Description of Procedure or Service

Uncontrolled Hypertension

Hypertension is estimated to affect approximately 30% of the population in the U.S. It accounts for a high burden of morbidity related to stroke, ischemic heart disease, kidney disease, and peripheral arterial disease. An estimated 1 in 4 adults with hypertension have their hypertension under control, but the remaining 77% (93 million) remain uncontrolled. Uncontrolled hypertension is diagnosed when an individual's blood pressure remains above targeted levels when a patient either is not using, or unable to use, treatments to control blood pressure or when hypertension persists despite antihypertensive therapies. The definition of uncontrolled hypertension is inclusive of resistant hypertension in which blood pressure remains above the targeted range despite the use of 3 or more antihypertensive medications, including a diuretic, with complementary mechanisms of action. A number of factors may contribute to uncontrolled hypertension, including non-adherence to medications, excessive salt intake, inadequate doses of medications, excess alcohol intake, volume overload, drug-induced hypertension, and other forms of secondary hypertension. Also, it is sometimes necessary to address comorbid conditions (ie, obstructive sleep apnea) to control blood pressure adequately.

Radiofrequency Denervation of the Renal Sympathetic Nerves

Increased sympathetic nervous system activity has been linked to essential hypertension. Surgical sympathectomy has been shown to be effective in reducing blood pressure but is limited by the adverse side effects of surgery and was largely abandoned after effective medications for hypertension became available. The renal sympathetic nerves arise from the thoracic nerve roots and innervate the renal artery, the renal pelvis, and the renal parenchyma. Radiofrequency ablation (RFA) of the renal sympathetic nerves is thought to decrease both the afferent sympathetic signals from the kidney to the brain and the efferent signals from the brain to the kidney. The procedure decreases sympathetic activation, decreases vasoconstriction, and decreases activation of the renin-angiotensin system.

The procedure is performed percutaneously with access at the femoral artery. A flexible catheter is threaded into the renal artery and controlled low-power RF energy, is delivered to the arterial walls where the renal sympathetic nerves are located. Once adequate RF energy has been delivered to ablate the sympathetic nerves, the catheter is removed.

Ultrasound Denervation of the Renal Sympathetic Nerves

Ultrasound renal denervation (usRDN) is a minimally invasive procedure designed to treat hypertension by disrupting renal sympathetic nerves. The procedure targets the same physiological mechanism as radiofrequency ablation, aiming to decrease both afferent and efferent sympathetic signaling between the kidneys and the brain. This reduction in sympathetic activation is thought to decrease vasoconstriction and inhibit the renin-angiotensin system, ultimately leading to blood pressure reduction. The usRDN procedure is typically performed under local anesthesia with conscious sedation. Access is obtained through the femoral artery, and the catheter is advanced to the renal artery under fluoroscopic guidance. Once positioned, the catheter's balloon is inflated with cooling fluid, and ultrasound energy is delivered. Usually, 2-3 ultrasound emissions are delivered per renal artery, with the ability to treat both main renal arteries and accessory renal arteries when present.

Regulatory Status

The Symplicity Spyral™ Renal Denervation System (Medtronic, Inc) is a multielectrode RFA catheter system designed to deliver 4-quadrant ablations and was approved by the U.S. Food and Drug Administration (FDA) in November 2023. The Paradise® Ultrasound Renal Denervation System (ReCor Medical, Inc) also received FDA approval in November 2023. Both systems are indicated to reduce blood pressure as an adjunctive treatment in individuals with hypertenison for whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure.

No other renal denervation devices are currently FDA approved for the treatment of hypertension. Several other devices that were previously in development, such as the EnligHTN™ system (St. Jude Medical) and Vessix™ system (Boston Scientific), are no longer being marketed for this indication.

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

Radiofrequency ablation and ultrasound ablation of the renal sympathetic nerves are considered investigational.  BCBSNC does not provide coverage for investigational services or procedures.

Benefits Application

This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy.

When Renal Denervation is covered

Not applicable.

