Carotid Sinus Stimulation for Hypertension

Number: 0820

Policy

Aetna considers implantable carotid sinus stimulators (e.g., the Barostim neo™ System, and the Rheos Baroreflex Hypertension Therapy System) experimental and investigational for the treatment of hypertension and for all other indications (e.g., heart failure) because its effectiveness has not been established.

Background

Hypertension is a major cause of morbidity and mortality in the United States.  Despite the availability of potent anti-hypertensive medications, many patients remain hypertensive.  Thus, non-pharmacological therapies have been attracting more interest.  Electrical stimulation (ES) of the carotid sinus has been shown to lowers blood pressure (BP) by activating the baroreflex and thereby reducing sympathetic tone.  The arterial baroreflex regulates mean arterial pressure by responding automatically to changes in cardiac output and vessel tone via baroreceptors, which monitor arterial pressure by gauging the degree of stretch in vessel walls.  Baroreceptors are located in the walls of the aorta and carotid arteries, with a concentration of receptors located within the carotid sinus.  Activation of baroreceptors produces immediate responses in cardiovascular sympathetic and cardiac parasympathetic nerves to adjust heart rate (HR), stroke volume, vasoconstriction, as well as fluid excretion.  These actions raise or lower BP as needed.

The Rheos Baroreflex Hypertension Therapy System (CVRx, Inc., Minneapolis, MN) is an implantable device for the treatment of patients with drug-resistant hypertension (i.e., the hypertensive state characterized by the inability of multiple anti-hypertensive drug interventions to lower BP to goal levels) who have a systolic BP (SBP) of greater than or equal to 160 mm Hg.  It is reported to reduce BP by activating the baroreflex through ES of baroreceptors in the carotid sinus.  The Rheos Baroreflex Hypertension Therapy System has 3 major components:

• An implantable pulse generator (IPG)
• Carotid sinus leads (CSLs)
• A programmer system.

The pulse generator is implanted subcutaneously near the collarbone.  The CSLs are placed on the carotid arteries and run subcutaneously to the pulse generator (Note: the procedure does not involve carotid dissection).  The operation usually takes about 2 to 3 hours.  After implantation, a continuous mild electrical pulsation stimulates baroreceptors to produce a reflexive reduction in BP.  The IPG provides control and delivery of activation energy through the CSLs.  The leads conduct activation energy from the IPG to target receptors in the left and right carotid arteries.  The programmer system provides the ability to communicate non-invasively with the IPG after implantation to modulate the frequency and intensity of ES.

In a phase II clinical trial, Illig et al (2006) evaluated the response of patients with multidrug-resistant hypertension to ES of the carotid sinus via an implantable device.  The system consists of an IPG with bilateral peri-vascular CSLs.  Implantation was performed bilaterally with patients under narcotic anesthesia.  Dose-response testing at 0 to 6 V was assessed before discharge and at monthly intervals thereafter; the device was activated after 1 month's recovery time.  This was a Food and Drug Administration-monitored phase II trial performed at 5 centers in the United States.  A total of 10 patients with resistant hypertension (taking a median of 6 anti-hypertensive medications) underwent implantation.  All 10 were successful, with no significant morbidity.  The mean procedure time was 198 minutes.  There were no adverse events attributable to the device.  Pre-discharge dose-response testing revealed consistent (r = 0.88) reductions in SBP of 41 mm Hg (mean fall is from 180 to 139 mm Hg), with a peak response at 4.8 V (p < 0.001) and without significant bradycardia or bothersome symptoms.  The authors concluded that a surgically implantable device for ES of the carotid baroreflex system can be placed safely and produces a significant acute decrease in BP without significant side effects.

