Hypoglossal Nerve Stimulation Therapy Research Articles

Baseline Characteristics Associated with Hypoglossal Nerve Stimulation Treatment Outcomes in Patients with Obstructive Sleep Apnea: A Systematic Review

Hypoglossal nerve stimulation (HGNS) has emerged as an effective treatment for obstructive sleep apnea (OSA). Identifying baseline characteristics that prospectively could predict treatment outcomes even better is crucial for optimizing patient selection and improving therapeutic success in the future. A systematic review was conducted following PRISMA guidelines. Literature searches in Medline, Web of Science, and Cochrane databases identified studies assessing baseline characteristics associated with HGNS treatment outcomes. Inclusion criteria focused on studies with adult patients diagnosed with OSA, treated with HGNS, and assessed using full-night efficacy sleep studies. Risk of bias was evaluated using the NICE tool. Twenty-six studies met the inclusion criteria. Commonly reported baseline characteristics with predictive potential included BMI, site of collapse, and various pathophysiological endotypes. Most studies used the original Sher criteria to define treatment response, though variations were noted. Results suggested that lower BMI, absence of complete concentric collapse at the palatal level, and specific pathophysiological traits were associated with better HGNS outcomes. This review identified several baseline characteristics associated with HGNS outcomes, which may guide future patient selection. Importantly, patients were already preselected for HGNS. Standardizing response criteria is recommended to enhance the evaluation and effectiveness of HGNS therapy in OSA patients.

Comparison of Home Sleep Devices and Sleep Study Testing in Hypoglossal Nerve Stimulation Patients.

Hypoglossal nerve stimulation (HGNS) is an implantable therapy for obstructive sleep apnea (OSA). Therapy efficacy is currently confirmed by a formal sleep study after empiric adjustment by the patient at home based on their subjective experience with the device. Home-based longitudinal apnea hypopnea index (AHI) measurements have the potential to refine HGNS therapeutic amplitude selection with objective data. Our objective was to compare AHI derived from routine sleep studies and two different home sleep devices in new HGNS recipients. Prospectively enrolled patients receiving HGNS therapy were provided a Sleep Tracking Mat (Withings, Issy-les-Moulineaux, France) and NightOwl peripheral arterial tonometry (PAT) sensor (Ectosense, Leuven, Belgium) for longitudinal, home AHI monitoring from 1 to 6 months post-implant. Therapy efficacy was assessed at 3 and 6 months post-implant using in-lab polysomnography (PSG) or home sleep apnea test (HSAT). The sleep mat and PAT sensor AHI were compared against PSG and HSAT for accuracy of OSA severity identification. Sixty patients were enrolled across 5 centers and followed for 6 months. The sleep mat had sensitivity and specificity for identifying AHI <15 of 61% and 82% and AHI <30 of 77% and 100%. The PAT device had sensitivity and specificity for identifying AHI <15 of 57% and 77% and AHI <30 of 81% and 80%. The sleep mat and PAT sensor demonstrated high sensitivity and specificity for detection of mild and moderate OSA in patients with HGNS therapy and may enable longitudinal objective monitoring of HGNS efficacy in the home setting. 3 Laryngoscope, 2024.

Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea-A Systematic Review of Clinical Trials and Real-World Data.

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data.

The impact of neck circumference on hypoglossal nerve stimulator therapy outcomes.

Hypoglossal nerve stimulation (HGNS) therapy has historically had strict eligibility requirements including a body mass index (BMI) < 32 kg/m2. However, recent Food and Drug Administration approval expanded indications to a BMI < 40 kg/m2. There is a wide variability in body fat distribution. This study sought to determine if neck circumference is a better surrogate predictive variable for HGNS outcomes than BMI. A retrospective chart review was conducted at a tertiary care center on adults who underwent HGNS implantation by a single surgeon from March 2017 to October 2021. Baseline demographic data including neck circumference, diagnostic sleep studies and post-implantation HGNS titration studies were collected. Linear regression and Spearman's Correlation Coefficient (SCC) analysis were utilized to compare neck circumference (NC), percentage of predicted neck circumference (PPNC) and BMI with the apnea-hypopnea index at effective voltage (AHI-v). This study included 43 patients who were middle aged (61.1 years), predominantly male (76.7%), with severe obstructive sleep apnea (median AHI 35) and mean neck circumference of 15.3 inches. Utilizing the NC and PPNC, positive correlations with AHI-v were observed (p = 0.0033, SCC = .438, and p = 0.0029, SCC = .444). While controlling for BMI, a 1-inch increase in neck circumference was associated with a 35% increase in AHI-v (p = 0.0411). A larger neck circumference was independently associated with worse HGNS outcomes. Further research is needed to support and confirm these findings, particularly across sexes.