When Renal Denervation is not covered

Radiofrequency ablation and ultrasound ablation of the renal sympathetic nerves are considered investigational for the treatment of uncontrolled hypertension.

Policy Guidelines

For individuals who have uncontrolled hypertension, despite the use of anti-hypertensive medications, who receive RFA of the renal sympathetic nerves, the evidence includes several RCTs, numerous systematic reviews of the RCTs, and a multinational registry study. Relevant outcomes are symptoms, change in disease status, morbid events, medication use, and treatment-related morbidity. The proof of principle SPYRAL HTN-OFF MED study found that multielectrode renal denervation was superior to sham in the absence of background antihypertensive medication therapy, with between-group differences of -4.0 mmHg for 24-h SBP and -6.6 for office SBP at 3 months. The unpowered SPYRAL HTN-ON MED Pilot study also found significant between-group differences of -7.4 mmHg for 24-h SBP and -6.8 mmHg for office SBP at 6 months; however, results were only significant for the subgroup of patients non-adherent to medications. Long-term data from the SPYRAL HTN-ON MED study suggest that blood pressure reductions with multielectrode renal denervation are progressive and sustained over time. The SPYRAL HTN-ON MED Expansion study failed to meet its primary efficacy endpoint and found only 0.03 mmHg difference between renal denervation and sham control groups at 6 months follow-up. A significant reduction in office blood pressure was noted at 6 months (-4.1 mmHg). Confounding of these outcome estimates by unbalanced medication changes, missing 24-h SBP outcome data, and timing of antihypertensive medications related to 24-h SBP assessment may explain the discordant results between the pilot and expansion phases of this trial. Study interpretation is also complicated by short-term blinded follow-up and imputation of excluded crossover patient data. It is unclear which patients are most likely to derive benefit, and currently, there is no practical method to verify nerve destruction following ablation. Evidence from systematic reviews and meta-analyses are conflicting, but all available studies included evidence from both first and second-generation Symplicity catheters as well as multiple renal denervation methodologies such as ultrasound. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have uncontrolled hypertension, despite the use of anti-hypertensive medications, who receive ultrasound renal denervation (usRDN), the evidence includes 4 randomized sham-controlled trials, 1 RCT comparing usRDN to radiofrequency-based renal denervation, and a pooled analysis of 3 sham-controlled RCTs. Relevant outcomes are changes in blood pressure, medication use, and treatment-related morbidity. Two trials, RADIANCE-HTN SOLO and RADIANCE II evaluated usRDN in patients with no antihypertensive medication usage for 2 months post-intervention. The RADIANCE-HTN SOLO trial demonstrated that usRDN was superior to sham, with a between-group difference of -6.3 mmHg for daytime ambulatory systolic blood pressure (SBP) at 2 months. The RADIANCE II trial showed similar results, also showing a -6.3 mmHg difference in daytime ambulatory SBP at 2 months. The RADIANCE-HTN TRIO trial, focusing on resistant hypertension inpatients with a standardized triple combination antihypertensive treatment, found a -4.5 mmHg difference in daytime ambulatory SBP at 2 months. The REQUIRE trial, conducted in Asian populations, did not show a significant difference between usRDN and sham control, possibly due to study design limitations. Long-term data from these trials show mixed results: while studies suggest that BP reductions with usRDN are sustained over time, the differences between usRDN and sham control groups diminished at 6 or 12 months after medication titration in some trials. However, the FDA's summary of safety and effectiveness data for the RADIANCE-HTN TRIO and SOLO trials demonstrated superior office systolic blood pressure reductions with usRDN compared to sham control at 24 and 36 months. Notably, these improved outcomes in the usRDN group were achieved despite patients using fewer antihypertensive medications than the sham control group. A meta-analysis of the sham-controlled RADIANCE trials showed that fewer usRDN patients required additional antihypertensive medications and demonstrated significant reductions in ambulatory, home, and office SBP at 6 months. Adverse events were infrequent and similar between usRDN and sham groups across studies. The RADIOSOUND-HTN trial compared 3 renal denervation techniques in patients with resistant hypertension who were on a stable regimen of antihypertensive medications. The trial found that usRDN showed superiority over radiofrequency ablation (RFA) of main renal arteries in reducing daytime ambulatory SBP at 3 months, while RFA of main arteries plus branches did not significantly differ from the other groups. While these results are promising, there was high variability in patient responses suggesting that further research may be needed to identify who is most likely to benefit from usRDN. Additionally, there is currently no practical method to verify nerve destruction following ablation.The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 0338T, 0339T, 0935T, C1735, C1736