Tordoir et al (2007) examined peri-operative outcomes and BP responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of drug-resistant hypertension.  These investigators reported on the first 17 patients enrolled in a multi-center study.  Bilateral peri-vascular CSLs and a IPG are permanently implanted.  Optimal placement of the CSL is determined by intra-operative BP responses to test activations.  Acute BP responses were tested post-operatively and during the first 4 months of follow-up.  Prior to implant, BP was 189.6 +/- 27.5 (SBP)/110.7 +/- 15.3 (diastolic BP [DBP]) mm Hg despite stable therapy (5.2 +/- 1.8 anti-hypertensive drugs).  The mean procedure time was 202 +/- 43 minutes.  No peri-operative strokes or deaths occurred.  System tests performed 1 or up to 3 days post-operatively resulted in significant (all p < or = 0.0001) mean maximum reduction, with standard deviations and 95 % confidence limits for SBP, DBP and HR of 28 +/- 22 (17, 39) mm Hg, 16 +/- 11 (10, 22) mm Hg and 8 +/- 4 (6, 11) beats/min, respectively.  Repeated testing during 3 months of therapeutic electrical activation demonstrated a durable response.  The authors concluded that these preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.

Heusser et al (2010) tested the hypothesis that ES of carotid baroreceptors acutely reduces sympathetic vasomotor tone and BP in patients with drug-resistant arterial hypertension.  Furthermore, these researchers tested whether ES impairs the physiological baroreflex regulation.  They studied 7 men and 5 women (aged 43 to 69 years) with drug-resistant arterial hypertension.  A bilateral electric baroreflex stimulator at the level of the carotid sinus (Rheos) was implanted greater than or equal to 1 month before the study.  Intra-arterial BP, HR, muscle sympathetic nerve activity (micro-neurography), cardiac baroreflex sensitivity (cross-spectral analysis and sequence method), sympathetic baroreflex sensitivity (threshold technique), plasma renin, and norepinephrine concentrations were measured.  Measurements were performed under resting conditions, with and without electric baroreflex stimulation, for greater than or equal to 6 minutes during the same experiment.  Intra-arterial BP was 193 +/- 9/94 +/- 5 mm Hg on medications.  Acute electric baroreflex stimulation decreased SBP by 32 +/- 10 mm Hg (range of +7 to -108 mm Hg; p = 0.01).  The depressor response was correlated with a muscle sympathetic nerve activity reduction (r(2) = 0.42; p < 0.05).  In responders, muscle sympathetic nerve activity decreased sharply when ES started.  Then, muscle sympathetic nerve activity increased but remained below the baseline level throughout the stimulation period.  Heart rate decreased 4.5 +/- 1.5 beats/min with ES (p < 0.05).  Plasma renin concentration decreased 20 +/- 8 % (p < 0.05).  Electrical stimulation of carotid sinus baroreflex afferents acutely decreased arterial BP in hypertensive patients, without negative effects on physiological baroreflex regulation.  The depressor response was mediated through sympathetic inhibition.

Sanchez et al (2010) evaluated carotid artery structural integrity after implantation of the CSLs.  A total of 29 CSLs were implanted on the common carotid arteries of 8 sheep.  The studies were terminated at 3 and 6 months post-implantation to assess anatomical and histological changes.  Additionally, 10 patients with resistant hypertension were enrolled in the Rheos Multicenter Feasibility Trial.  Duplex ultrasound (DUS) was performed before device implantation and at 1 and 4 months post-implantation in this patient cohort.  An independent core laboratory assessed all DUSs.  Ovine carotid angiography revealed no significant stenoses, while anatomical and histological evaluations demonstrated electrode encapsulation in a thin layer of connective tissue with no evidence of stenosis, erosion, or inflammation.  Duplex ultrasound evaluation revealed no significant increase in peak systolic velocities of the common and internal carotid arteries 1 and 4 months after initial implantation, indicating a lack of injury, remodeling, or stenosis.  The authors concluded that the current data suggested that the CSLs used with the Rheos System are not associated with the development of carotid stenosis or injury.  These short-term data support the concept of CSL placement and merit long-term investigation in a larger multi-center prospective trial.

In a prospective, non-randomized, feasibility study, Scheffers et al (2010) examined the safety and efficacy of Rheos therapy in drug-resistant hypertension patients.  A total of 45 subjects with SBP greater than or equal to 160 mm Hg or DBP greater than or equal to 90 mm Hg despite at least 3 anti-hypertensive drugs were enrolled in this study.  Subjects were followed-up for as long as 2 years.  An external programmer was used to optimize and individualize efficacy.  Baseline mean BP was 179/105 mm Hg and HR was 80 beats/min, with a median of 5 anti-hypertensive drugs.  After 3 months of device therapy, mean BP was reduced by 21/12 mm Hg.  This result was sustained in 17 subjects who completed 2 years of follow-up, with a mean reduction of 33/22 mm Hg.  The device exhibited a favorable safety profile.  The authors concluded that the Rheos device sustainably reduces BP in drug-resistant hypertensive subjects with multiple co-morbidities receiving numerous medications.  They stated that this novel approach holds promise for patients with drug-resistant hypertension and is currently under evaluation in a prospective, placebo-controlled clinical trial.