Hypoglossal Nerve Stimulation Therapy in a Belgian Cohort of Obstructive Sleep Apnea Patients.

Hypoglossal nerve stimulation (HGNS) has emerged as a widespread and innovative treatment option for selected moderate-to-severe obstructive sleep apnea (OSA) patients who cannot be treated effectively with traditional treatment modalities. In this observational cohort study, the objective and subjective outcomes of Belgian OSA patients treated with HGNS therapy were analyzed at 6 and 12 months post-implantation. Thirty-nine patients implanted with a respiration-synchronized HGNS device at the Antwerp University Hospital w ere included in this study. Patients underwent baseline in-laboratory polysomnography and a follow-up sleep study 6 and 12 months post-implantation. Questionnaires on patient experience and daytime sleepiness were filled out and data on objective therapy usage were collected. All 39 patients completed the 6-month follow-up and 21 patients (54%) completed the 12-month follow-up. Median AHI decreased from 33.8 [26.1;45.0] to 10.2 [4.8;16.4] at the 6-month follow-up, and to 9.6 [4.1;16.4] at the 12-month follow-up (p < 0.001). The surgical success rate, according to the Sher20 criteria, was 80% and 76% at the 6- and 12-month follow-ups, respectively. Median ESS improved from 12.0 [7.0;18.0] at baseline to 6.0 [2.5;11.0] at 6 months (p < 0.001) and to 6.5 [2.8;11.5] at 12 months (p = 0.012). Objective therapy usage was 7.4 [6.6;8.0] and 7.0 [5.9:8.2] h/night at the 6- and 12-month follow-ups, respectively. A high overall clinical effectiveness of HGNS therapy, as shown by a mean disease alleviation of 58%, was demonstrated at 12 months post-implantation. Overall, HGNS therapy using respiration-synchronized neurostimulation of the XII cranial nerve resulted in a significant improvement in both objective and subjective OSA outcomes, with a high level of patient satisfaction and high treatment adherence.

Are There Hidden Adverse Events in Hypoglossal Nerve Stimulation: Comparing Social Media and a Federal Database.

Hypoglossal nerve stimulation (HNS) can be an effective treatment for moderate to severe obstructive sleep apnea (OSA) in positive airway pressure (PAP) intolerant patients. To better understand patient experiences with HNS therapy, we explored reported events from HNS-related Facebook groups and the Manufacturer and User Facility Device Experience (MAUDE) database. A retrospective analysis of HNS-related Facebook posts from three groups pertaining to HNS therapy, from October 1, 2022 to October 1, 2023, was performed. Posts were analyzed for patient-reported adverse events. Concurrently, the MAUDE database was reviewed for HNS-related events during the same timeframe. From 737 Facebook posts, 132 (17.55%) adverse events were identified. Adverse events included pain (34.85%), stimulation discomfort (14.39%), lip weakness (6.82%) and issues related to lead tethering or tight leads around the neck (3.79%). Analysis of the MAUDE database found 428 adverse events, including pain (24.07%), lip weakness (0.44%), and lead tethering (1.64%). Facebook group members reported higher rates of lip weakness and lead tethering than recorded in the MAUDE database. These findings illustrate how diverse data sources, such as social media, can enhance our understanding of patient experiences and identify gaps in patient education with HNS therapy. NA Laryngoscope, 2024.

Difficulty Falling Asleep is Associated with Poorer Therapeutic Outcomes in Unilateral Hypoglossal Nerve Stimulation.