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Scientific Background and Reference Sources

For policy titled: Radiofrequency Ablation of the Renal Nerves as a Treatment of Hypertension

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 8/9/12

National Institutes of Health (NIH). Clinical trial #NCT01418261. Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3). Retrieved from http://clinicaltrials.gov/ct2/show/NCT01418261?term=NCT01418261&rank=1

Doumas M, Papademetriou V, Douma S et al. Benefits from treatment and control of patients with resistant hypertension. Int J Hypertens 2010; 2011:318549. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014695/

Thomas G, Shishehbor MH, Bravo EL, Nally JV. Renal denervation to treat resistant hypertension: Guarded optimism. Cleve Clin J Med. 2012 Jul;79(7):501-10. Retrieved from http://www.ccjm.org/content/79/7/501.long

Schlaich MP, Hering D, Sobotka P, Krum H, et al., Effects of renal denervation on sympathetic activation, blood pressure, and glucose metabolism in patients with resistant hypertension. Front Physiol. 2012;3:10. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270497/

Bunte MC, Infante de Oliveira E, Shishehbor MH. Endovascular Treatment of Resistant and Uncontrolled Hypertension, Therapies on the Horizon. J Am Coll Cardiol Intv. 2013;6(1):1-9. Retrieved from http://interventions.onlinejacc.org/article.aspx?articleid=1487128#topLocation

National Institutes of Health (NIH). Clinical trial #NCT01541865. Treatment of Resistant Hypertension Using a Radiofrequency Percutaneous Transluminal Angioplasty Catheter (REDUCE-HTN). Retrieved from http://clinicaltrials.gov/ct2/show/NCT01541865?term=REDUCE-HTN&rank=1

National Institutes of Health (NIH). Clinical trial #NCT01438229. Safety and Efficacy Study of Renal Artery Ablation in Resistant Hypertension Patients (EnligHTN I). Retrieved from http://clinicaltrials.gov/ct2/show/NCT01438229

Medical Director review 3/2013

Specialty Matched Consultant Advisory Panel review 4/2013

Lambert GW, Hering D, Esler MD et al. Health-related quality of life after renal denervation in patients with treatment-resistant hypertension. Hypertension 2012; 60(6):1479-84.

Ott C, Mahfoud F, Schmid A et al. Renal denervation in moderate treatment resistant hypertension.
J Am Coll Cardiol 2013.

Schlaich MP1, Schmieder RE, Bakris G. International expert consensus statement: Percutaneous transluminal renal denervation for the treatment of resistant hypertension. J Am Coll Cardiol. 2013 Dec 3;62(22):2031-45.

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 9/12/13

Medical Director review 4/2014

Specialty Matched Consultant Advisory Panel review 4/2014

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 9/11/14

Specialty Matched Consultant Advisory Panel review 4/2015

Medical Director review 4/2015

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 9/10/15

Specialty Matched Consultant Advisory Panel review 4/2016

Medical Director review 4/2016

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 9/2016

Specialty Matched Consultant Advisory Panel review 4/2017

Medical Director review 4/2017

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 9/2017

Specialty Matched Consultant Advisory Panel review 4/2018

Medical Director review 4/2018

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 9/2018

Medical Director review 9/2018

Specialty Matched Consultant Advisory Panel review 4/2019

Medical Director review 4/2019

Specialty Matched Consultant Advisory Panel review 4/2020

Medical Director review 4/2020

BCBSA Medical Policy Reference Manual [Electronic Version]. 7.01.136, 10/2020

Specialty Matched Consultant Advisory Panel review 4/2021

Medical Director review 4/2021

Specialty Matched Consultant Advisory Panel review 4/2022

Medical Director review 4/2022

Townsend RR, Mahfoud F, Kandzari DE, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. Nov 11 2017; 390(10108): 2160-2170. PMID 28859944