Doumas et al (2009) stated that the role of the carotid baroreflex in BP regulation has been known for a long time but its effects were thought to be short-lived.  Recent data indicate that stimulation of carotid baroreceptors may lower BP not only for short periods of time, but also in the long run.  Recent advances in technology permitted the development of a new device (Rheos) that addresses problems with older devices.  Several questions remain to be addressed before Rheos can be used widely, and several potential clinical applications remain to be clarified.  The authors stated that the carotid baroreceptor reflex is probably not completely in control of BP.  Baroreflexes are one of many control systems acting in concert.  Joshi and associates (2009) stated that ES of the carotid sinus baroreceptor through a surgically implanted device is currently under clinical investigation and is showing some encouraging early results.  Furthermore, Lovett et al (2009) noted that chronic results from feasibility studies indicated that Rheos therapy has an acceptable safety profile and may lead to long-term control of BP in drug-resistant hypertensive patients.  Other effects include significant reductions in left ventricular mass and left atrial size.  The spectrum of therapeutic impact suggests that Rheos therapy may improve long-term outcomes in drug-resistant hypertension and possibly benefit related populations.  They noted that larger randomized, controlled trials are ongoing to verify chronic benefits.

Grassi et al (2010) stated that drug-resistant hypertension represents a condition frequently detected in clinical practice.  Its main features are represented by its heterogeneous etiology as well as its very high cardiovascular risk.  This latter peculiarity has implemented the research for new approaches to the treatment of the disease.  These researchers discussed 2 of these approaches: (i) carotid baroreceptor ES and (ii) the renal denervation procedure.  They stated that clinical studies and large-scale clinical trials are presently ongoing with the aim of defining the long-term safety and effectiveness of the 2 interventions.  Taylor and Bisognano (2010) stated that chronic baroreceptor ES of the carotid sinus has been shown to reduce BP by inhibiting the sympathetic nervous system, especially the renal sympathetic tone.  This finding has led to the development of implantable carotid sinus stimulators, which have now been studied in both animals and humans, as a means for treating chronic hypertension.  The enthusiasm for this modality has led to ongoing studies, which will provide more information on its safety and effectiveness in patients with drug-resistant hypertension.  The early study results using baroreflex ES therapy are promising and suggest that it may play a significant role in controlling BP in the future.  Kougias et al (2010) stated that a model of ES of the carotid sinus has been developed and successfully tested in animals.  Following these encouraging results, human trials to evaluate the clinical application of electrical carotid sinus manipulation in the treatment of systemic hypertension have commenced, and results so far indicated that this represents an exciting potential tool in the clinician's armament against chronic arterial hypertension.

Lohmeier and Iliescu (2011) summarized the pre-clinical studies that have provided insight into the mechanisms that account for the chronic BP-lowering effects of carotid baroreflex activation.  Some of the mechanisms identified were predictable and confirmed by experimentation.  Others have been surprising and controversial, and resolution will require further investigation.  They stated that although feasibility studies have been promising, firm conclusions regarding the value of this device-based therapy for the treatment of drug-resistant hypertension awaits the results of current multi-center trials.  Ng and colleagues (2011) noted that the Rheos Baroreflex Hypertension Therapy System is a new implantable device that can treat patients with hypertension resistant to multi-drug therapy, by activating the carotid baroreflex through ES of the carotid sinus wall.  Recent studies in both normotensive and hypertensive canine models have reported sustained and clinically relevant reductions in arterial pressure and sympathetic activity with prolonged baroreflex activation.  Clinical trials designed to evaluate the safety and effectiveness of this therapy in patients with drug-resistant hypertension, are now ongoing in both Europe and the United States.

