Medical Policy

 

Subject: Radiofrequency Ablation of the Renal Sympathetic Nerves
Document #: SURG.00135 Publish Date:    10/17/2018
Status: Reviewed Last Review Date:    09/13/2018

Description/Scope

This document addresses use of radiofrequency ablation (RFA) of the renal sympathetic nerves for all indications, including but not limited to, treatment for resistant hypertension.  

For information related to other techniques for the treatment of resistant hypertension, please see:

Position Statement

Investigational and Not Medically Necessary:

Radiofrequency ablation of the renal sympathetic nerves is considered investigational and not medically necessary for all indications.

Rationale

Radiofrequency ablation (RFA) is a minimally invasive surgical procedure utilizing low power radiofrequency energy to ablate (or destroy) various tissues of the body.  There are many RFA procedures that utilize specially designed ablation devices to treat multiple organ systems and disorders, such as cardiac arrhythmias, Barrett’s esophagus, malignant tumors, varicose veins and for pain management.  This document only addresses RFA procedures and devices specifically designed to ablate (or denervate) the sympathetic renal nerves for any indication, including but not limited to, the treatment of resistant hypertension (HTN). 

Resistant HTN is defined as blood pressure (BP) above goal despite treatment with three antihypertensive agents of different classes, ideally including a diuretic, all prescribed at optimal dose amounts (Calhoun, 2008).  Resistant HTN is a relatively common condition, estimated to affect approximately 30% of the adult population in the United States.  In large clinical trials of HTN treatment, up to 20-30% of participants meet the definition for resistant HTN, and in tertiary care HTN clinics, the prevalence has been estimated to be 11-18% (Acelajado, 2010).

Resistant HTN is associated with a higher risk for adverse outcomes, such as stroke, myocardial infarction (MI), heart failure, and kidney failure.  Notably, resistant HTN is not the same as uncontrolled HTN.  Uncontrolled HTN is a lack of BP control due to factors, such as poor adherence to the medication schedule, insufficient doses of antihypertensive medications, excessive salt or alcohol intake, volume overload, drug-induced HTN, and other forms of secondary HTN, due to comorbid conditions (Doumas, 2010).

RFA for the treatment of HTN is theorized to decrease both the afferent sympathetic signals from the kidneys to the brain and the efferent signals from the brain to the kidneys.  This decreases sympathetic activation, decreases vasoconstriction, and decreases activation of the renin-angiotensin system which potentially lowers the blood pressure (Zile, 2012).

Although to date, no RFA device has been cleared by the U.S. Food and Drug Administration (FDA) for ablation of the renal sympathetic nerves as a treatment for HTN, there are several devices that have been developed for renal sympathetic denervation as a proposed treatment option for resistant HTN.  The EnligHTN Renal Guide Catheter (St. Jude Medical, Plymouth, MN) received clearance from the FDA in 2014 for marketing through the 510(k) process based on substantial equivalence to predicate devices for the following indication: “Percutaneous use through an introducer sheath to facilitate a pathway to introduce interventional and diagnostic devices into the renal arterial vasculature” (FDA, 2014).  The Symplicity Renal Denervation (RDN) System (Medtronic, Inc., Plainfield, IN) was launched commercially in April 2010 and is currently available in countries outside the U.S.  The Symplicity RDN System consists of a flexible catheter for percutaneous use in the renal arteries and an external power generator.  At the present time, the Symplicity RDNSystem is limited to investigational use only in the U.S.  Other similar catheter-based devices with FDA clearance for the same indications include the St. Jude Medical EnligHTN Multi-electrode RDNSystem (St. Jude Medical, Inc., St. Paul, MN) and the Vessix Guide Sheath (Boston Scientific Corp., Maple Grove, MN).