Bohm M, Kario K, Kandzari DE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. May 02 2020; 395(10234): 1444-1451. PMID 32234534

Kandzari DE, Bohm M, Mahfoud F, et al. 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. Lancet. Jun 09 2018; 391(10137): 2346-2355. PMID 29803589

Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. Apr 09 2022; 399(10333): 1401-1410. PMID 35390320

Kandzari DE, Kario K, Mahfoud F, et al. The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. Am Heart J. Jan 2016; 171(1): 82-91. PMID 26699604

Specialty Matched Consultant Advisory Panel review 4/2023

Medical Director review 4/2023

Acelajado MC, Calhoun DA. Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment. Cardiol Clin. Nov 2010; 28(4): 639-54. PMID 20937447

Centers for Disease Control and Prevention (CDC). Facts About Hypertension, Updated July 6, 2023; https://www.cdc.gov/bloodpressure/facts.htm.

Food and Drug Administration (FDA) Circulatory System Devices Panel. FDA Executive Summary, Premarket Application (PMA) for Pxxxxxx Medtronic, Inc. Symplicity Spyral Renal Denervation System. 2023; https://www.fda.gov/media/171411/download

Zile MR, Little WC. Effects of autonomic modulation: more than just blood pressure. J Am Coll Cardiol. Mar 06 2012; 59(10): 910-2. PMID 22381426

Specialty Matched Consultant Advisory Panel review 4/2024

Medical Director review 4/2024

For policy titled: Renal Denervation as a Treatment of Hypertension

Cluett JL, Blazek O, Brown AL, et al. Renal Denervation for the Treatment of Hypertension: A Scientific Statement From the American Heart Association. Hypertension. Oct 2024; 81(10): e135-e148. PMID 39101202

National Institute for Health and Care Excellence (NICE). Interventional procedures guidance: Percutaneous transluminal radiofrequency sympathetic denervation of the renal artery for resistant hypertension [IPG418]. March 2023; https://www.nice.org.uk/guidance/ipg754. 

Azizi M, Sharp ASP, Fisher NDL, et al. Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program. Circulation. Mar 05 2024; 149(10): 747-759. PMID 37883784

Fengler K, Rommel KP, Blazek S, et al. A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN). Circulation. Jan 29 2019; 139(5): 590-600. PMID 30586691

Azizi M, Sanghvi K, Saxena M, et al. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet. Jun 26 2021; 397(10293): 2476-2486. PMID 34010611

Kario K, Bhatt DL, Brar S, et al. Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure: Insights From SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. Hypertension. Dec 2015; 66(6): 1130-7. PMID 26558819

Azizi M, Schmieder RE, Mahfoud F, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. Jun 09 2018; 391(10137): 2335-2345. PMID 29803590

Azizi M, Saxena M, Wang Y, et al. Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial. JAMA. Feb 28 2023; 329(8): 651-661. PMID 36853250

Azizi M, Schmieder RE, Mahfoud F, et al. Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial. Circulation. May 28 2019; 139(22): 2542-2553. PMID 30880441

Azizi M, Daemen J, Lobo MD, et al. 12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation. JACC Cardiovasc Interv. Dec 28 2020; 13(24): 2922-2933. PMID 33357531

Rader F, Kirtane AJ, Wang Y, et al. Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the treatment arm of the randomised RADIANCE-HTN SOLO trial. EuroIntervention. Oct 07 2022; 18(8): e677-e685. PMID 35913759

Azizi M, Mahfoud F, Weber MA, et al. Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation: Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial. JAMA Cardiol. Dec 01 2022; 7(12): 1244-1252. PMID 36350593

Kario K, Yokoi Y, Okamura K, et al. Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial. Hypertens Res. Feb 2022; 45(2): 221-231. PMID 34654905

Food and Drug Administration (FDA). Summary of Safety and Effectiveness Data (SSED) - Paradise Ultrasound Renal Denervation System - P220023B. 2023; https://www.accessdata.fda.gov/cdrh_docs/pdf22/P220023B.pdf.

