Upper Airway Stimulation Therapy Research Articles

Upper airway stimulation therapy and sleep architecture in patients with obstructive sleep apnea.

To quantify changes in sleep architecture before and after upper airway stimulation (UAS) therapy in patients with obstructive sleep apnea. Retrospective chart review. This study was performed at a single-institution tertiary academic care center. Patients who responded successfully to UAS implantation were selected for this study. Preoperative and postoperative sleep studies were compared to determine sleep architecture changes. Primary outcomes included sleep architecture parameters such as N1, N2, N3, and rapid eye movement (REM) in addition to others. Secondary outcomes included body mass index. Thirty-five patients met inclusion criteria for this study. There was significant improvement across several sleep architecture parameters. N1 sleep percent decreased from 16.7% ± 2.1% preoperatively to 10.1% ± 1.6% postoperatively (P = .023). Time spent in N2 increased from 148.0 ± 12.4 minutes to 185.5 ± 10.4 minutes (P = .030), whereas N3 increased from 21.9 ± 5.0 minutes to 57.0 ± 11.1 minutes (P = .013). No significant changes were observed in REM sleep. Arousal index decreased from 38.8 ± 4.0 to 30.3 ± 4.0 (P = .050). There was significant improvement across several sleep architecture parameters among patients who responded successfully to UAS implantation. 4 Laryngoscope, 130:1085-1089, 2020.

0572 Impact of Upper Airway Stimulation Therapy on Clinical Blood pressure Parameters from the ADHERE Registry

0572 Impact of Upper Airway Stimulation Therapy on Clinical Blood pressure Parameters from the ADHERE Registry

Clinical and Economic Benefits of Upper Airway Stimulation for Obstructive Sleep Apnea in a European Setting

Background: Upper airway stimulation (UAS) is a treatment approach for patients with moderate-to-severe obstructive sleep apnea who cannot adhere to continuous positive airway pressure therapy. Objective: The objective was to evaluate added patient benefit and cost-effectiveness of UAS in the German health care system. Methods: We used a decision-analytic Markov model to project major adverse cardiovascular or cerebrovascular events (myocardial infarction [MI] or stroke), motor vehicle collision (MVC), mortality, quality-adjusted life years (QALYs), and costs. The assumed reduction in the apnea-hypopnea index with UAS compared to no treatment is based on German real-world data. Other input data were derived from the literature, public statistics, and multivariate regression. Cost-effectiveness was evaluated in Euros per QALY gained, both discounted at 3%. Results: UAS was projected to reduce event risks (10-year relative risk for stroke, MI, cardiovascular death, and MVC: 0.76, 0.64, 0.65, and 0.34, respectively), and to increase survival by 1.27 years. While the UAS strategy incurred an additional 1.02 QALYs within the patient lifetime, there were also additional costs of EUR 45,196, resulting in an incremental cost-effectiveness ratio of EUR 44,446 per QALY gained. ­Conclusions: In the present model-based analysis, UAS therapy provides meaningful benefit to patient-relevant endpoints and is a cost-effective therapy in the German setting.

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

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. 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. The study population after implantation of UAS device consisted of ten Caucasian males with a mean age of 51.9 ± 11.8years, 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. 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.

Addressing the Tone and Synchrony Issue During Sleep: Pacing the Hypoglossal Nerve.

Upper airway stimulation is a novel therapy for patients suffering from obstructive sleep apnea who are incompliant toward continuous positive airway pressure therapy. Evidence supporting the effectiveness of this therapy with regard to the treatment of disordered breathing, subjective daytime impairment, and its effect on sleep characteristics has increased. Information on the subjective sensation of the stimulation of the hypoglossal nerve could be gathered as more patients are implanted and knowledge of different aspects of the therapy is increasing. Comparisons between upper airway stimulation therapy and other surgical treatment options have been conducted. The surgical technique could be further optimized.

Post-approval upper airway stimulation predictors of treatment effectiveness in the ADHERE registry.

