Hypoglossal nerve stimulation versus positive airway pressure therapy for obstructive sleep apnea.

PURPOSE: Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea-hypopnea index (AHI), and (3) effectiveness. METHODS: Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated. RESULTS: Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP. CONCLUSION: Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03756805.

Similar effect of hypoglossal nerve stimulation for obstructive sleep apnea in 5 disease severity categories.

STUDY OBJECTIVES: Data on adherence and outcome of upper airway stimulation (UAS) for patients with obstructive sleep apnea (OSA) are collected in an international registry (ADHERE). Previous publications report significant improvement in self-reported and objective OSA outcomes, durable effectiveness, and high adherence. Debate remains whether the effectiveness of UAS is influenced by preoperative OSA severity; therefore, we aimed to evaluate this using data from the ADHERE Registry. METHODS: ADHERE is a postmarket, ongoing, international multicenter registry. Adult patients were included if they had undergone UAS implantation and had at least 1 follow-up visit recorded in the database on June 8, 2021. We divided the patients into 5 subgroups, based on OSA severity at baseline (AHI in events/h): subgroup 1 (0-15), 2 (15-30), 3 (≥ 30-50), 4 (> 50-65), and 5 (> 65). We compared results regarding objective and self-reported treatment outcomes. RESULTS: A total of 1,963 patients were included. Twelve months after implantation, there was a significant (P < .0001) improvement in objective sleep parameters in all subgroups with an AHI above 15 events/h. Patients in subgroup 1 had the lowest AHI at the final visit and the AHI reduction in patients in subgroup 5 was the largest (P < .0001). No significant difference was found between the subgroups in overall treatment success (66.6%) and improvement in self-reported outcomes. CONCLUSIONS: Our results suggest that UAS is an effective treatment for patients with an AHI ≥ 15 events/h, independent of preoperative OSA severity. Self-reported outcomes and treatment success did not differ significantly between the 5 subgroups. These results clearly support that the indication of UAS could be broadened for patients with an AHI above 65 events/h, which, to date, is not common practice. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Adherence and Outcome of Upper Airway Stimulation (UAS) for OSA International Registry (ADHERE Registry); Identifier: NCT02907398; URL: https://www.clinicaltrials.gov/ct2/show/NCT02907398. CITATION: Bosschieter PFN, de Vries N, Mehra R, et al. Similar effect of hypoglossal nerve stimulation for obstructive sleep apnea in 5 disease severity categories. J Clin Sleep Med. 2022;18(6):1657-1665.

Endotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

Rationale: Approximately one-third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy.Objectives: Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy.Methods: Baseline polysomnography data of the STAR (Stimulation Therapy for Apnea Reduction) trial were included. Raw baseline polysomnographic data from 91/126 patients were available for analysis. Traits-loop gain, arousal threshold, collapsibility, and muscle compensation-were calculated from the baseline polysomnography data according to Sands and colleagues (AJRCCM 2018, SLEEP 2018). Logistic regression assessed apnea-hypopnea index (AHI)-adjusted associations between HGNS response (>50% reduction in AHI to <10/h at 1 yr) and OSA traits.Measurements and Main Results: Overall, HGNS treatment reduced AHI from 30.7 (24.9-39.9) to 8.5 (4.0-19.5) events/h (P < 0.0001; median [quartiles 1-3]); N = 53/91 were responders. In adjusted analysis, a favorable response to therapy was independently associated with higher arousal threshold (odds ratio [95% confidence interval]: 6.76 [2.44-23.3], P = 0.001), greater compensation (odds ratio: 4.22 [1.70-12.55] per SD, P = 0.004), and lower loop gain (in milder collapsibility, per significant interaction, P = 0.003). The higher arousal threshold was evident in responders before adjusted analysis. Predicted responders had an approximately fourfold lower treatment AHI versus predicted nonresponders (4.9 [2.7-8.5] vs. 20.7 [10.9-29.7], P < 0.0001; median [quartiles 1-3]); differences remained significant after cross-validation.Conclusions: Favorable responses to HGNS therapy are associated with the pathophysiological traits causing OSA, particularly a higher arousal threshold. Along with established criteria, individuals with favorable traits could potentially be prioritized for precision HGNS therapy.This analysis was a secondary analysis of the STAR trial registered with clinicaltrials.gov (NCT01161420).