Specialty Matched Consultant Advisory Panel review 4/2025

Medical Director review 4/2025

Policy Implementation/Update Information

For policy titled: Radiofrequency Ablation of the Renal Nerves as a Treatment of Hypertension

10/30/12 New policy developed. Radiofrequency ablation of the renal sympathetic nerves is considered investigational for treatment of resistant hypertension. Medical Director review 10/2012. (mco)

5/14/13 Specialty Matched Consultant Advisory Panel review 4/2013. Medical Director review 3/2013. New product information added to Description section. References updated. (mco)

12/31/13 Deleted unlisted code 64999 and added CPT codes 0338T and 0339T to Billing/Coding section. (mco)

5/13/14 Description section updated. References updated. Specialty Matched Consultant Advisory Panel review 4/2014. Medical Director review 4/2014. No changes to Policy Statements. (mco)

11/11/14 References updated. No changes to Policy Statements. (td)

5/26/15 Specialty Matched Consultant Advisory Panel review 4/2015. Medical Director review 4/2015. Policy Statements remain unchanged. (td)

10/30/15 Description section: Regulatory Status updated. Policy Guidelines section extensively revised. References updated. (td)

5/31/16 Specialty Matched Consultant Advisory Panel review 4/27/2016. Medical Director review 4/2016. (jd)

5/26/17 References updated. Specialty Matched Consultant Advisory Panel review 4/2017. Medical Director review 4/2017. (jd)

5/11/18 References updated. Specialty Matched Consultant Advisory Panel 4/2018. Medical Director review 4/2018. (jd)

10/12/18 Minor revisions to regulatory status and policy guidelines. No change to policy intent. Reference updated. Medical Director review. 9/2018. (jd)

5/14/19 Specialty Matched Consultant Advisory Panel review 4/2019. Medical Director review 4/2019. (jd)

12/10/19 The following code was removed from the Billing/Coding section effective 10/1/19: 0339T. (jd)

4/28/20 Specialty Matched Consultant Advisory Panel review 4/2020. Medical Director review 4/2020. (jd)

5/4/21 Minor revisions to regulatory status and policy guidelines. References updated. Specialty Matched Consultant Advisory Panel review 4/2021. Medical Director review 4/2021. (jd)

5/3/22 References updated. Specialty Matched Advisory Panel review 4/2022. Medical Director review 4/2021. (jd)

5/16/23 Description, Policy Guidelines and References updated. Specialty Matched Advisory Panel review 4/2023. Medical Director review 4/2023. (tm)

5/1/24 Description, Policy Guidelines and References updated. Not Covered section edited for clarity, replaced “resistant” hypertension with “uncontrolled” hypertension. No change to policy statement. Specialty Matched Advisory Panel review 4/2024. Medical Director review 4/2024. (tm)

12/31/24 Code 0339T added to Billing/Coding section. New codes 0935T, C1735, C1736 added to Billing/Coding section, effective 1/1/2025. (tm)

For policy titled: Renal Denervation as a Treatment of Hypertension

5/14/25 Title changed to Renal Denervation as a Treatment of Hypertension. Policy statement updated and now reads: “Radiofrequency ablation and ultrasound ablation of the renal sympathetic nerves are considered investigational.  BCBSNC does not provide coverage for investigational services or procedures.” Description and Policy Guidelines sections updated to include information regarding ultrasound renal denervation. Regulatory and References sections updated. Not Covered section updated and now reads “Radiofrequency ablation and ultrasound ablation of the renal sympathetic nerves are considered investigational for the treatment of uncontrolled hypertension.” Specialty Matched Advisory Panel review 4/2025. Medical Director review 4/2025. Notification given 5/14/25 for effective date 7/16/25. (tm)