Upper airway stimulation (UAS) has been shown to reduce severity of obstructive sleep apnoea. The aim of this study was to identify predictors of UAS therapy response in an international multicentre registry.Patients who underwent UAS implantation in the United States and Germany were enrolled in an observational registry. Data collected included patient characteristics, apnoea/hypopnoea index (AHI), Epworth sleepiness scale (ESS), objective adherence, adverse events and patient satisfaction measures. Post hoc univariate and multiple logistic regression were performed to evaluate factors associated with treatment success.Between October 2016 and January 2018, 508 participants were enrolled from 14 centres. Median AHI was reduced from 34 to 7 events·h−1, median ESS reduced from 12 to 7 from baseline to final visit at 12-month post-implant. In post hoc analyses, for each 1-year increase in age, there was a 4% increase in odds of treatment success. For each 1-unit increase in body mass index (BMI), there was 9% reduced odds of treatment success. In the multivariable model, age persisted in serving as statistically significant predictor of treatment success.In a large multicentre international registry, UAS is an effective treatment option with high patient satisfaction and low adverse events. Increasing age and reduced BMI are predictors of treatment response.

Upper-Airway Stimulation Before, After, or Without Uvulopalatopharyngoplasty: A Two-Year Perspective.

Upper airway stimulation (UAS) is an effective second-line treatment for obstructive sleep apnea (OSA). In certain patients, there is a considerable need for advanced programming, notably with inadequate palatal response to therapy. The aim of the study was to investigate the impact of uvulopalatopharyngoplasty and tonsillectomy (UPPP-TE) on UAS therapy outcomes from a 2-year perspective after implantation. This study included all consecutive patients implanted with UAS in which a full set of 1- and 2-year follow-up assessments (M12 and M24) were obtained. Cases were analyzed in three groups: patients with UPPP-TE after (group 1) and before (group 2) UAS, and those without UPPP-TE (group 3). Therapy success could be achieved in about 80% of the entire cohort. Groups 2 and 3 did not differ significantly with regard to obesity, Apnea-Hypopnea Index, or Oxygen Desaturation Index. With regard to initial sleep endoscopy, there were fewer patients without any obstruction at the palatal and oropharyngeal levels and higher prevalence of lateral obstruction patterns at oropharynx in group 1 in contrast to groups 2 and 3. Groups 2 and 3 showed similar results, although group 2 patients underwent UPPP-TE before UAS implantation. UPPP-TE should be considered in patients with persistent OSA after UAS implantation if the obstruction is identified at the level of velum and oropharynx. Although this approach has higher response rates and better outcomes can be achieved in patients with UAS, there is no indication for patients to routinely undergo UPPP-TE prior to UAS implantation. 4 Laryngoscope, 129:514-518, 2019.

Evaluation of body position in upper airway stimulation for obstructive sleep apnea-is continuous voltage sufficient enough?

The definition of positional obstructive sleep apnea (POSA) is widely accepted as a difference of 50% or more in AHI between supine and non-supine position. Upper airway stimulation (UAS) is an effective treatment for OSA but the implant delivers a single voltage over sleep period without consideration of body position. Clinical practice suggests different outcomes for OSA in supine position under UAS treatment. Outcomes of 44 patients were analyzed 12months after implantation in a two-center, prospective consecutive trial in a university hospital setting. Total night and supine AHI were evaluated and the ratio of time spent in supine was considered. Correlation between the classic and the modified definition of POSA and treatment response were evaluated. The time ratio spent in supine position did not differ before implantation and after 12months. Total and supine AHI were reduced with the use of UAS therapy (p < 0.001) but both the baseline and final supine AHI were higher than total night AHI. Considering POSA definition as a ratio of supine to non-supine AHI, there was no clear cutoff for defining responders neither with nor without the additional component of time in supine position. The OSA reduction is strong for the total AHI and supine AHI. Nonetheless, here, there is no cutoff for defining POSA as critical for UAS therapy response. Therefore, there is no evidence for excluding POSA patients from UAS in general. Future technology improvement should take body position and adaptive voltage into account.

Upper Airway Stimulation in Patients With Obstructive Sleep Apnea and an Elevated Body Mass Index: A Multi-institutional Review.

An elevated body mass index (BMI) influences the severity of disease and treatment options utilized for obstructive sleep apnea (OSA). With this study, we aim to evaluate a cohort of patients undergoing upper airway stimulation (UAS) for treatment of OSA and assess the impact of BMI on surgical and quality of life outcomes. We designed a case-control, retrospective review, of all patients undergoing UAS at two academic institutions between 2014 and 2017. We compare those with an elevated BMI to those without. We included patients with moderate-severe OSA, who were unable to tolerate therapy with continuous positive airway pressure (CPAP), were treated with UAS, and had a postoperative sleep study performed. We evaluated postoperative sleep study data including apnea-hypopnea index (AHI), O2 desaturation nadir, rate of cure, and rate of success in those with an elevated BMI to those without an elevated BMI. Success was defined as a drop in the postoperative AHI by 50% compared to the preoperative value and to less than 20. We also assessed daytime sleepiness using the Epworth Sleepiness Scale. When defining an elevated BMI as greater than 32, we found no difference between elevated and nonelevated BMI cohorts in postoperative AHI, O2 desaturation nadir, daytime sleepiness, rate of surgical success, or rate of cure. Patients with obstructive sleep apnea, unable to tolerate CPAP, and with an elevated BMI can be successfully treated with upper airway stimulation therapy. 3. Laryngoscope, 128:2425-2428, 2018.