The coexistence of insomnia and obstructive sleep apnea (OSA) is very prevalent. Hypoglossal nerve stimulation (HGNS) is an established second-line therapy for patients suffering OSA. Studies investigating the effect of the different aspects of insomnia on the therapeutic outcome are largely missing. Therefore, this study aimed to understand the impact of the different aspects of insomnia on the therapeutic outcome under HGNS therapy in clinical routine. This is a retrospective study including 30 consecutive patients aged 55.40 ± 8.83 years (8 female; 22 male) undergoing an HGNS implantation in our tertiary medical center between 2020 and 2023. All patients underwent preoperative polysomnography (PSG) according to AASM. First follow-up PSG was performed 95.40 ± 39.44 days after activation (30 patients) and second follow-up PSG was performed 409.89 ± 122.52 days after activation (18 patients). Among others, the following PSG-related parameters were evaluated: apnea-hypopnea index (n/h) (AHI) and oxygen desaturation index (n/h) (ODI). Insomnia was assessed by the insomnia severity index (ISI) questionnaire. Preoperatively, all patients included filled out each ISI item. Spearman's-rho correlation coefficient was calculated for correlations. Preoperative score of ISI item 1 (difficulty falling asleep) was 1.93 ± 1.34 and preoperative cumulative ISI score (item1-7) was 18.67 ± 5.32. Preoperative AHI was 40.61 ± 12.02 (n/h) and preoperative ODI was 38.72 ± 14.28 (n/h). In the second follow-up, the mean difference in AHI was ∆ 10.47 ± 15.38 (n/h) and the mean difference in ODI was ∆ 8.17 ± 15.67 (n/h). Strong significant correlations were observed between ISI item 1 (difficulty falling asleep) and both ∆ AHI (r: -0.65, p=0.004) and ∆ ODI (r: -0.7; p=0.001) in the second follow-up. Difficulty falling asleep may hence negatively influence HGNS therapeutic outcome. Insomnia-related symptoms should be considered in the preoperative patient evaluation for HGNS.

Response to Hypoglossal Nerve Stimulation Changes With Body Mass Index and Supine Sleep

Hypoglossal nerve stimulation (HGNS) is a potential alternative therapy for obstructive sleep apnea (OSA), but its efficacy in a clinical setting and the impact of body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) on treatment response remain unclear. To investigate whether HGNS therapy is effective for patients with OSA, whether HGNS can treat supine OSA, and whether there are associations between BMI and treatment response. In this cohort study, adult patients with OSA implanted with HGNS at the Washington University Medical Center in St Louis from April 2019 to January 2023 were included. Data were analyzed from January 2023 to January 2024. HGNS. Multivariable logistic regression was performed to assess associations between HGNS treatment response and both BMI and supine sleep. Treatment response was defined as 50% reduction or greater in preimplantation Apnea-Hypopnea Index (AHI) score and postimplantation AHI of less than 15 events per hour. Of 76 included patients, 57 (75%) were male, and the median (IQR) age was 61 (51-68) years. A total of 59 patients (78%) achieved a treatment response. There was a clinically meaningful reduction in median (IQR) AHI, from 29.3 (23.1-42.8) events per hour preimplantation to 5.3 (2.6-12.3) events per hour postimplantation (Hodges-Lehman difference of 23.0; 95% CI, 22.6-23.4). In adjusted analyses, patients with BMI of 32 to 35 had 75% lower odds of responding to HGNS compared with those with a BMI of 32 or less (odds ratio, 0.25; 95% CI, 0.07-0.94). Of 44 patients who slept in a supine position, 17 (39%) achieved a treatment response, with a clinically meaningful reduction in median (IQR) supine AHI from 46.3 (33.6-63.2) events per hour preimplantation to 21.8 (4.30-42.6) events per hour postimplantation (Hodges-Lehman difference of 24.6; 95% CI, 23.1-26.5). In adjusted analysis, BMI was associated with lower odds of responding to HGNS with supine AHI treatment response (odds ratio, 0.39; 95% CI, 0.04-2.59), but the imprecision of the estimate prevents making a definitive conclusion. This study adds to the growing body of literature supporting the use of HGNS for OSA treatment. Sleep medicine clinicians should consider informing patients that higher BMI and supine sleeping position may decrease therapeutic response to HGNS. Future research is needed to replicate these findings in larger, more diverse cohorts, which would facilitate the optimization of treatment strategies and patient counseling for HGNS therapy.

Improved levels of checkpoint molecule PD-L1 on peripheral blood monocyte subsets in obstructive sleep apnea syndrome patients upon hypoglossal nerve stimulation.