Bisognano et al (2011) examined the effect of baroreflex activation therapy (BAT) on SBP in patients with resistant hypertension.  This was a double-blind randomized trial of 265 subjects with resistant hypertension implanted and subsequently randomized (2:1) 1 month after implantation.  Subjects received either BAT (group A) for the first 6 months or delayed BAT initiation following the 6-month visit (group B).  The 5 co-primary endpoints were: (i) acute SBP responder rate at 6 months; (ii) sustained responder rate at 12 months; (iii) procedure safety; (iv) BAT safety; and (v) device safety.  The trial showed significant benefit for the endpoints of sustained efficacy, BAT safety, and device safety.  However, it did not meet the endpoints for acute responders or procedural safety.  A protocol-specified ancillary analysis showed 42 % (group A) versus 24 % (group B) achieving SBP less than or equal to 140 mm Hg at 6 months (p = 0.005), with both groups achieving over 50 % at 12 months, at which point group B had received 6 months of BAT.  The authors concluded that a clinically meaningful measure, those achieving a SBP of less than or equal to 140 mm Hg, yielded a significant difference between the groups.  The weight of the overall evidence suggested that over the long-term, BAT can safely reduce SBP in patients with resistant hypertension.  They stated that future clinical trials will address the limitations of this study and further define the therapeutic benefit of BAT.

In a single-arm, open-label study, Hoppe and associates (2012) evaluated the effectiveness of the Barostim neo™ system, a 2nd-generation system for delivering BAT.  Subjects were patients with resistant hypertension (SBP greater than or equal to 140 mm Hg despite treatment with 3 or more medications, including 1 ore more diuretic).  Stable medical therapy was required for 4 or more weeks before establishing pre-treatment baseline by averaging 2 SBP readings taken 24 or more hours apart.  A total of 30 patients enrolled from 7 medical centers in Europe and Canada.  From a baseline of 171.7 +/- 20.2/99.5 +/- 13.9 mm Hg, arterial BP decreased by 26.0 +/- 4.4/12.4 +/- 2.5 mm Hg at 6 months.  In a subset (n = 6) of patients with prior renal nerve ablation, arterial BP decreased by 22.3 +/- 9.8 mm Hg.  Background medical therapy for hypertension was unchanged during follow-up.  Three minor procedure-related complications occurred within 30 days of implant.  All complications resolved without sequelae.  The authors concluded that BAT delivered with the 2nd-generation system significantly lowers BP in resistant hypertension with stable, intensive background medical therapy, consistent with studies of the 1st-generation system for electrical activation of the baroreflex, and provides a safety profile comparable to a pace-maker.  The findings of this small open-label study need to be validated by well-designed studies.

Jordan et al (2012) noted that recently, a novel implantable device was developed that produces an electrical field stimulation of the carotid sinus wall.  Carefully conducted experiments in dogs provided important insight in mechanisms mediating the depressor response to electrical carotid sinus stimulation.  Moreover, these studies showed that the treatment success may depend on the underlying pathophysiology of the hypertension.  The authors stated that clinical studies suggested that electrical carotid sinus stimulation attenuates sympathetic activation of vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus lowering BP; however, not all patients respond to treatment.  They concluded that additional clinical trials are needed to ascertain the effectiveness of electrical carotid sinus stimulation in treatment resistant arterial hypertension.

Jordan et al (2013) stated that hypertension is the primary risk factor for cardiovascular and renal-disease endpoints.  Medications help many patients but not all.  Recently, 2 device-related treatments have been introduced, catheter-based renal denervation and electrical carotid sinus stimulation.  Remuneration for these treatments is guaranteed in many countries even though basic information is missing.  These investigators drew attention to deficiencies in the database.  For catheter-based renal denervation, few large-animal data are available to investigate the effect of the intervention on the histology of the arterial wall.  No functional data are available regarding re-innervation.  For carotid sinus stimulation, the situation is similar.  The authors concluded that acute activation of either treatment seems to reduce sympathetic tone dramatically; however, whether or not the effects are sustained over time is unknown.  They stated that no “end-point” data are available for either treatment, and devices should be subjected to evidence-based standards before widespread introduction.

Chobanyan-Jurgens et al (2015) stated that treatment-resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term BP control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced BP in a controlled clinical trial but nevertheless failed to meet the primary efficacy end-point. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in BP with the second-generation device. The authors hoped that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Moreover, these researchers noted that it is important to find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation.

