducing clinic pressures,[18] or the disparity rather being an anomaly due to deficiencies in renal denervation trial designs to date.[19]

Risks

The Symplicity HTN-1 and HTN-2 trials have demonstrated a good safety profile for catheter based renal denervation. Patients may experience pain during application of radiofrequency pulses and intraprocedural bradycardia requiring atropine has also been reported.[5] Other documented procedure related complications include femoral artery pseudoaneurysm and renal artery dissection.

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]

Uses of Renal Denervation beyond Hypertension

Hypertension is associated with an overactive sympathetic drive and renal denervation is the ablation of the renal nerves stopping the cross-talk between the kidneys and brains, thus reducing the sympathetic drive. Similar to hypertension, 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 an overactive sympathetic drive. Current clinical trials are researching the effect of renal denervation in these clinical conditions as well. [21]

References

  1. 1.0 1.1 1.2 1.3 Thukkani, A. K.; Bhatt, D. L. (2013). "Renal Denervation Therapy for Hypertension". Circulation. 128 (20): 2251–2254. doi:10.1161/CIRCULATIONAHA.113.004660. ISSN 0009-7322.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Papademetriou, V.; Rashidi, A. A.; Tsioufis, C.; Doumas, M. (2014). "Renal Nerve Ablation for Resistant Hypertension: How Did We Get Here, Present Status, and Future Directions". Circulation. 129 (13): 1440–1451. doi:10.1161/CIRCULATIONAHA.113.005405. ISSN 0009-7322.
  3. Esler, MC (2010 Dec 4). "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomized controlled trial". Lancet. 376 (9756): 1903–9. doi:10.1016/S0140-6736(10)62039-9. PMID 21093036. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  4. 4.0 4.1 Symplicity HTN-1, Investigators (2011 May). "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. Check date values in: |date= (help)
  5. 5.0 5.1 5.2 Symplicity HTN-2, Investigators (2010 Dec 4). "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. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  6. 6.0 6.1 Medtronic. MEDTRONIC SYMPLICITY™ RENAL DENERVATION SYSTEM DEMONSTRATES SIGNIFICANT AND SUSTAINED BLOOD PRESSURE REDUCTION OUT TO THREE YEARS. [Press Release]. Retrieved from: http://www.medtronicrdn.com/pdfs/RDN_ACC_Press_Release_FINAL_03_25_12.pdf. April 4, 2012.
  7. Böhm M, Linz D, Urban D, Mahfoud F, Ukena C (2013). "Renal sympathetic denervation: applications in hypertension and beyond". Nat Rev Cardiol. 10 (8): 465–76. doi:10.1038/nrcardio.2013.89. PMID 23774592.
  8. Schlaich MP, Schmieder RE, Bakris G, Blankestijn PJ, Böhm M, Campese VM; et al. (2013). "International expert consensus statement: Percutaneous transluminal renal denervation for the treatment of resistant hypertension". J Am Coll Cardiol. 62 (22): 2031–45. doi:10.1016/j.jacc.2013.08.1616. PMID 24021387.
  9. Doumas, M (2009 Apr 11). "Interventional management of resistant hypertension". Lancet. 373 (9671): 1228–30. doi:10.1016/S0140-6736(09)60624-3. PMID 19332354. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  10. Doumas, M (2010 Feb 15). "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. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  11. Mahfoud, F.; Luscher, T. F.; Andersson, B.; Baumgartner, I.; Cifkova, R.; DiMario, C.; Doevendans, P.; Fagard, R.; Fajadet, J.; Komajda, M.; LeFevre, T.; Lotan, C.; Sievert, H.; Volpe, M.; Widimsky, P.; Wijns, W.; Williams, B.; Windecker, S.; Witkowski, A.; Zeller, T.; Bohm, M. (2013). "Expert consensus document from the European Society of Cardiology on catheter-based renal denervation". European Heart Journal. 34 (28): 2149–2157. doi:10.1093/eurheartj/eht154. ISSN 0195-668X.
  12. Calhoun, DA (2008 Jun 24). "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. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  13. WhichMedicalDevice. Symplicity Catheter System (Overview). http://www.whichmedicaldevice.com/by-manufacturer/113/198/symplicity-catheter-system [Accessed online April 5, 2012]
  14. Medtronic. RDN Brochure. http://www.medtronicrdn.com/mediakit/RDN%20Brochure.pdf [accessed online 7 April 2012].
  15. Medgadget. Medtronic Starts Trial with Symplicity Renal Denervation System for Chronic Heart Failure and Renal Impairment. [Published online 12 Feb 2012] [Accessed online 5 Apr 2012] http://medgadget.com/2012/02/medtronic-starts-trial-with-symplicity-renal-denervation-system-for-chronic-heart-failure-and-renal-impairment.html
  16. WhichMedicalDevice. Symplicity Catheter System (User Reviews). http://www.whichmedicaldevice.com/by-manufacturer/113/198/symplicity-catheter-system [Accessed online April 5, 2012]
  17. Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3). ClinicalTrials.gov Identifier: NCT01418261 http://clinicaltrials.gov/ct2/show/NCT01418261. [Accessed online 7 Apr 2012].
  18. 18.0 18.1 http://www.ncbi.nlm.nih.gov/pubmed/22495128
  19. 19.0 19.1 http://heart.bmj.com/content/early/2013/09/12/heartjnl-2013-304238.abstract
  20. Rippy, MK (2011 Dec). "Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety". Clinical research in cardiology : official journal of the German Cardiac Society. 100 (12): 1095–101. doi:10.1007/s00392-011-0346-8. PMID 21796327. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  21. www.renaldenervationworld.org