Sex Differences in the Response to Different Tinnitus Treatment.

INTRODUCTION: Tinnitus is a complex symptom requiring a thorough multidisciplinary assessment to construct an individual's tinnitus profile. The Antwerp University Hospital hosts a tertiary tinnitus clinic providing intensive, multidisciplinary tinnitus care in the form of combinational psychological treatment with either Tinnitus Retraining Therapy (TRT)/Cognitive Behavioral Therapy (CBT) or TRT/eye movement desensitization and reprocessing therapy (EMDR), high-definition transcranial direct current stimulation (HD-tDCS), and physical therapy treatment (in cases of somatic influence of the neck or the temporomandibular area). Several factors may contribute to therapy effect of which the role of gender has recently gained more interest. As such, the current manuscript explores gender differences in the outcome of different tinnitus treatments. METHODS: Data on treatment outcome of four distinct tinnitus treatments (1. HD-tDCS; 2. orofacial physical therapy; 3. combination TRT + CBT; and 4. combination TRT + EMDR) were pooled and compared. Treatment outcome was assessed via the Tinnitus Functional Index (TFI). Participants completed the TFI at baseline, immediately after treatment and after 9 weeks (±3 weeks) follow-up. To explore the effect of gender on different treatment outcomes, a linear mixed model was designed including Time point, Gender, and Therapy Group as fixed factors as well as all interactions between these factors. RESULTS: TFI scores improved significantly over time regardless of therapy group (p < 0.0001). A mean TFI decrease of at least 13 points was obtained by all participants except by those in the HD-tDCS. Significant interactions between Gender and Time point were identified in all groups except for the TRT +EMDR group. Female subjects improved more extensively than males in the HD-tDCS (p = 0.0009) and orofacial therapy group (p = 0.0299). Contrarily, in the TRT +CBT group, male participants showed a significant improvement whereas the mean TFI scores of female subjects remained on baseline levels (p = 0.0138). CONCLUSION: Our data suggest that male and female tinnitus patients seem to react differently to different therapy options. We strongly encourage further prospective studies to discern the relevance of gender in therapy outcome.

Development of a standardized evaluation of endobuccal adverse events induced by repeated tongue protrusion with both a dedicated questionnaire and an endobuccal examination.

INTRODUCTION: A new approach to treat obstructive sleep apnea (OSA) is upper airway stimulation therapy (UAS). Electrical pulses applied to the hypoglossal nerve induce tongue protrusion, increase airway patency and decrease the frequency of apneic and hypopneic events. Thus, the main objective of this study was to design a standardized evaluation of endobuccal adverse events induced by repeated tongue protrusion with both a dedicated questionnaire and an endobuccal examination. METHOD: This study has designed the Tongue Adverse Event and Satisfaction Questionnaire (TAESQ) and an endobuccal examinations divided into an endobuccal lesion examination (ELE) and an endobuccal risk factor examination (ERFE). Evaluations were conducted at month 6 post-implantation. RESULTS: The study population after implantation of UAS device consisted of ten Caucasian males with a mean age of 51.9 ± 11.8 years, and a mean BMI of 28.6 ± 3.3. The AHI of the ten participants ranged from 46.7 ± 12.2/h at baseline to 14.5 ± 8.9/h with the Inspire therapy at the 6-month follow-up. The TAESQ revealed pain (30%), followed by less tongue sensitivity (20%) and tongue weakness (10%). The ELE did not reveal any lesions. The ERFE revealed that some participants had tissue and dental risk factors but not associated to more adverse events. CONCLUSION: The TAESQ, ELE and ERFE have been designed and studied on a small number of participants. These evaluations could systematically be included in the care pathway of patients treated by UAS to better investigate tongue discomfort and tongue lesion for patients treated with this technology.