The SYMPLICITY HTN-3 was a Phase 3, single blinded, prospective, sham-controlled, randomized controlled trial (RCT) that was designed to evaluate the safety and effectiveness of renal denervation with the Symplicity RDNSystem in subjects with resistant HTN.  A total of 535 study subjects underwent randomization.  The mean (± standard deviation [SD]) change in systolic blood pressure (SBP) at 6 months was -14.13 ± 23.93 mm Hg in the denervation group, as compared with -11.74 ± 25.94 mm Hg in the sham-procedure group (p<0.001 for both comparisons of the change from baseline), for a difference of -2.39 mm Hg (95% confidence interval [CI], -6.89 to 2.12; p=0.26 for superiority with a margin of 5 mm Hg).  The change in 24-hour ambulatory SBP was -6.75 ± 15.11 mm Hg in the denervation group and -4.79 ± 17.25 mm Hg in the sham-procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; p=0.98 for superiority with a margin of 2 mm Hg).  There were no significant differences in safety between the two groups.  The investigators concluded that this trial did not show a significant reduction in SBP in individuals with resistant HTN 6 months after renal artery denervation, as compared with a sham control (Bhatt, 2014).  Additional articles have been published with up to 12 month results of the SYMPLICITY HTN-3 trial, in which they also concluded that the trial did not demonstrate a benefit from renal artery denervation or reduction in ambulatory SBP in either the 24-hour or day-and-night periods, as compared with sham (Bakris, 2014; Bakris, 2015). 

In January, 2014 Medtronic, Inc. announced that its pivotal trial in the U.S., the SYMPLICITY HTN-3 trial, failed to meet its primary and secondary efficacy end-points, as described above.  As a result, Medtronic intends to formulate a panel of independent advisors made up of physicians and researchers who will be asked to make recommendations about the future of the global HTN clinical trial program, now known as the SPYRAL HTN Global Clinical Program.  This program is described by the manufacturer, Medtronics as, “A multi-phased clinical study strategy aimed to establish the safety and efficacy of renal denervation to lower blood pressure.”  Panel members will also provide advice on continued physician and patient access to the SYMPLICITY technology in countries with regulatory approval for this device.  According to this announcement from Medtronics, pending the panel review determinations, the company will suspend enrollment in the three countries where renal denervation HTN trials were being conducted, as part of the application process for regulatory approval, (which were SYMPLICITY HTN-4 in the U.S., HTN-Japan and HTN-India). In light of the results of the SYMPLICITY HTN-3 trial, Medtronic will discontinue the already suspended SYMPLICITY HTN-4 trial.  Medtronic also announced that it will continue to enroll individuals in the Global SYMPLICITY Registry.

Since results of the SYMPLICITY HTN-3 trial were published, the manufacturer has modified and redesigned the catheter, which is now known as the SYMPLICITY SPYRAL System.  This catheter device now has more electrodes to deliver up to four simultaneous RFAs in a helical pattern, and treatment of branch vessels has been added to the technique.  According to Medtronics, the FDA has provided investigational device exemption (IDE) approval for the two initial trials of the SPYRAL HTN Global Clinical Trial Program which are randomized, sham-controlled studies evaluating the device in up to 433 subjects at 50 sites in the U.S., Europe, Australia, and Japan.

The SPYRAL HTN-OFF MED study (NCT02439749) has primary efficacy and safety endpoints which are 24-hour BP at 3 months and major adverse events through 1 month after randomization, respectively.  The second trial utilized a separate cohort of 80 trial subjects; the SPYRAL HTN ON-MED study (NCT02439775) required eligible subjects to be treated with a consistent medical therapy of up to 3 antihypertensive drugs during the study.  The SPYRAL HTN OFF-MED study included a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications.  In 2017, Townsend and colleagues reported 3-month results of the SPYRAL HTN OFF-MED trial.  This study included subjects with a mean 24-hour ambulatory systolic (SBP) of 140 mm Hg or greater and less than 170 mm Hg at second screening who underwent renal angiography and were randomly assigned to renal denervation or sham control.  Results at 3 months reflected 24-hour ambulatory BP decreased from baseline to 3 months in the renal denervation group (24-hour SBP -5.5 mm Hg [95% CI, -9.1 to -2.0; p=0.0031], and 24-hour diastolic (DBP) -4.8 mm Hg [-7.0 to -2.6; p<0.0001]; office SBP -10.0 mm Hg [-15.1 to -4.9; p=0.0004], and office DBP -5.3 mm Hg [-7.8 to -2.7; p=0.0002]).  No significant changes were seen in the sham-control group (24-hour SBP -0.5 mm Hg [95% CI -3.9 to 2.9; p=0.7644], 24-hour DBP -0.4 mm Hg [-2.2 to 1.4; p=0.6448], and office SBP -2.3 mm Hg [-6.1 to 1.6; p=0.2381], and office DBP -0.3 mm Hg [-2.9 to 2.2; p=0.8052]).  The mean difference between the groups favored renal denervation for 3 month change in both office and 24-hour BP from baseline: 24-hour SBP -5.0 mm Hg (95% CI -9.9 to -0.2; p=0.0414), 24-hour DBP -4.4 mm Hg (-7.2 to -1.6; p=0.0024), office SBP -7.7 mm Hg (-14.0 to -1.5; p=0.0155), and office DBP -4.9 mm Hg (-8.5 to -1.4; p=0.0077). There were no major adverse events in either group (Townsend, 2017). 