Victor (2015) noted that arterial baroreceptors are mechano-sensitive sensory nerve endings in the walls of the carotid sinuses and aortic arch that buffer the increases and decreases in arterial BP. Electrical field stimulation of the carotid sinus, known as carotid baroreflex activation therapy, holds promise as a novel device-based intervention to supplement, but not replace, drug therapy for patients with resistant hypertension. Acute electrical field stimulation of even 1 carotid sinus can cause a sufficiently large reflex decrease in BP to overcome off-setting reflexes from the contralateral carotid baroreceptors and aortic baroreceptors that are not paced. However, the initial phase III Rheos Pivotal Trial on continuous carotid baroreceptor pacing for resistant hypertension with the first-generation baroreceptor pacemaker yielded equivocal data on efficacy and adverse effects due to facial nerve injury during surgical implantation. A miniaturized second-generation pacing electrode has seemingly overcome the safety issue, and early results with the new device suggested efficacy of unilateral carotid sinus stimulation in HF. The authors stated that a phase III clinical trial of this new device for resistant hypertension has been registered.

Other Indications: 

Georgakopoulos et al (2011) stated that heart failure with preserved ejection fraction (HFpEF) is a substantial public health issue, equal in magnitude to heart failure with reduced ejection fraction.  Clinical outcomes of HFpEF patients are generally poor, and no therapy has been shown to be effective in randomized clinical trials.  Baroreflex activation therapy (BAT) produced by stimulating the carotid sinuses using the Rheos device is being studied for the treatment of hypertension, the primary co-morbidity of HFpEF.  Other potential benefits include regression of left ventricular hypertrophy, normalization of the sympatho-vagal balance, inhibition of the renin-angiotensin-aldosterone system, arterio- and veno-dilation, and preservation of renal function.  The authors concluded that BAT may be a promising therapy for HFpEF and introduced the HOPE4HF trial, a randomized outcomes trial designed to evaluate the clinical safety and effectiveness of BAT in the HFpEF population.

The Institute for Clinical Systems Improvement's clinical practice guideline on "Heart failure in adults" (ICSI, 2011) did not mention the use of BAT.

An European Heart Rhythm Association’s report on “New devices in heart failure” (Kuck et al, 2014) stated that several new devices for the treatment of HF patients have been introduced and are increasingly used in clinical practice or are under clinical evaluation in either observational and/or randomized clinical trials.  These devices include cardiac contractility modulation, spinal cord stimulation, carotid sinus nerve stimulation, cervical vagal stimulation, intra-cardiac atrio-ventricular nodal vagal stimulation, and implantable hemodynamic monitoring devices.

CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
ICD-10 codes will become effective as of October 1, 2015:
CPT codes not covered for indications listed in the CPB:
0266T	Implantation or replacement of carotid sinus baroreflex activation device; total system (includes generator placement, unilateral or bilateral lead placement, intra-operative interrogation, programming and repositioning, when performed)
0267T	Implantation or replacement of carotid sinus baroreflex activation device; lead only (includes intra-operative interrogation, programming and repositioning, when performed)
0268T	Implantation or replacement of carotid sinus baroreflex activation device; pulse generator only (includes intra-operative interrogation, programming and repositioning, when performed)
0269T	Revision or removal of carotid sinus baroreflex activation device; total system (includes generator placement, unilateral or bilateral lead placement, intra-operative interrogation, programming and repositioning, when performed)
0270T	Revision or removal of carotid sinus baroreflex activation device; lead only (includes intra-operative interrogation, programming and repositioning, when performed)
0271T	Revision or removal of carotid sinus baroreflex activation device; pulse generator only (includes intra-operative interrogation, programming and repositioning, when performed)
0272T	Interrogation device evaluation (in person), carotid sinus baroreflex activation system, including telemetric iterative communications with the implantable device to monitor device diagnostics and programmed therapy values, with interpretation and report (eg, battery status, lead impedance, pulse amplitude, pulse width, therapy frequency, pathway mode, burst node, therapy start/stop times each day)
0273T	Interrogation device evaluation (in person), carotid sinus baroreflex activation system, including telemetric iterative communications with the implantable device to monitor device diagnostics and programmed therapy values, with interpretation and report (eg, battery status, lead impedance, pulse amplitude, pulse width, therapy frequency, pathway mode, burst node, therapy start/stop times each day) with programming
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
I10 - I15.9	Hypertensive diseases
I50.1 - I50.9	Heart failure