Successful upper airway stimulation therapy in an adult Down syndrome patient with severe obstructive sleep apnea.

PURPOSE: The aim of this study was to report on the successful application of upper airway stimulation (UAS) therapy in an adult Down syndrome (DS) patient with severe obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) intolerance. METHODS: Baseline polysomnography (PSG) in a 23-year-old male OSA patient (body mass index (BMI) 24.4 kg/m2) revealed an apnea/hypopnea index (AHI) of 61.5 events/h and oxygen desaturation index (ODI) of 39.7 events/h. Based on the clinical examination, PSG and drug-induced sleep endoscopy, the patient fulfilled the formal inclusion criteria for UAS therapy: AHI between 15 and 65 events/h, BMI < 32 kg/m2, and no complete concentric collapse at the level of the velopharynx. RESULTS: Implantation of the hypoglossal nerve stimulator in the adult patient with DS resulted in a substantial subjective as well as objective improvement of OSA (63 to 81% decrease in AHI and 77% decrease in ODI), translating into an overall satisfactory outcome. CONCLUSION: Research on the long-term effectiveness of UAS therapy in a larger group of patients with DS is needed. However, based on the available literature and our presented case, respiration-synchronized electrostimulation of the hypoglossal nerve using UAS therapy may have a potential value in well-selected OSA patients with DS who are non-compliant to CPAP therapy.

Upper Airway Stimulation for Obstructive Sleep Apnea: 5-Year Outcomes.

Objective To present 5-year outcomes from a prospective cohort of patients with obstructive sleep apnea (OSA) who were treated with upper airway stimulation (UAS) via a unilateral hypoglossal nerve implant. Study Design A multicenter prospective cohort study. Setting Industry-supported multicenter academic and clinical trial. Methods From a cohort of 126 patients, 97 completed protocol, and 71 consented to a voluntary polysomnogram. Those having continuous positive airway pressure failure with moderate to severe OSA, body mass index <32 kg/m2, and no unfavorable collapse on drug-induced sleep endoscopy were enrolled in a phase 3 trial. Prospective outcomes included apnea-hypopnea index (AHI), oxygen desaturation index, and adverse events, as well as measures of sleepiness, quality of life, and snoring. Results Patients who did and did not complete the protocol differed in baseline AHI, oxygen desaturation index, and Functional Outcomes of Sleep Questionnaire scores but not in any other demographics or treatment response measures. Improvement in sleepiness (Epworth Sleepiness Scale) and quality of life was observed, with normalization of scores increasing from 33% to 78% and 15% to 67%, respectively. AHI response rate (AHI <20 events per 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. Conclusions Improvements in sleepiness, quality of life, and respiratory outcomes are observed with 5 years of UAS. Serious adverse events are uncommon. UAS is a nonanatomic surgical treatment with long-term benefit for individuals with moderate to severe OSA who have failed nasal continuous positive airway pressure.

Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea.