Oxidative stress in patients suffering from obstructive sleep apnea syndrome (OSAS) is associated with a low-grade systemic inflammation, immune disturbance, and increased invasion of monocytes into the endothelium. Besides continuous positive airway pressure (PAP), hypoglossal nerve stimulation (HNS) has become a promising treatment option for patients with OSAS. We aimed to analyse the influence of HNS therapy on the cellular characteristics relevant for adhesion and immune regulation of circulating CD14/CD16 monocyte subsets. Whole blood flow cytometric measurements were performed to analyse the expression levels of different adhesion molecules and checkpoint molecule PD-L1 (programmed death-ligand 1) in connection with pro-inflammatory plasma cytokine IL-8 and the clinical values of BMI (body mass index), AHI (apnea-hypopnea index), ODI (oxygen desaturation index), and ESS (Epworth sleepiness scale) upon HNS treatment. Hypoglossal nerve stimulation treatment significantly improved the expression of adhesion molecule CD162 (P-selectin receptor) on non-classical monocytes and significantly downregulated the expression of PD-L1 on all three monocyte subsets. We conclude that the holistic improvement of different parameters such as the oxygenation of the peripheral blood, a reduced systemic inflammation, and the individual sleeping situation upon HNS respiratory support, leads to an improved immunologic situation.

Hypoglossal Nerve Stimulation and Cardiovascular Outcomes for Patients With Obstructive Sleep Apnea

Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA). To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function. This double-blind, sham-controlled, randomized crossover therapy trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the trial. Data analysis was performed from January to September 2022. Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values. The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points. Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment. In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials. ClinicalTrials.gov Identifier: NCT03359096.

Clinical Applicability of Ultrasound Shear Wave Elastography in Patients under Hypoglossal Nerve Stimulation Therapy

Relationship between stiffness of genioglossi (GG) and geniohyoidei (GH) muscles under electric hypoglossal nerve stimulation therapy (HNS) in relation to success of therapy was investigated with additional special focus on tongue movement. Patients and Methods: Clinical and sleep laboratory parameters of a cohort of 18 patients with known shear wave velocity (SWV) data of the ipsilateral and contralateral musculi GG and GH (sGG, sGH and nGG, nGH) before and under HNS therapy were analyzed. The SWV was already determined using the ultrasonic shear wave elastography (US-SWE) technique. Results: Median Epworth Sleepiness Scale (ESS) was 8 (IQR 12), median baseline Apnoe–Hypopnoe Index (AHI) 31.65 (IQR 25.1), median AHI under HNS therapy 16.3 (IQR 20.03). Therapy success: 9/18 patients (AHI during therapy &lt; 15/h). There was no significant difference in SWV (sGG, sGH, nGG and nGH) between therapy responders and non-responders during therapy. Also, no difference could be seen with respect to the difference and increase in SWV values without and with stimulation. Examination of SWV values (sGG, sGH, nGG, nGH during stimulation, difference of SWV values stimulation − no stimulation, increase factor of SWV) revealed a significant negative correlation between the AHI under therapy and the measured SWV of the musculus GH of the contralateral side during stimulation (−0.622, p = 0.006). Patients with bilateral protrusion of the tongue differed regarding to therapy success in increase in SWV in sGG (p = 0.032). Tongue protrusion to contralateral: A significant difference between patients with AHI during therapy &lt; 15/h in SWV values at sGG without stimulation (p = 0.021) was seen, with also a correlation to the current AHI under therapy (p = 0.047) and the change factor of the AHI (p = 0.015). Conclusion: Stiffness of the target muscle does not appear to be an isolated measure of the success of HNS therapy. This observation may have implications for future decision-making processes in the process of titrating electrical therapy parameters. But the technique of US-SWE may be useful for future research of the neurophysiology of the tongue and OSA phenotyping.

Increased Body Mass Index Correlates with Less Favorable Postoperative Outcomes After Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea: A Retrospective Cohort Study

Obstructive sleep apnea is associated with high morbidity. Hypoglossal nerve stimulation (HNS) has become a novel (neuro-) surgical treatment strategy for obstructive sleep apnea, demonstrating good success rates. Beyond predefined inclusion and exclusion criteria, no precise data are available, enabling individual preoperative risk assessment. To improve preoperative risk stratification, this study analyzed individual patient factors that affect outcomes of HNS. Fourteen patients treated with unilateral HNS were analyzed retrospectively. Assessed risk factors included: hypertension, diabetes mellitus, depression, smoking, alcohol consumption, body mass index (BMI), and disease duration. Treatment success was defined as a reduction in the postoperative apnea-hypopnea index (AHI) to≤20 events/hour, with a relative reduction of at least 50% compared to baseline. A significant reduction in the postoperative apnea-hypopnea index was observed in all patients (P < 0.0001). BMI correlated significantly with postoperative AHI scores (95% confidence interval, 0.1519-0.8974; P= 0.018). Significant treatment success was observed in 50% of patients. Compared with the "Excellent Responder group," the "Responder group" demonstrated a significantly higher BMI (95% confidence interval, 1.174-6.226; P= 0.0078). Diabetes, hypertension, disease duration, smoking, depression, and alcohol consumption were not significantly associated with AHI reduction. Our findings suggest that BMI may be an independent risk factor for the response to HNS, with patients who had less benefit from therapy having significantly higher BMI than "Excellent Responders." Therefore, carefully selecting patients is crucial in obtaining optimal outcomes with HNS therapy, especially those with a high BMI.