In the SPYRAL HTN-ON MED trial, 80 subjects with uncontrolled HTN (office SBP, 150–180 mm Hg; DBP, 90 mm Hg or higher) were randomized to renal denervation with RFA or a sham procedure with angiography.  Trial participants were taking up to 3 antihypertensive drugs.  Office and 24 hour ambulatory BP decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 hour SBP -7.0 mm Hg, 95% CI, -12.0 to -2.1; p=0.0059, 24 hour DBP -4.3 mm Hg, -7.8 to -0.8; p=0.0174, office SBP -6.6 mm Hg, -12.4 to -0.9; p=0.0250, and office DBP -4.2 mm Hg, -7.7 to -0.7; p=0.0190).  The change in BP was significantly greater at 6 months in the renal denervation group than the sham-control group for office SBP (difference -6.8 mm Hg, 95% CI, -12.5 to -1.1; p=0.0205), 24 hour SBP (difference -7.4 mm Hg, -12.5 to -2.3; p=0.0051), office DBP (difference -3.5 mm Hg, -7.0 to -0.0; p=0.0478), and 24 hour DBP (difference -4.1 mm Hg, -7.8 to -0.4; p=0.0292).  Evaluation of hourly changes in 24 hour SBP and DBP showed BP reduction throughout 24 hours for the renal denervation group.  At 3 months, BP reductions were not significantly different between groups.  It was also noted that medication adherence was about 60% and varied for individual trial subjects throughout the study.  No major adverse events were recorded in either group (Kandzari, 2018).  The primary estimated completion dates for these two trials are as follows:  for SPYRAL HTN ON-MED study – January 2021; SPYRAL HTN OFF-MED study – June 2020.

Additional studies have investigated confounding factors that potentially affected the early results of RFA trials.  In 2016, the DENERHTN trial (Renal Denervation for Hypertension) attempted to report the influence of adherence to antihypertensive treatment regimens on BP control.  Individual adherence to antihypertensive medical treatment was evaluated at 6 months with drug screening of urine and plasma samples from 85 trial subjects.  The numbers of trial subjects who were fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent (7/40 versus 4/45) to antihypertensive treatment did not differ significantly in the renal denervation and the control groups, respectively (p=0.3605).  The difference noted in the change in daytime ambulatory SBP from baseline to 6 months between the 2 groups was -6.7 mm Hg (p=0.0461) in the fully adherent and -7.8 mm Hg (p=0.0996) in the nonadherent group (made up of the partially nonadherent plus the completely nonadherent).  The between-subject variability in daytime ambulatory SBP was greater for the nonadherent than for the fully adherent subjects.  The authors concluded that the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%), but not different in the renal denervation and control groups.  Regardless of adherence to medical treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in BP than with standardized antihypertensive medical treatment alone.  The number of responders was greater in the denervation group (20/44, 44.5%) than in the control group (11/53, 20.8%; p=0.01).  In the discriminant analysis, baseline average nighttime SBP and standard deviation were significant predictors of the SBP response in the denervation group only, allowing adequate responder classification of 70% of the trial participants.  According to the investigators, this analysis indicated that denervation lowers ambulatory BP homogeneously over 24 hours in subjects with resistant HTN which suggests that nighttime SBP and variability are predictors of the BP response to denervation (Azizi, 2016; Gosse, 2017).