In Response to Upper Airway Stimulation Therapy and Prior Airway Surgery for Obstructive Sleep Apnea

In Response to <i>Upper Airway Stimulation Therapy and Prior Airway Surgery for Obstructive Sleep Apnea</i>

Upper Airway Stimulation for Obstructive Sleep Apnea: Results from the ADHERE Registry.

Objective Upper airway stimulation (UAS) is an alternative treatment option for patients unable to tolerate continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA). Studies support the safety and efficacy of this therapy. The aim of this registry is to collect retrospective and prospective objective and subjective outcome measures across multiple institutions in the United States and Germany. To date, it represents the largest cohort of patients studied with this therapy. Study Design Retrospective and prospective registry study. Setting Ten tertiary care hospitals in the United States and Germany. Subjects and Methods Patients were included who had moderate to severe OSA, were intolerant to CPAP, and were undergoing UAS implantation. Baseline demographic and sleep study data were collected. Objective and subjective treatment outcomes, adverse events, and patient and physician satisfaction were reviewed. Results The registry enrolled 301 patients between October 2016 and September 2017. Mean ± SD AHI decreased from 35.6 ± 15.3 to 10.2 ± 12.9 events per hour ( P < .0001), and Epworth Sleepiness Scale scores decreased from 11.9 ± 5.5 to 7.5 ± 4.7 ( P < .0001) from baseline to the posttitration visit. Patients utilized therapy for 6.5 hours per night. There were low rates of procedure- and device-related complications. Clinical global impression scores demonstrated that the majority of physicians (94%) saw improvement in their patients' symptoms with therapy. The majority of patients (90%) were more satisfied with UAS than CPAP. Conclusions Across a multi-institutional registry, UAS therapy demonstrates significant improvement in subjective and objective OSA outcomes, good therapy adherence, and high patient satisfaction.

Tongue motion variability with changes of upper airway stimulation electrode configuration and effects on treatment outcomes.

Upper airway stimulation (UAS) is an effective treatment for obstructive sleep apnea (OSA). Previous data have demonstrated a correlation between the phenotype of tongue motion and therapy response. Closed loop hypoglossal nerve stimulation implant offers five different electrode configuration settings which may result in different tongue motion. Two-center, prospective consecutive trial in a university hospital setting. Clinical outcomes of 35 patients were analyzed after at least 12 months of device use. Tongue motion was assessed at various electrode configuration settings. Correlation between the tongue motion and treatment response was evaluated. OSA severity was significantly reduced with the use of UAS therapy (P < .001). Changes in tongue motion patterns were frequently observed (58.8%) with different electrode configuration settings. Most of the patients alternated between right and bilateral protrusion (73.5%), which are considered to be the optimal phenotypes for selective UAS responses. Different voltage settings were required to achieve functional stimulation levels when changing between the electrode settings. UAS is highly effective for OSA treatment in selected patients with an apnea-hypopnea index between 15 and 65 events per hour and higher body mass index. Attention should be given to patients with shifting tongue movement in response to change of electrode configuration. The intraoperative cuff placement should be reassessed when tongue movement shifting is observed. 4 Laryngoscope, 1970-1976, 2018.

Upper airway stimulation therapy and prior airway surgery for obstructive sleep apnea.

To determine if patients with prior airway surgery for obstructive sleep apnea (OSA) had increased benefit following implantation with hypoglossal nerve stimulator. Retrospective chart review at a single institution tertiary academic care center. Following implantation with hypoglossal nerve stimulator device, the outcomes of patients who underwent prior airway surgery for OSA were compared with those who did not. Primary outcome measures included apnea-hypopnea index (AHI) and nadir oxyhemoglobin saturation (NOS) as measured by polysomnography. Secondary outcome measures included Epworth Sleepiness Scale. Forty-seven patients underwent implantation with hypoglossal nerve stimulator. Of these, 30 patients had undergone prior airway surgery for OSA, whereas 16 did not. Mean preoperative AHI and NOS were 39.3 ± 2.8 and 78% ± 1.8% for all patients, 39.4 ± 3.7 and 79% ± 14% for patients with prior airway surgery, and 39.1 ± 4.0 and 77% ± 2.6% for patients without prior surgery. Mean postoperative AHI and NOS were 3.9 ± 1.2 and 91% ± 0.4% for all patients, 4.2 ± 1.7 and 91% ± 0.5% for patients with prior surgery, and 3.4 ± 1.5 and 93% ± 0.6% for patients without prior surgery (P = 0.756 and 0.053, respectively). Overall, patients had significant improvement following implantation with hypoglossal nerve stimulator. Prior airway surgery had no statistically significant effect on postoperative AHI or NOS. 4. Laryngoscope, 128:1486-1489, 2018.