Patient-reported experience with hypoglossal nerve stimulation in the treatment of obstructive sleep apnea

BackgroundBreathing-synchronized hypoglossal nerve stimulation (HNS) is routinely used as an alternative treatment for patients with obstructive sleep apnea (OSA). Significant and clinically relevant improvements in disease severity and OSA symptoms such as daytime sleepiness as well as overall quality of life have been reported in randomized-controlled trials and large real-world cohort studies. However, so far, few data exist on patient-reported experience with the treatment.MethodsA structured survey with 22 questions was constructed using five-level Likert scales (1 = no agreement, 5 = complete agreement) to evaluate patient experience with HNS and perception of the treatment in the domains “Overall experience with therapy,” “Experience with treatment process,” and “Side-effects from treatment.” Additional data were collected on current symptom status, measured with Epworth sleepiness scale (ESS) questionnaire, and OSA disease history. Multiple linear regression analysis was conducted to test associations of medical variables and response behavior. Correlations between variables and domains, as well as individual items, were assessed using Spearman rank test.ResultsA total of 75 patients from Germany who were treated with breathing-synchronized HNS were enrolled (mean age 57.3 years, 78% male), and 71 questionnaires with complete data were included for analysis. Two-thirds of participants (67%) had a history of OSA history for 5 years or longer. Of all patients, 76% had normalized OSA symptoms at time of the study (ESS: 6.4 ± 5.0) and 98% reported using stimulation therapy every night. Regression analysis revealed an association of current symptoms measured with ESS and response behavior. Hence, patients with normalized daytime sleepiness reported significantly more positive experience across all domains assessed, compared to patients with residual daytime sleepiness. Overall, only 2% of participants reported side effects that made them reduce or discontinue stimulation therapy. The rate of reported side effects was associated with current symptom control under therapy.ConclusionsOverall patient-reported experience with breathing-synchronized HNS therapy was positive and high satisfaction with the treatment process was observed. Side effects occurred, but rarely affected subjective use of the therapy or satisfaction. Subjective experience and perception are influenced by residual daytime sleepiness with stimulation therapy.

Hypoglossal Nerve Stimulation Therapy Outcomes in Apnea- Versus Hypopnea-Predominant Patients.

The influence of apnea- and hypopnea-predominance on hypoglossal nerve stimulation therapy outcomes (HGNS) is still poorly defined. We assessed the significance of apnea- and hypopnea-predominance in HGNS outcomes. Case series with chart review. Single-institution tertiary care center. A total of 216 subjects were included, all of which had undergone drug-induced sleep endoscopy (DISE) and HGNS implantation. Demographic and polysomnographic data were collected. The 4% apnea-hypopnea criteria were used to calculate apnea-hypopnea index (AHI). Central apneas were omitted. Univariate logistic and linear regression were used to study the association between these data and apnea-predominance and hypopnea-predominance. Kruskal-Wallis rank sum test was used to compare medians between groups for DISE collapse patterns. Sixty-three patients were apnea-predominant, and 153 patients were hypopnea-predominant. These 2 groups were similar demographically (p > .20). There was no significant difference in HGNS outcomes between the groups assessed using Sher20 criteria at the 1-year mark using all-night, single-setting polysomnography or home sleep studies. Apnea index (AI)/AHIand reduction in AHI from preoperative to titration were significantly associated (p = .046). The median preoperativehypopnea index was significantly lower (p = .033) in subjects with no oropharyngeal collapse than patients with partial or complete oropharyngeal collapse. There were no significant relationships between AI/AHI and the different degrees of collapse at the velopharynx, oropharynx, tongue base, or epiglottis. In line with CPAP, tonsillectomy, and mandibular advancement therapy studies, we found there was largely no significant difference in DISE anatomy or in HGNS treatment outcomes between apnea- and hypopnea-predominant individuals.