Results of a prior small, short-term, RCT, the Symplicity HTN-2 trial, were published in 2010.  This trial evaluated renal sympathetic denervation using the Symplicity Renal Denervation System versus standard pharmacologic treatment for a total of 106 subjects with resistant HTN (defined as having an SBP of at least 160 mm Hg despite regimens of three or more antihypertensive medications).  The trial was unblinded, and subjects were followed for 6 months with a primary endpoint of between-group differences in the change in BP over the course of the 6-month trial.  Secondary outcomes included a composite outcome of adverse cardiovascular events and adverse effects of treatment.  Baseline BP was 178/98 in the RFA treatment group and 178/97 in the control group treated with medications alone.  At 6 months, the BP reductions in the RFA group were 32 mm Hg systolic (SD of 23) and 12 mm Hg diastolic (SD of 11).  In the control group, there was a 1 mm Hg increase in SBP and no change for diastolic BP (p<0.0001 for both SBP and SBP differences).  The percent of subjects who achieved an SBP of 140 mm or less was 39% (19/49) in the RFA group compared to 6% (3/51) in the control group (p<0.0001).  There was no difference in renal function, as measured by serum creatinine, between groups at the 6-month follow-up time. In the RFA group, 3 subjects reported an adverse cardiovascular event compared to 2 in the control group (p=nonsignificant).  Other serious adverse events requiring admission in the RFA group included 1 case each of nausea/vomiting, hypertensive crisis, transient ischemic attack (TIA), and hypotension.  In each group, 3 subjects were lost to follow-up.  It was noted that larger studies with longer outcomes data are needed to demonstrate the safety and efficacy of RFA of the renal nerves as a treatment of resistant HTN.  The additional issue of durability of treatment effect also warrants investigation, due to the potential for post-treatment re-innervation of the treated renal nerves which could potentially result in diminished therapeutic effect over time following the RFA procedure (Esler, 2010). 

Follow-up outcomes data at 36 months were reported in 2014 in 40 of 52 subjects in the initial renal denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal denervation at 6 months.  Baseline BP was 184 ± 19/99 ± 16 mm Hg in all treated subjects.  At 30 months post-procedure, SBP decreased 34 mm Hg (95% CI: -40, -27; p<0.01) and diastolic BP decreased 13 mm Hg (95% CI: -16, -10; p<0.01).  The systolic and diastolic BP reduction at 36 months for the initial renal denervation group was -33 mm Hg (95% CI: -40, -25; p<0.01) and -14 mm Hg (95% CI: -17, -10; p<0.01), respectively.  Procedural complications included one hematoma, and one renal artery dissection before energy delivery that was treated successfully.  Later complications included 2 cases of acute renal failure, which fully resolved, 15 hypertensive events requiring hospitalization, and 3 deaths that were deemed unrelated to the device or the therapy.  The authors concluded that renal denervation resulted in sustained lowering of BP at 3 years in a selected population of subjects with severe, treatment-resistant HTN without serious safety concerns.  These longer term findings were limited by the lack of comparison to a control group, due to the crossover design (Esler, 2014).

In 2016, the Agency for Healthcare Research and Quality (AHRQ) issued a technical brief with results of a systematic review of the literature to assess the effectiveness of renal denervation in the Medicare population.  This report was conducted by the Johns Hopkins University Evidence-based Practice Center at the request of the Centers for Medicare and Medicaid Services (CMS).  Data was abstracted from 83 studies (n=7660); 9 were RCTs, 8 were comparative cohorts, and 66 were non-comparative cohorts.  It was noted that the trial participants within the included studies were only partially comparable to the Medicare-eligible population, due to the multifactorial causes of treatment-resistant HTN.  Additional limitations of the literature review included variable eligibility criteria between the studies, the fact that adherence to diet and medications was not routinely assessed in all the studies, and only 10 (12%) of all studies described a run-in period prior to randomization.  None of the studies were designed or powered to detect a long-term difference between groups in clinical endpoints, such as stroke, myocardial infarction, hospitalization, or mortality, and few studies reported these outcomes.  Also beneficial clinical effects of renal denervation by specific subgroups (age, gender, race/ethnicity) were seldom and inconsistently reported.  Details about different denervation techniques used and interventionalist training and experience were not uniformly reported.  Only 6-month outcomes data was reported in the majority of included studies.  The technical brief provided the following conclusions:

Limited evidence suggests that renal denervation in patients with treatment-resistant HTN lowers systolic BP, but the results were highly variable and the studies reviewed were not designed to determine improvement in clinical endpoints. The most rigorously conducted RCTs showed much smaller BP reductions, as compared with observational non-comparative studies. Further research is needed to identify optimal candidates for renal denervation, refine next generation renal denervation technology, develop methods for assessing completeness of renal denervation procedures, and demonstrate the efficacy of renal denervation in reducing BP and improving clinical endpoints, including the risk of stroke, myocardial infarction, heart failure, and death in patients with HTN (Shafi, AHRQ, 2016).