Study Objectives: Upper airway stimulation has been shown to be an effective treatment for some patients with obstructive sleep apnea. However, the mechanism by which hypoglossal nerve stimulation increases upper airway caliber is not clear. Therefore, the objective of this study was to identify the mechanism of action of upper airway stimulation. We hypothesized that, with upper airway stimulation, responders would show greater airway opening in the retroglossal (base of the tongue) region, greater hyoid movement toward the mandible, and greater anterior motion in the posterior, inferior region of the tongue compared with nonresponders. Methods: Seven participants with obstructive sleep apnea who had been successfully treated with upper airway stimulation (responders) and six participants who were not successfully treated (nonresponders) underwent computed tomography imaging during wakefulness with and without hypoglossal nerve stimulation. Responders reduced their apnea-hypopnea index (AHI) by 22.63 ± 6.54 events per hour, whereas nonresponders had no change in their AHI (0.17 ± 14.04 events per hour). We examined differences in upper airway caliber, the volume of the upper airway soft tissue structures, craniofacial relationships, and centroid tongue and soft palate movement between responders and nonresponders with and without hypoglossal nerve stimulation. Results: Our data indicate that compared with nonresponders, responders had a smaller baseline soft palate volume and, with stimulation, had (1) a greater increase in retroglossal airway size; (2) increased shortening of the mandible-hyoid distance; and (3) greater anterior displacement of the tongue. Conclusions: These results suggest that smaller soft palate volumes at baseline and greater tongue movement anteriorly with stimulation improve the response to upper airway stimulation.

Upper Airway Stimulation for Obstructive Sleep Apnea: Patient-Reported Outcomes after 48 Months of Follow-up.

Objective To assess patient-based outcomes of participants in a large cohort study-the STAR trial (Stimulation Therapy for Apnea Reduction)-48 months after implantation with an upper airway stimulation system for moderate to severe obstructive sleep apnea. Study Design A multicenter prospective cohort study. Setting Industry-supported multicenter academic and clinical setting. Subjects Participants (n = 91) at 48 months from a cohort of 126 implanted participants. Methods A total of 126 participants received an implanted upper airway stimulation system in a prospective phase III trial. Patient-reported outcomes at 48 months, including Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and snoring level, were compared with preimplantation baseline. Results A total of 91 subjects completed the 48-month visit. Daytime sleepiness as measured by ESS was significantly reduced ( P = .01), and sleep-related quality of life as measured by FOSQ significantly improved ( P = .01) when compared with baseline. Soft to no snoring was reported by 85% of bed partners. Two patients required additional surgery without complication for lead malfunction. Conclusion Upper airway stimulation maintained a sustained benefit on patient-reported outcomes (ESS, FOSQ, snoring) at 48 months in select patients with moderate to severe obstructive sleep apnea.

Upper Airway Stimulation for Obstructive Sleep Apnea: Self-Reported Outcomes at 24 Months.

OBJECTIVES: To evaluate the long-term (24-mo) effect of cranial nerve upper airway stimulation (UAS) therapy on patient-centered obstructive sleep apnea (OSA) outcome measures. METHODS: Prospective, multicenter, cohort study of 126 patients with moderate to severe OSA who had difficulty adhering to positive pressure therapy and received the surgically implanted UAS system. Outcomes were measured at baseline and postoperatively at 12 mo and 24 mo, and included self- and bedpartner-report of snoring intensity, Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ). Additional analysis included FOSQ subscales, FOSQ-10, and treatment effect size. RESULTS: Significant improvement in mean FOSQ score was observed from baseline (14.3) to 12 mo (17.3), and the effect was maintained at 24 mo (17.2). Similar improvements and maintenance of effect were seen with all FOSQ subscales and FOSQ-10. Subjective daytime sleepiness, as measured by mean ESS, improved significantly from baseline (11.6) to 12 mo (7.0) and 24 mo (7.1). Self-reported snoring severity showed increased percentage of "no" or "soft" snoring from 22% at baseline to 88% at 12 mo and 91% at 24 mo. UAS demonstrated large effect size (> 0.8) at 12 and 24 mo for overall ESS and FOSQ measures, and the effect size compared favorably to previously published effect size with other sleep apnea treatments. CONCLUSIONS: In a selected group of patients with moderate to severe OSA and body mass index ≤ 32 kg/m2, hypoglossal cranial nerve stimulation therapy can provide significant improvement in important sleep related quality-of-life outcome measures and the effect is maintained across a 2-y follow-up period.

Three-Year Outcomes of Cranial Nerve Stimulation for Obstructive Sleep Apnea: The STAR Trial.