Patient-reported outcomes with hypoglossal nerve stimulation for treatment of obstructive sleep apnea: a systematic review and meta-analysis.

Hypoglossal nerve stimulation (HNS) has recently been introduced as an alternative treatment for patients with OSA. A large number of studies have demonstrated substantial changes in OSA with this therapy by reducing respiratory events and improving symptoms such as daytime sleepiness and quality of life. The objective of this review was to conduct a systematic review and meta-analysis to evaluate patient-reported outcomes and experience with HNS therapy. A systematic literature search of MEDLINE, Cochrane, and Web of Science was performed to identify randomized controlled and observational studies reporting subjective outcomes with different HNS systems in patients with OSA. Abstracts of 406 articles were screened and a subset of 55 articles were reviewed for eligibility. Risk of bias was assessed using the ROBINS-I tool. Meta-analysis using RevMan was performed when > 2 studies were identified that reported data on a specific outcome. Thirty-four publications reporting data on 3785 patients with a mean follow-up of 11.8 ± 12.2months were identified and included in the meta-analysis. The analysis revealed a pooled effect of 4.59 points improvement in daytime sleepiness as measured by the ESS questionnaire (Z = 42.82, p < .001), 2.84 points improvement in daytime functioning as measured by the FOSQ score (Z = 28.38, p < .001), and 1.77 points improvement in sleep quality as measured by the PSQI questionnaire (Z = 2.53, p = .010). Patient-reported experience was consistently positive and revealed additional relevant aspects from this perspective. HNS therapy significantly improves quality of life in patients with OSA and reliably produces clinically meaningful effects on daytime sleepiness, daytime functioning, and sleep quality. Treatment regularly meets or exceeds the minimum clinically important differences defined for the respective instruments. Additional research is needed to further investigate effects on quality of life beyond improvements in daytime sleepiness and daytime functioning.

0459 Cardiovascular Endpoints for Obstructive Sleep Apnea with Twelfth Nerve Stimulation: Measures of Sleep-Related Function

Abstract Introduction Obstructive sleep apnea (OSA) is an increasingly prevalent sleep-related breathing disorder linked to cognitive dysfunction and daytime sleepiness. Positive airway pressure (PAP) therapy, the first-line treatment for OSA, may improve cognitive function and sleepiness, but responses vary. Hypoglossal nerve stimulation (HGNS) is a novel and effective PAP alternative, but its effect on mitigating cognitive decline secondary to OSA is unknown. In the first sham-controlled HGNS trial, we evaluated the effect of HGNS therapy on cognitive measures and patient-reported outcomes (PROs) in patients with moderate-severe OSA. Methods In a double-blind, sham-controlled, randomized crossover therapy trial, patients already stabilized on HGNS therapy underwent four weeks of active and four weeks of sham HGNS, each with a 1-week washout period. Sham therapy was defined as the lowest voltage at which HGNS was sensed by the patient or visualized by the clinician. Cognitive measures (Psychomotor Vigilance Test [PVT], Digit Symbol Substitution Task [DSST]) and sleep-related PROs (Epworth Sleepiness Scale [ESS], Snoring Visual Analog Scale [VAS], Insomnia Severity Index [ISI], Functional Outcomes of Sleep Questionnaire [FOSQ]) were assessed after each 4-week period and compared between active and sham therapy. Results Sixty randomized patients were included. On average, participants were elderly (67.3±9.9 years), overweight (BMI 28.7±4.6 kg/m2) and had severe OSA prior to HGNS therapy (AHI 33.1±14.9 events/hour). Patients’ AHI decreased to 23.0±15.6 events/hour with sham therapy (p=0.0001) and 18.1±14.8 events/hour with active therapy (p&amp;lt; 0.0001), with a 4.9 event/hour decrease between active and sham therapy (p=0.014). There were no significant differences in performance measures on PVT or DSST between active and sham HGNS. All sleep-related PROs were statistically significant with moderately large (effect sizes ~0.41-0.56) improvements following active HGNS. Conclusion The HGNS system permits a unique investigation of the therapy “on/off” effect on measures of cognitive function. In the first sham-controlled, randomized crossover trial of patients using HGNS, all sleep-related PROs, but not objective measures of cognition, were significantly different between sham and active (therapeutic) levels. These findings warrant additional investigation examining the relationship between subjective and objective measures of function in OSA. Support (if any) American Heart Association (17SDG33670349) American Sleep Medicine Foundation (176-JF-17) National Institutes of Health (P01-HL094307)

