Summary Of Evidence

OSA is a common, chronic disorder characterized by recurrent narrowing and/or closure of the upper airway accompanied by intermittent oxyhemoglobin desaturation, arousal from sleep and sympathetic activation.^1,2 Sequelae include disturbed sleep, excessive sleepiness and impaired quality of life (QOL). Moderate-to-severe OSA, defined as an AHI score of 15 or more apnea/hypopnea events per hour, is an independent risk factor for insulin resistance, dyslipidemia, vascular disease, and death.^3-7 Treatment with CPAP improves disturbed sleep; however, the general effectiveness of CPAP therapy is dependent on patient acceptance of and adherence to the treatment.^8,9 There are no effective options for patients with moderate-to-severe OSA for whom CPAP is ineffective or intolerant.

HNS has demonstrated safety and efficacy

Stimulation of the hypoglossal nerve that innervates the genioglossus is now a new therapeutic option for moderate and severe cases of obstructive sleep apnea-hypopnea syndrome (OSAHS). Two types of stimulation are currently available: (a) stimulation synchronous with inspiration and (b) continuous stimulation. Delgado, et al. concluded that indication of each type of stimulation and long-term effects still need to be assessed, but the implantable nerve stimulation is a promising treatment for patients without a therapy solution so far.¹⁰ In a multi-center, prospective, cohort study, Gillespie, et al. (2017) evaluated patient-based outcomes of subjects in a large cohort study (the Stimulation Therapy for Apnea Reduction [STAR] trial) 48 months after implantation with an upper airway stimulation (UAS) system for moderate-to-severe OSA. Patients (n = 91) at 48 months from a cohort of 126 implanted participants were included in this analysis.¹¹ A total of 126 subjects received an implanted UAS system in a prospective phase III clinical trial. Patient-reported outcomes at 48 months, including Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and snoring level, were compared with pre-implantation baseline. A total of 91 subjects completed the 48-month visit. Daytime sleepiness as measured by ESS was significantly reduced (p = 0.01), and sleep-related QOL as measured by FOSQ significantly improved (p = 0.01) when compared with baseline. Soft to no snoring was reported by 85% of bed partners; 2 patients needed additional surgery without complication for lead malfunction. The authors concluded that UAS maintained a sustained benefit on patient-reported outcomes (ESS, FOSQ, snoring) at 48 months in select patients with moderate-to-severe OSA. The authors stated that the main drawback of this study was the increased number of patients lost to follow-up at 48 months compared with 36 months (25 versus 4). Factors that influence adherence to follow-up include individual patient characteristics, social support, medical staff characteristics, and research study design. The trend of older age for those who completed follow-up versus those lost at 48 months was consistent with other trials that have noted poorer follow-up in younger cohorts, perhaps due to increased demands of work-life balance among younger subjects. With regard to medical staff, loss of a principal investigator and study-site support accounted for 20% of follow-up loss at 48 months. This trial, like many other multi-year trials, experienced greater loss of follow-up after 3 years. They noted that ongoing follow-up is needed to determine the natural product life of the device components.

In a prospective, multi-center, single-arm study, Steffen, et al. (2018) reported objective and patient-reported outcome after 12 months of implantation. Consecutive patients who received the UAS system (Inspire^® Medical Systems, Inc., Minneapolis, MN) were enrolled in 3 German centers.¹² Key study exclusion criteria included BMI greater than 35 kg/m², AHI less than 15 or greater than 65, or complete concentric collapse at the soft palate during sedated endoscopy. Data collection at 6- and 12- month visit include home sleep test and patient-reported outcome measures. Among the total of 60 participants, the median AHI reduced from 28.6 to 9.5 from baseline to 12 months. Patient-reported outcome measured in ESS and FOSQ both improved significantly from baseline to 12 months. The average usage time was 39.1 ± 14.9 hours per week among all participants based on recordings by the implanted device; 1 patient requested a removal of the device for cosmetic and other personal reasons and was completed without sequelae. The authors concluded that the findings of this study supported that UAS is a safe and effective therapeutic option for patients with OSA in routine clinical practice. However, the level of evidence was limited (IV) as this was an uncontrolled study with relatively small study with short-term follow-up.