OBJECTIVE: To describe the 36-month clinical and polysomnography (PSG) outcomes in an obstructive sleep apnea (OSA) cohort treated with hypoglossal cranial nerve upper airway stimulation (UAS). STUDY DESIGN: A multicenter prospective cohort study. SETTING: Industry-supported multicenter academic and clinical setting. SUBJECTS: Participants (n = 116) at 36 months from a cohort of 126 implanted participants. METHODS: Participants were enrolled in a prospective phase III trial evaluating the efficacy of UAS for moderated to severe OSA. Prospective outcomes included apnea-hypopnea index, oxygen desaturation index, other PSG measures, self-reported measures of sleepiness, sleep-related quality of life, and snoring. RESULTS: Of 126 enrolled participants, 116 (92%) completed 36-month follow-up evaluation per protocol; 98 participants additionally agreed to a voluntary 36-month PSG. Self-report daily device usage was 81%. In the PSG group, 74% met the a priori definition of success with the primary outcomes of apnea-hypopnea index, reduced from the median value of 28.2 events per hour at baseline to 8.7 and 6.2 at 12 and 36 months, respectively. Similarly, self-reported outcomes improved from baseline to 12 months and were maintained at 36 months. Soft or no snoring reported by bed partner increased from 17% at baseline to 80% at 36 months. Serious device-related adverse events were rare, with 1 elective device explantation from 12 to 36 months. CONCLUSION: Long-term 3-year improvements in objective respiratory and subjective quality-of-life outcome measures are maintained. Adverse events are uncommon. UAS is a successful and appropriate long-term treatment for individuals with moderate to severe OSA.

Implanted upper airway stimulation device for obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success. STUDY DESIGN: Two consecutive open prospective studies. METHODS: UAS systems were implanted in patients with moderate to severe OSA who failed or were intolerant of continuous positive airway pressure (CPAP). The study was conducted in 2 parts. In part 1, patients were enrolled with broad selection criteria. Apnea hypopnea index (AHI) was collected using laboratory-based polysomnography at preimplant and postimplant visits. Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also collected. In part 2, patients were enrolled using selection criteria derived from the experience in part 1. RESULTS: In part 1, 20 of 22 enrolled patients (two exited the study) were examined for factors predictive of therapy response. Responders had both a body mass index ≤32 and AHI ≤50 (P < .05) and did not have complete concentric palatal collapse. Part 2 patients (n = 8) were selected using responder criteria and showed an improvement on AHI from baseline, from 38.9 ± 9.8 to 10.0 ± 11.0 (P < .01) at 6 months postimplant. Both ESS and FOSQ improved significantly in part 1 and 2 subjects. CONCLUSIONS: The current study has demonstrated that therapy with upper airway stimulation is safe and efficacious in a select group of patients with moderate to severe OSA who cannot or will not use CPAP as primary treatment.

Cardiovascular implications in the treatment of obstructive sleep apnea.

Epidemiological studies provide strong evidence that obstructive sleep apnea (OSA) is associated with cardiovascular complications such as systemic hypertension, congestive heart failure, and atrial fibrillation. Successful OSA treatment with continuous positive airway pressure (CPAP) has resulted in coincident reductions in systemic hypertension, improvements in left ventricular systolic function, and reductions in sympathetic nervous activity. These data suggest that successful treatment of OSA may reduce cardiovascular morbidity in such patients. Although CPAP is the more successful treatment for OSA when used properly and consistently, its clinical success is often limited by poor patient and partner acceptance, which leads to suboptimal compliance. Oral appliances or upper airway surgeries are considered a second line of treatment for patients with mild to moderate OSA who do not comply with or refuse long-term CPAP treatment. Oral devices such as mandibular repositioning appliances were recently shown to improve arterial hypertension in OSA patients. Electrical stimulation of the hypoglossal nerve is a new investigational therapy for patients with moderate to severe OSA. This new treatment option, if proven effective, may provide cardiovascular benefits secondary to treating OSA.