1024 A Challenging Inspire Case: All Roads Do Not Necessarily Lead to Rome

Abstract Introduction Hypoglossal nerve stimulation (HNS) for the treatment of obstructive sleep apnea (OSA) in patients who have failed positive airway pressure (PAP) therapy for one reason or the other is now standard of care. Once the device is implanted and activated, voltage to stimulate the nerve has to be titrated over time, ultimately leading to an HNS titration study. There are 4 possible electrode configurations to stimulate different fibers in the nerve that can be employed for treatment. We present a case of a patient who was a challenge with worsening of OSA with Inspire. Report of case(s) A 65-year-old woman with hypertension, and severe OSA, intolerant of positive airway pressure or oral appliances was implanted with Inspire. Post activation, there was symptomatic improvement with reduction of overall apnea-hypopnea index (AHI) from 34 per hour of sleep to 6.3 per hour. However, patient slept exclusively on the sides with evidence of significant residual disease in REM sleep. During subsequent weeks, patent reported inability to restrict position and discomfort and anxiety associated with up titration. Both awake endoscopy and advanced overnight HNS titration were pursued. All 4 electrode configurations were tested during both procedures. With the exception of (minus-plus-minus) configuration, there was worsening of sleep disordered breathing and higher residual AHI of 60 per hour on polysomnography and evidence of poor tongue motion and collapsed velopharynx on awake endoscopy. Inspire settings were readjusted to (minus-plus-minus) configuration with instructions for very slow outpatient uptitration and co-management of anxiety and discomfort with anxiolytics and sleep aids. Conclusion We make two important conclusions from this case. Firstly, although there are established criteria for patient selection for hypoglossal nerve stimulation therapy, certain other factors that impact success which are not as easily defined include the patients’ expectations, tolerance of discomfort, propensity to anxiety and personality type which impact the ability to successfully titrate voltage with the Inspire device over time. Secondly, as the tongue is a complex muscle, both under titration and over titration may be counterproductive and additionally, electrode configuration may also have varying effects on tongue protrusion and impact success. Support (if any)

0479 Prevalence, Clinical Features, and Impact of Low Respiratory Arousal Threshold on Patients with Hypoglossal Nerve Stimulation

Abstract Introduction This study aims to explore the prevalence and clinical features associated with low respiratory arousal threshold (ArTH) amongst patients with hypoglossal nerve stimulation (HNS) for the treatment of obstructive sleep apnea (OSA) and the possible effects it has on HNS adherence and device usage between time of activation and 1-year post-activation. Methods Following institutional review board approval, consecutive patients who underwent HNS system implantation were retrospectively studied, including clinical characteristics, diagnostic polysomnography (PSG) or homes sleep apnea test (HSAT) and HNS post-implant data. Inclusion criteria were patients with ≥1 year of HNS usage who had also completed a post-implant HNS PSG titration study. Results Forty-five patients met inclusion criteria. Low ArTH was present in 44.4% of patients and compared to those with high ArTH, low ArTH had a higher prevalence of restless leg syndrome (RLS) (45% vs 12%, p&amp;lt; 0.05) and depression (60% vs 28%, p&amp;lt; 0.05). Low ArTH exhibited a trend toward shorter diagnostic total sleep time (TST) (295.0 vs 373.3 minutes, 0.05 &amp;lt; p &amp;lt; 0.1). Bivalent logistic regression indicated the odds of having low ArTH is 8.6 times greater in patients with RLS (OR 8.6, CI 1.1 – 68.6, p&amp;lt; 0.05). Across all time points, low ArTH resulted in lower mean percentage of HNS nights used (92% vs 86%, p&amp;lt; 0.001) and a lower HNS amplitude (2.41 V vs 1.96 V, p&amp;lt; 0.001) and demonstrated a trend towards lower percentage of nights used ≥4 hours (72.9% vs 66.1%, 0.05 &amp;lt; p &amp;lt; 0.1). 1-year post activation, low ArTH patients continued to show lower percentage of HNS nights used (89.8% vs 75.6%, p&amp;lt; 0.01) and a lower HNS amplitude (2.3 V vs 1.9 V, p&amp;lt; 0.01). Conclusion Low ArTH was highly prevalent amongst patients with OSA treated with HNS and was more frequently associated in patients with RLS. Patients with a low ArTH demonstrated significantly lower percentage of nights used and lower amplitudes, indicating the importance this particular phenotype may play in patient compliance with HNS. These findings could help better select candidates who will tolerate HNS therapy and develop targeted therapies to improve long-term adherence. Support (if any)