Despite some favorable results for renal denervation as treatment of drug-resistant uncontrolled HTN from recent trials, additional studies with large numbers of participants and longer term outcomes data are warranted to more fully demonstrate and confirm the safety and efficacy of RFA of the renal sympathetic nerves and the long term impact on clinical outcomes.  There are multiple additional interventional trials in progress and ongoing RCTs of new renal denervation catheters as a treatment for resistant HTN (Azizi, 2018; de Jager, 2017; Kandzari, 2016; Mauri, 2018).

Background/Overview

RFA of the sympathetic renal nerves 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.  It is anticipated that this procedure will be performed on an outpatient basis with the use of appropriate anesthesia.  Potential complications of this procedure include, but are not limited to, vascular access problems, perforation of the renal artery and renal artery stenosis.  Additional information is needed from the clinical trials currently in progress regarding the safety and efficacy associated with RFA of the renal nerves.

Definitions

Radiofrequency ablation (RFA):  This minimally invasive surgical procedure utilizes low power radiofrequency energy to ablate (or destroy) various tissues of the body. 

Resistant hypertension (HTN):  Blood pressure (BP) above goal despite treatment with three antihypertensive agents, of different classes ideally including a diuretic, all prescribed at optimal dose amounts.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

CPT

 

0338T

Transcatheter renal sympathetic denervation, percutaneous approach including arterial puncture, selective catheter placement(s) renal artery(ies), fluoroscopy, contrast injection(s), intraprocedural roadmapping and radiological supervision and interpretation, including pressure gradient measurements, flush aortogram and diagnostic renal angiography when performed; unilateral

0339T

Transcatheter renal sympathetic denervation, percutaneous approach including arterial puncture, selective catheter placement(s) renal artery(ies), fluoroscopy, contrast injection(s), intraprocedural roadmapping and radiological supervision and interpretation, including pressure gradient measurements, flush aortogram and diagnostic renal angiography when performed; bilateral

 

 

ICD-10 Procedure

 

 

For the following codes when specified as ablation (or destruction) of renal sympathetic nerves:

015L3ZZ

Destruction of thoracic sympathetic nerve, percutaneous approach

015M3ZZ

Destruction of abdominal sympathetic nerve, percutaneous approach

015N3ZZ

Destruction of lumbar sympathetic nerve, percutaneous approach

 

 

ICD-10 Diagnosis

 

 

All diagnoses

References

Peer Reviewed Publications:

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  3. Azizi M, Sapoval M, Gosse P, et al. Renal Denervation for Hypertension (DENERHTN) investigators. Optimum and stepped care standardized antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicenter, open-label, randomized controlled trial. Lancet. 2015; 385(9981):1957-1965.
  4. Azizi M, Schmieder RE, Mahfoud F, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicenter, international, single-blind, randomized, sham-controlled trial. Lancet. 2018; 391(10137):2335-2345.
  5. Bakris GL, Townsend RR, Flack JM, et al; SYMPLICITY HTN-3 Investigators. 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial. J Am Coll Cardiol. 2015; 65(13):1314-1321.
  6. Bakris GL, Townsend RR, Liu M, et al. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. J Am Coll Cardiol. 2014; 64(11):1071-1078.
  7. Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014; 370(15):1393-1401.
  8. Brandt MC, Mahfoud F, Reda S, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012; 59(10):901-909.
  9. de Jager RL, de Beus E, Beeftink MM, et al. Impact of medication adherence on the effect of renal denervation: The SYMPATHY trial. Hypertension. 2017; 69(4):678-684.
  10. Doumas M, Papademetriou V, Douma S, et al. Benefits from treatment and control of patients with resistant hypertension. Int J Hypertens. 2010; 2011:318549.
  11. Esler MD, Bohm M, Sievert H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J. 2014; 35(26):1752-1759.
  12. Esler MD, Krum H, Schlaich M, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: One-year results from the Symplicity HTN-2 randomized, controlled trial. Circulation. 2012; 126(25):2976-2982.
  13. Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomized controlled trial. Lancet. 2010; 376(9756):1903-1909.
  14. Fadl Elmula FE, Hoffmann P, Larstorp AC, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014; 63(5):991-999.
  15. Fadl Elmula FE, Jin Y, Yang WY, et al. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension. Blood Press. 2015; 24(5):263-274.
  16. Fengler K, Heinemann D, Okon T, et al. Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial. Clin Res Cardiol. 2016; 105(7):592-600.
  17. Flack JM, Bhatt DL, Kandzari DE, et al. An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial. J Am Soc Hypertens. 2015; 9(10):769-779.
  18. Gosse P, Cremer A, Pereira H, et al. Twenty-four-hour blood pressure monitoring to predict and assess impact of renal denervation: The DENERHTN Study (Renal Denervation for Hypertension). Hypertension. 2017; 69(3):494-500.
  19. Hering D, Marusic P, Walton AS, et al. Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension. Int J Cardiol. 2016; 202:388-393.
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  21. Kandzari DE, Bhatt DL, Brar S, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J. 2015; 36(4):219-227.
  22. Kandzari DE, Bhatt DL, Sobotka PA, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial. Clin Cardiol. 2012; 35(9):528-535.
  23. 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 randomized trial. Lancet. 2018; 391(10137):2346-2355.
  24. 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. 2016; 171(1):82-91.
  25. Krum H, Barman N, Schlaich M, et al. Long-term follow up of catheter-based renal sympathetic denervation for resistant hypertension confirms durable blood pressure reduction. J Am Coll Cardiol. 2012; 59(13s1):E1704–E1704.
  26. Krum H, Schlaich MP, Sobotka PA, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2014; 383(9917):622-629.
  27. Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicenter safety and proof-of-principle cohort study. Lancet. 2009; 373(9671):1275-1281.
  28. Kwok CS, Loke YK, Pradhan S, et al. Renal denervation and blood pressure reduction in resistant hypertension: a systematic review and meta-analysis. Open Heart. 2014; 1(1):e000092.
  29. Mahfoud F, Cremers B, Janker J, et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012; 60(2):419-424.
  30. Mathiassen ON, Vase H, Bech JN, et al. Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial. J Hypertens. 2016; 34(8):1639-1647.
  31. Mauri L, Kario K, Basile J, et al. A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs. Am Heart J. 2018; 195:115-129.
  32. Oliveras A, Armario P, Clara A, et al. Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study - a randomized controlled trial. J Hypertens.  2016; 34(9):1863-1871.
  33. Schneider S, Promny D, Sinnecker D, et al. Impact of sympathetic renal denervation: a randomized study in patients after renal transplantation (ISAR-denerve). Nephrol Dial Transplant. 2015; 30(11):1928-1936.
  34. Shantha GP, Pancholy SB. Effect of renal sympathetic denervation on apnea-hypopnea index in patients with obstructive sleep apnea: a systematic review and meta-analysis. Sleep Breath. 2015; 19(1):29-34.
  35. Sun D, Li C, Li M, et al. Renal denervation vs pharmacotherapy for resistant hypertension: a meta-analysis. J Clin Hypertens (Greenwich). 2016; 18(8):733-740.
  36. Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011; 57(5):911-917.
  37. 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 randomized, sham-controlled, proof-of-concept trial. Lancet. 2017; 390(10108):2160-2170.