Development of a Clinical Pathway and Technical Aspects of Upper Airway Stimulation Therapy for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common disease with high morbidity and related mortality. Narrowing and collapse of the pharyngeal airway during sleep characterize the disease, resulting in a decrease (hypopnea) or a complete cessation (apnea) of oronasal airflow. Upper airway stimulation (UAS), using electrical neurostimulation of the hypoglossal nerve (n. XII) synchronized with ventilation, is a novel, evolving treatment option. UAS was found to be an effective treatment in CPAP-intolerant patients. The treatment success is partly due to the strict selection of the patients, based on previous findings. Furthermore, post-operative follow-up is needed in order to maintain or improve treatment outcome. Therefore, a clinical pathway, which provides structure and standardization, is crucial. In this paper, the aim is to discuss the technical aspects of UAS therapy and to describe a clinical pathway to organize the care process of UAS for OSA in a structured and standardized way.

Application of drug-induced sleep endoscopy in patients treated with upper airway stimulation therapy.

ObjectiveTo determine the level of agreement among experienced operators of candidacy for upper airway stimulation (UAS) based on evaluation of drug-induced sleep endoscopy (DISE).MethodsThe trial was designed as a single-blinded cross-sectional study. Four otolaryngologists with extensive DISE experience were given 63 video clips from the STAR trial video library. These videos were graded using the VOTE classification. Percentage agreement and Cohen’s κ (for inter-rater reliability) were calculated between pairs of reviewers, assessing palatal complete concentric collapse (CCC) and determining UAS eligibility. Subjects were also grouped based on collapse severity for each reviewer.ResultsThe reviewers had excellent (approximately 90%) agreement on findings at the level of the soft palate and tongue base. The inter-rater reliability for palatal CCC ranged from moderate to substantial. The agreement on determining the criteria for UAS implantation ranged from poor to moderate. All 4 upper airway structures as classified by the criteria of the VOTE were graded by all the reviewers as contributing to obstruction in a majority of subjects who were performed via application of DISE.ConclusionApplication of DISE remains a subjective examination, even among those experienced operators, therefore more studies need to be performed for evaluation of improvement in inter-rater reliability after implantation of training videos.

Selective upper airway stimulation for obstructive sleep apnea: a single center clinical experience

Selective upper airway stimulation (UAS) is a novel therapy for patients with obstructive sleep apnea (OSA). The aim of this study was to analyze the application and outcome of UAS in patients with moderate to severe OSA in the clinical routine of a tertiary referral center. The design of this study is single-center, prospective clinical trial. Thirty-one patients who received a UAS device (Inspire Medical Systems) were included. Treatment outcome was evaluated at 2, 3, 6, and 12months after surgery. Data collection included demographics, body mass index (BMI), apnea hypopnea index (AHI), oxygen saturation and desaturation index (ODI), Epworth Sleepiness Score (ESS), adverse events, and adherence to therapy. Sher criteria were used to evaluate treatment response. The mean age was 59.6years with thirty patients being male. Mean BMI was 28.8kg/m2. The mean pre-implantation AHI of 32.9/h could be reduced to 7.1/h after 12months (p<0.001). The mean pre-implantation ODI of 30.7/h could be reduced to 9.9/h after 12months (p=0.004). The mean pre-implantation ESS of 12.6 could be reduced to 5.9 after 12months (p=0.006). Serious adverse events did not occur. Therapy adherence was a usage of 6.6h/night after 12months. OSA severity and subjective daytime sleepiness were improved in patients with moderate to severe OSA after receiving UAS therapy. Patients maintained high adherence to therapy use after 12months. It is encouraging that UAS has been shown to be successfully implemented in the routine clinical management of OSA outside of a clinical trial setting.

Upper airway stimulation therapy: A novel approach to managing obstructive sleep apnea.