0515 Awake endoscopy optimizes tolerance and effectiveness of hypoglossal nerve stimulation

Abstract Introduction Hypoglossal nerve stimulation(HGNS) which has been available and FDA approved since 2014 in the US may allow for effective treatment of obstructive sleep apnea(OSA) in patients without concentric collapse on Drug induced Sleep Endoscopy and other clinical parameters who have failed CPAP. Tolerance of the stimulation parameters may be problematic in a subset of patients not allowing them to adhere to the therapy. Although there are not currently clinically authoritative studies regarding the role of awake endoscopy in management of such patients, visualizing what comfortable settings that allow for effective tongue protrusion while awake potentially allowing for effective treatment of upper airway obstruction in the office setting might serve as a surrogate for ensuring optimization of such treatment during patients' sleep and this is a retrospective review of such patients at Tufts Medical Center in Boston MA. Methods A retrospective chart review of patients who were implanted with a HGNS device (Inspire TM) who did not tolerate therapy and proceeded to awake endoscopy to optimize therapy settings that allowed tolerance or comfort of stimulation were analyzed. Patients who had HGNS and awake endoscopy as part of clinical assessment at any time during the course of their clinical evaluations were included in the review. Results Out of 129 patients implanted at Tufts Medical Center in Boston, MA, 13 such patients (Approximately 10 % of the total number of HGNS implanted patients) proceeded to awake endoscopy to optimize therapy as noted above. A subset of these patients had improved adherence to therapy and treatment of OSA with HGNS therapy subsequently to such management. Conclusion A subset of patients may remain adherent to HGNS therapy after strategically performing awake endoscopy for ensuring comfort and adequacy of tongue protrusion during awake endoscopy in the outpatient setting. This retrospective review indicates that awake endoscopy may optimize tolerance and adherence of HGNS therapy for treatment of OSA in selected patients. Support (if any) None

0535 Impact of hypoglossal nerve stimulation surgery alone on sleep disordered breathing and sleepiness

Abstract Introduction Hypoglossal Nerve Stimulation (HNS) is an established option for CPAP -intolerant obstructive sleep apnea (OSA) patients, with multiple studies demonstrating safety and effectiveness. There are known nightly variations in OSA severity. We aimed to determine if device implant alone (with therapy off) compared to baseline influenced sleep disordered breathing and daytime sleepiness. Methods This was a retrospective analysis of the STAR (Stimulation Therapy for Apnea Reduction) Trial, conducted from 2010-2016, that led to FDA approval HNS. Data was collected at a pre-implant screening, and post-implant prior to device activation (therapy off). Each visit included an attended polysomnography (PSG) and Epworth Sleepiness Scale (ESS). PSGs were scored by a central core lab. Results There were 126 participants (83% male), age 55 ± 10 years. The time between pre-implant baseline screening and device activation visit averaged 88 ± 29 days. BMI was 28 ± 3 at baseline and 28 ± 3 post-implant with therapy off. The pre and post-implant Apnea Hypopnea Index (AHI)s were similar (32 ± 9 vs 32 ± 9 events/hour, p=0.82). The two-night AHI ranged from 13 to 65. The average AHI change between pre-implant and post-implant (therapy off) was -0.3 ± 17 events/hour. The Sher 20 response rate between pre-implant and post-implant therapy off was 13%. By comparison, previously published mean AHI with therapy activated was approximately 10-15 events/hour, and Sher 20 response rates ranged between 65%-75%. ESS pre and post-implant (therapy off) were similar (12 ± 5 vs 11 ± 5, p=0.09), compared to ESS previously reported with HNS therapy activated (typically 6-7). Conclusion The STAR two-night baseline AHIs ranged between 13-65. While there were nightly differences in AHI in some patients, surgical implant of HNS with therapy off, did not result in meaningfully improvement in the AHI, Sher 20 response rate, or ESS. Support (if any) Inspire Medical Systems