Hofauer, et al. (2017) conducted a prospective cohort study to compare changes in sleep architecture during the diagnostic PSG and the post-implantation PSG in UAS in patients with OSA.¹³ The study included 26 patients who received a UAS device (Inspire^® Medical Systems). Treatment outcome was evaluated 2 and 3 months after surgery. Data collection included demographics, BMI, AHI, oxygen saturation and desaturation index (ODI), ESS, arousal parameter, and sleep patterns. The mean age was 60.2 years, 25 patients were male, 1 patient was female. Mean BMI was 29.0 kg/m². The mean pre-implantation AHI of 33.9/h could be reduced to 9.1/h at 2 months post-implantation (p < 0.001). The amount of time spent in N1-sleep could be reduced from 23.2% at baseline to 16.0% at month 3 post-implantation. The amount of time spent in N2- and N3-sleep did not change during the observation period. A significant increase of the amount of rapid-eye-movement (REM) sleep at month 2 (15.7%) compared to baseline (9.5%; p = 0.010) could be observed. A reduction of the number of arousals and the arousal index could be observed. The authors concluded that significant changes in sleep architecture of patients with OSA and sufficient treatment with UAS could be observed. A reduction of the amount of time spent in N1-sleep could be caused by treatment with UAS and the rebound of REM sleep, observed for the first time in a study on UAS, is also a potential marker of the efficacy of UAS on sleep architecture.

Huntley, et al. (2017) conducted a retrospective study to compare UAS for the treatment of OSA at 2 academic centers between May 2014 and August 2016.¹⁴ The investigators recorded demographic data, ESS, and preoperative and postoperative polysomnographic information. They compared outcome data between institutions and subsequently combined the cohorts and compared baseline to posttreatment results. Cohort 1 consisted of 30 males and 18 females with mean BMI of 29.3 kg/m². The mean preoperative AHI, O2 nadir, and ESS were 35.88, 80.96, and 11.09, respectively. The mean postoperative AHI, O2 nadir, and ESS were 6.34, 88.04, and 5.77, respectively. Cohort 2 consisted of 30 males and 19 females with a mean BMI of 27.7 kg/m². The mean preoperative AHI, O2 nadir, and ESS were 35.29, 79.58, and 10.94, respectively. The mean postoperative AHI, O2 nadir, and ESS were 6.28, 84.35, and 6.60, respectively. The investigators found no difference in patients reaching a postoperative AHI less than 15, 10, and 5 when comparing the cohorts. After combining cohorts, they found a significant improvement in postoperative AHI, O2 nadir, and ESS compared to preoperative values. Huntley and colleagues concluded that UAS appears to provide a viable alternative to CPAP, producing improvement in both polysomnographic and QOL measures. The study established that results are reproducible at high-volume centers. 

The position statement from the American Academy of Otolaryngology (AAO) (2016) states that:

“The AAO considers upper airway stimulation (UAS) via the hypoglossal nerve for the treatment of adult obstructive sleep apnea syndrome to be an effective second-line treatment of moderate to severe obstructive sleep apnea in patients who are intolerant or unable to achieve benefit with positive pressure therapy (PAP). Not all adult patients are candidates for UAS therapy and appropriate polysomnographic, age, BMI and objective upper airway evaluation measures are required for proper patient selection.”

FDA eligibility criteria for HNS implantation

The Inspire^® UAS (Inspire^® Medical Systems, Inc.) is an FDA-approved implanted upper airway stimulator that includes an implantable pulse generator and leads system, and external programmer indicated for second-line treatment of adult patients with moderate-to-severe OSA. The system delivers mild stimulation to the hypoglossal nerve which controls the movement of the tongue and other key airway muscles. By stimulating these muscles, the airway remains open during sleep. The FDA eligibility criteria for the UAS implantation include age 22 years of age and older, moderate or severe OSA (defined as AHI 20 to 65 events/hour), predominantly obstructive events (defined as central and mixed apneas less than 25% of the total AHI), CPAP failure (defined as AHI >20 on CPAP) or intolerance (defined as use <4 hours per night, 5 nights per week; or unwillingness to use), no complete concentric velopharyngeal collapse on screening sleep endoscopy, and no other anatomical findings that would compromise performance of the device (e.g., tonsil size 3 or 4). It is not recommended for patients with BMI >32 kg/m² (FDA, 2014; Inspire^® Medical Systems, 2014; UpToDate^®, 2017). Patients who are pregnant or plan to become pregnant, are unable or do not have the necessary assistance to operate the sleep remote, will require MRI (excluding Inspire^® 3028 system which has MRI labeling), or any condition or procedure that has compromised neurological control of the upper airway, are considered contraindications for hypoglossal nerve UAS implantation (FDA, 2014). Per Inspire^® Medical Systems, having a cardiac pacemaker is not a contraindication for the Inspire^® device. In March 2017, the FDA approved to expand the AHI range from 20-65, to 15-65 events/hour (FDA, 2017).