The above policy is based on the following references:

Drug-Resistant Hypertension:

1. Illig KA, Levy M, Sanchez L, et al. An implantable carotid sinus stimulator for drug-resistant hypertension: Surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg. 2006;44(6):1213-1218.
2. Tordoir JH, Scheffers I, Schmidli J, et al. An implantable carotid sinus baroreflex activating system: Surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension. Eur J Vasc Endovasc Surg. 2007;33(4):414-421.
3. Doumas M, Guo D, Papademetriou V. Carotid baroreceptor stimulation as a therapeutic target in hypertension and other cardiovascular conditions. Expert Opin Ther Targets. 2009;13(4):413-425.
4. Joshi N, Taylor J, Bisognano JD. Implantable device therapy for the treatment of resistant hypertension. J Cardiovasc Transl Res. 2009;2(2):150-153.
5. Lovett EG, Schafer J, Kaufman CL. Chronic baroreflex activation by the Rheos system: An overview of results from European and North American feasibility studies. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:4626-4630.
   Heusser K, Tank J, Engeli S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55(3):619-626.
6. Sanchez LA, Illig K, Levy M, et al. Implantable carotid sinus stimulator for the treatment of resistant hypertension: Local effects on carotid artery morphology. Ann Vasc Surg. 2010;24(2):178-184.
7. Scheffers IJ, Kroon AA, Schmidli J, et al. Novel baroreflex activation therapy in resistant hypertension: Results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56(15):1254-1258.
8. Grassi G, Quarti-Trevano F, Brambilla G, Seravalle G. Blood pressure control in resistant hypertension: New therapeutic options. Expert Rev Cardiovasc Ther. 2010;8(11):1579-1585.
9. Taylor JG, Bisognano JD. Baroreflex stimulation in antihypertensive treatment. Curr Hypertens Rep. 2010;12(3):176-181.
10. Kougias P, Weakley SM, Yao Q, et al. Arterial baroreceptors in the management of systemic hypertension. Med Sci Monit. 2010;16(1):RA1-RA8.
11. Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation: Mechanisms and potential for hypertension therapy. Hypertension. 2011;57(5):880-886.
12. Ng MM, Sica DA, Frishman WH. Rheos: An implantable carotid sinus stimulation device for the nonpharmacologic treatment of resistant hypertension. Cardiol Rev. 2011;19(2):52-75.
13. Bisognano JD, Bakris G, Nadim MK, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: Results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58(7):765-773.
14. Hoppe UC, Brandt MC, Wachter R, et al. Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: Results from the Barostim neo trial. J Am Soc Hypertens. 2012;6(4):270-276.
15. Jordan J, Heusser K, Brinkmann J, Tank J. Electrical carotid sinus stimulation in treatment resistant arterial hypertension. Auton Neurosci. 2012;172(1-2):31-36.
16. Jordan J, Mann JF, Luft FC. Research needs in the area of device-related treatments for hypertension. Kidney Int. 2013;84(2):250-255.
17. Zhang J, Zhou S, Xu G. Carotid baroreceptor stimulation: A potential solution for resistant hypertension. Interv Neurol. 2014;2(3):118-122.
18. Chobanyan-Jurgens K, Jordan J. Electrical carotid sinus stimulation: Chances and challenges in the management of treatment resistant arterial hypertension. Curr Hypertens Rep. 2015;17(9):587.
19. Victor RG. Carotid baroreflex activation therapy for resistant hypertension. Nat Rev Cardiol. 2015;12(8):451-463.

Other Indications:

1. Georgakopoulos D, Little WC, Abraham WT, et al. Chronic baroreflex activation: A potential therapeutic approach to heart failure with preserved ejection fraction. J Card Fail. 2011;17(2):167-178.
2. Institute for Clinical Systems Improvement (ICSI). Heart failure in adults. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI); August 2011.
3. Kuck KH, Bordachar P, Borggrefe M, et al. New devices in heart failure: An European Heart Rhythm Association report: Developed by the European Heart Rhythm Association; endorsed by the Heart Failure Association. Europace. 2014;16(1):109-128.