  38. Ukena C, Mahfoud F, Kindermann I, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol. 2011; 58(11):1176-1182.
  39. Witkowski A, Prejbisz A, Florczak E, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011; 58(4):559-565.
  40. Worthley SG, Wilkins GT, Webster MW, et al. Safety and performance of the second generation EnligHTN Renal Denervation System in patients with drug-resistant, uncontrolled hypertension. Atherosclerosis. 2017; 262:94-100.
  41. Yao Y, Zhang D, Qian J, et al. The effect of renal denervation on resistant hypertension: Meta-analysis of randomized controlled clinical trials. Clin Exp Hypertens. 2016; 38(3):278-286.
  42. Zile MR, Little WC. Effects of autonomic modulation: more than just blood pressure. J Am Coll Cardiol. 2012; 59(10):910-912.
  43. Zhang X, Wu N, Yan W, et al. The effects of renal denervation on resistant hypertension patients: a meta-analysis. Blood Press Monit. 2016; 21(4):206-214.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Calhoun DA, Jones D, Textor S, et al. 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. Hypertension. 2008; 51(6):1403-1419.
  2. Lackland DT, Allison M, Aronow WS, et al. American Heart Association (AHA) Expert Consensus new recommendations for treating patients with high blood pressure and cardiovascular disease. March 31, 2015. Available at: http://newsroom.heart.org/news/new-recommendations-for-treating-patients-with-high-blood-pressure-and-cardiovascular-disease. Accessed on August 21, 2018.
  3. Lobo MD, de Belder MA, Cleveland T, et al. Joint UK societies' 2014 consensus statement on renal denervation for resistant hypertension. Heart. 2015; 101(1):10-16.
  4. Mahfoud F, Lüscher TF, Andersson B, et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J. 2013; 34(28):2149-2157.
  5. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013; 31(7):1281–1357.  Available at: http://eurheartj.oxfordjournals.org/content/34/28/2159. Accessed on August 22, 2018.
  6. Medtronic Vascular. SPYRAL HTN-ON MED Study. NLM Identifier NCT02439775. Last updated April 17, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02439775. Accessed on August 20, 2018.
  7. Medtronic Vascular. SPYRAL HTN-OFF MED Study. NLM Identifier NCT02439749. Last updated August 22, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02439749. Accessed on August 22, 2018.
  8. Rosendorff C, Lackland DT, Allison M, et al. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Circ. 2015; 131(19):e435-470.
  9. Schmieder RE, Redon J, Grassi G, et al.  European Society of Hypertension (ESH) position paper: renal denervation - an interventional therapy of resistant hypertension.  J Hypertens. 2012; 30(5):837-841.
  10. Shafi T, Chacko M, Berger Z, et al. Renal Denervation in the Medicare Population. Technology Assessment Program Project ID: RENT1115. (Prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-2015-00006-I) Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); July 2016. Available at: http://www.ahrq.gov/research/findings/ta/index.html. Accessed on August 21, 2018.
  11. U.S. Food and Drug Administration (FDA). 510(k) Premarket Notification Database. The EnligHTN Renal Guide Catheter (St. Jude Medical, Plymouth, MN). Summary of Safety and Effectiveness. No. K131592. Rockville, MD: FDA. January 31, 2014. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf13/k131592.pdf. Accessed on August 21, 2018.
  12. U.S. Food and Drug Administration (FDA). 510(k) Premarket Notification Database.  The Vessix Guide Sheath (Boston Scientific Corp., Maple Grove, MN). Summary of Safety and Effectiveness. No. K140641. Rockville, MD: FDA. July 3, 2014. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf14/k140641.pdf. Accessed on August 21, 2018.
Websites for Additional Information
  1. Additional information about high blood pressure from the American Heart Association. Available at:  http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/High-Blood-Pressure_UCM_002020_SubHomePage.jsp. Accessed on August 21, 2018.
  2. Information on the Symplicity Renal Denervation System is available on the manufacturer’s web site, Medtronic, Inc. Available at:  http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=1802710. Accessed on August 21, 2018.
Index

Ablation, Radiofrequency
Biosense Webster Thermocouple Catheter
Hypertension, Resistant
Radiofrequency Ablation (RFA)
St. Jude Medical EnligHTN
Sympathetic Renal Nerves
Symplicity Renal Denervation (RDN) System
SYMPLICITY SPYRAL System
Vessix Guide Sheath

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed

09/13/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. The Rationale and References sections were updated.

Reviewed

11/02/2017

MPTAC review. The document header wording was updated from “Current Effective Date” to “Publish Date.” The Rationale and References sections were updated.

Reviewed

11/03/2016

MPTAC review. Updated Rationale and References sections. 

Reviewed

11/05/2015

MPTAC review. The Rationale and References were updated.  Removed ICD-9 codes from Coding section.

Reviewed

11/13/2014

MPTAC review. The Rationale and References were updated. 

Reviewed

11/14/2013

MPTAC review. The Rationale and References were updated. Updated Coding section with 01/01/2014 CPT changes.

New

11/08/2012

MPTAC review. Initial document development.