In June 2017, Inspire^® Medical Systems, Inc. announced the FDA approval for the next-generation device, Inspire 3028 implantable pulse generator, which includes magnetic resonance (MR) conditional labeling to allow patients to undergo MRI safely. The Inspire 3028 device is 40% smaller and 18% thinner than the current Inspire neurostimulator which received FDA approval in April 2014. Patients can undergo MRI on the head and extremities if certain conditions and precautions are met (Inspire^® Medical Systems, 2017). Additionally, the AHI range was extended from 20-65 events/hour to 15-65 events/hour.

HNS long-term safety and efficacy demonstrated

Woodson, et al. (2018) evaluated 5-year outcomes of UAS from a multicenter prospective cohort study of 126 patients with OSA who were treated with UAS via a unilateral hypoglossal nerve implant.¹⁵ Those having CPAP failure with moderate-to-severe OSA, BMI <32 kg/m², and no unfavorable collapse on DISE were enrolled in the phase 3 trial. Outcomes evaluated included AHI, ODI, and adverse events, as well as measures of sleepiness, QOL, and snoring. Improvement in ESS and QOL was observed, with normalization of scores increasing from 33% to 78% and 15% to 67%, respectively. AHI response rate (AHI <20 events/hour and >50% reduction) was 75% (n = 71). "When a last observation carried forward analysis was applied, the responder rate was 63% at 5 years. Serious device-related events all related to lead/device adjustments were reported in 6% of patients." The authors concluded that improvements in sleepiness, QOL, and respiratory outcomes were observed with 5 years of UAS. Serious adverse events were uncommon. The authors reported that "UAS is a non-anatomic surgical treatment with long-term benefit for individuals with moderate to severe OSA who have failed nasal CPAP."

Drug Induced Sleep Endoscopy (DISE)

There is evidence of moderate limitations in inter-rater reliability for determining if complete concentric collapse (CCC) is present during DISE.¹⁶ To reduce variation in patient selection and optimize outcomes, a second-opinion to confirm DISE reporting is recommended.

Shared Decision-Making

SDM incorporates the patient’s values and preferences into medical decisions and puts the patient at the center of care. Studies suggest that patient-provider communication about nontechnical aspects of care improves patient satisfaction and positively affects health outcomes.^17-19

Analysis of Evidence

Level of evidence – Good (I-IIb, with risks of bias)

Strength of recommendation – Good 

Based on the best available evidence, selected patients who have symptoms and signs of moderate-to-severe OSA and demonstrate either CPAP failure or intolerance are appropriate candidates for HNS. A critical mass of level I-IIb evidence, including data with FDA-approved devices at multiple sites with short-, mid-, and long-term follow up and specialty society endorsement is compelling enough to consider HNS as a reasonable option for surgical treatment of OSA in select patients. The evidence is sufficient to determine that the technology results in meaningful improvements in the net health outcome.

Hypoglossal nerve stimulation (HNS) is reasonable and necessary for the treatment of moderate to severe obstructive sleep apnea (OSA) when all of the following criteria are met:

1. Beneficiary is 22 years of age or older; and
2. Body mass index (BMI) is less than 35 kg/m²; and
3. A polysomnography (PSG) demonstrating an apnea-hypopnea index (AHI) of 15 to 65 events per hour within 24 months of initial consultation for HNS implant; and
4. Beneficiary has predominantly obstructive events (defined as central and mixed apneas less than 25% of the total AHI); and
5. Shared Decision-Making (SDM) between the Beneficiary, Sleep physician, AND qualified otolaryngologist (if they are not the same) who determines that the Beneficiary demonstrates continuous positive airway pressure (CPAP) failure (defined as AHI greater than 15 despite CPAP usage) or CPAP intolerance (defined as CPAP machine-derived compliance reporting with usage less than 4 hours a night for at least 70% of the nights in 1 month, or the CPAP has been returned) despite CPAP interface and/or setting optimizations.
6. Confirmed absence of complete concentric collapse at the soft palate level by a drug-induced sleep endoscopy (DISE) procedure; and
7. Absence of anatomical findings that would compromise performance of device (e.g., tonsil size 3 or 4 per standardized tonsillar hypertrophy grading scale).
8. Use of HNS devices with United States (U.S.) Food and Drug Administration (FDA)-approval for implantation to treat OSA (e.g., Inspire^® II Upper Airway Stimulator).

HNS is not reasonable or necessary when any 1 of the following contraindications are present:

• Beneficiaries with central and mixed apneas that make up more than one-quarter of the total AHI
• BMI 35 kg/m² or greater
• Neuromuscular disease
• Hypoglossal-nerve palsy
• Severe restrictive or obstructive pulmonary disease
• Moderate-to-severe pulmonary arterial hypertension
• Severe valvular heart disease
• New York Heart Association class III or IV heart failure
• Recent myocardial infarction or severe cardiac arrhythmias (within the past 6 months)
• Persistent uncontrolled hypertension despite medication use
• Acute psychiatric disease
• Coexisting non-respiratory sleep disorders that would confound functional sleep assessment
• Beneficiaries who are, or who plan to become pregnant
• Beneficiaries who are unable or do not have the necessary assistance to operate the device's external programmer
• Beneficiaries with any condition or procedure that has compromised neurological control of the upper airway
• HNS implant devices that are not compatible with magnetic resonance imaging (MRI) in Beneficiaries who require MRI

NOTE: Beneficiaries with certain HNS devices can undergo MRI of the head and extremities if certain conditions and precautions are met. Please refer to the Manufacturer Guidelines for the relevant model for more information.

Credentialing and Accreditation Standards

Provider Qualifications for HNS Implantation and Device Management

Optimal outcomes of HNS implantation procedures depend on the knowledge, skill and experience of the provider(s). Consequently, the qualified provider performing the procedure must be capable of demonstrating documented training and experience relevant to HNS implantation.

HNS-implantation services will only be considered reasonable and necessary if provided in facilities with standards of medical practice and personnel appropriate for the patient’s medical needs, risk of adverse events, and when performed by qualified providers with all of the following:

• All HNS implantation procedures must be performed by a licensed qualified physician

• A licensed qualified physician (MD or DO) for HNS services is defined as:

• Having trained and acquired expertise within the framework of an accredited residency or fellowship program in the applicable specialty/subspecialty (e.g., Board-eligible (BE) or Board-certified (BC) otolaryngologist) or must reflect equivalent education, training and expertise endorsed by a relevant specialty/subspecialty society, and

• Prior to implanting the system, surgeons will have received education and proctoring by an FDA-approved device manufacturer or equivalent proctoring body on device implant techniques, including cadaver training. Documentation must be available for contractor review to provide confirmation of proficiency in the performance and management of HNS implantation and the corresponding relevant devices.

• The provider performing DISE shall be certified by the FDA-approved manufacturer’s second opinion service of validation via video clip submissions of at least 80% agreement in at least 15 consecutive studies. Documentation of this proficiency must be available to submit for contractor review.

Excluding routine post-op care by the implanting surgeon (e.g., initial empiric programming), initial consultation and post-implant evaluation and management of Beneficiaries appropriate for HSN devices must be performed by BE or BC Sleep physicians with qualifications as outlined in LCD L36593 [Polysomnography] and Article A55958 [Accreditation and Credentialing Requirements for Polysomnography LCD L36593]. Additionally, sleep studies shall be performed by an accredited sleep facility as stated in LCD L36593. Please refer to the Article A55958 regarding Independent Diagnostic Testing Facility (IDTF) for additional information. BC/BE Sleep physicians must complete HNS device education and training (including hands-on operation of the external programmer) by an FDA-approved device manufacturer or equivalent proctoring body.