Review the role of upper airway stimulation (UAS) therapy in the management of moderate to severe obstructive sleep apnea (OSA). A literature search was performed of PubMed and Medline using the search terms clinical trial; obstructive sleep apnea; upper airway stimulation; hypoglossal stimulation; hypoglossal nerve; Inspire; and ImThera. All published clinical trials of currently available devices were reviewed. Unpublished data were excluded. UAS therapy results in surgical success (AHI decrease of >50% and overall AHI <= 20) in 66% of implanted subjects. In addition, UAS therapy results in significant improvement in daytime sleepiness, snoring, and sleep-related quality of life. UAS therapy is a valid alternative for select patients with moderate to severe OSA who are unsuccessful users of CPAP therapy. Laryngoscope, 126:S5-S8, 2016.

Long-Term Cost-Effectiveness of Upper Airway Stimulation for the Treatment of Obstructive Sleep Apnea: A Model-Based Projection Based on the STAR Trial.

Upper airway stimulation (UAS) is a new approach to treat moderate-to-severe obstructive sleep apnea. Recently, 12-month data from the Stimulation Treatment for Apnea Reduction (STAR) trial were reported, evaluating the effectiveness of UAS in patients intolerant or non-adherent to continuous positive airway pressure therapy. Our objective was to assess the cost-effectiveness of UAS from a U.S. payer perspective. A 5-state Markov model was used to predict cardiovascular endpoints (myocardial infarction [MI], stroke, hypertension), motor vehicle collisions (MVC), mortality, quality-adjusted life years (QALYs), and costs. We computed 10-year relative event risks and the lifetime incremental cost-effectiveness ratio (ICER) in $/QALY, comparing UAS therapy to no treatment under the assumption that the STAR trial-observed reduction in mean apnea-hypopnea index from 32.0 to 15.3 events/h was maintained. Costs and effects were discounted at 3% per year. U.S. healthcare system; third-party payer perspective. 83% male cohort with mean age of 54.5 years. UAS vs. no treatment. UAS substantially reduced event probabilities over 10 years (relative risks: MI 0.63; stroke 0.75; MVC 0.34), and was projected to add 1.09 QALYs over the patient's lifetime. Costs were estimated to increase by $42,953, resulting in a lifetime ICER of $39,471/QALY. Relative to the acknowledged willingness-to-pay threshold of $50,000-$100,000/QALY, our results indicate upper airway stimulation is a cost-effective therapy in the U.S. healthcare system.

The Influence of Drug‐Induced Sleep Endoscopy on Determining Candidacy for Upper Airway Stimulation Therapy

Objectives: (1) Determine the influence of drug-induced sleep endoscopy (DISE) on the surgical decision for upper airway stimulation (UAS) therapy. (2) Learn the limitations of drug induced sleep endoscopy. Methods: This was a single-blinded cross-sectional study in which 4 surgeons with extensive experience with DISE reviewed blinded DISE video clips from 63 patients who were screened for participation in the STAR (Stimulation Therapy for Apnea Reduction) trial, a phase III trial of upper airway stimulation (UAS) of the hypoglossal nerve for moderate-to-severe sleep apnea (OSA). Each DISE clip was independently reviewed and graded by a surgeon who then predicted whether the patient was a candidate for UAS therapy. Results: Evaluators demonstrated a high level of 100% agreement with regard to the presence of palatal collapse in 81% of cases, but less complete agreement concerning hypopharyngeal collapse (64% of cases). The viewers had complete agreement with regards to the presence or absence of circumferential airway collapse in 59% of cases. The surgeons had a low level of complete agreement (44% of cases; mean kappa 0.343) as to whether a given case was a good candidate for UAS therapy. Conclusions: DISE continues to be a highly subjective study. Previous evidence found that patients with circumferential airway collapse on DISE respond poorly to UAS. Additional training will be necessary in the future in order to increase agreement among surgeons as to which patients are the best candidates for UAS therapy.

Evaluation of Drug-Induced Sleep Endoscopy as a Patient Selection Tool for Implanted Upper Airway Stimulation for Obstructive Sleep Apnea

To study the possible predictive value of drug-induced sleep endoscopy (DISE) in assessing therapeutic response to implanted upper airway stimulation (UAS) for obstructive sleep apnea (OSA). During DISE, artificial sleep is induced by midazolam and/or propofol, and the pharyngeal collapse patterns are visualized using a flexible fiberoptic nasopharyngoscope. The level (palate, oropharynx, tongue base, hypopharynx/epiglottis), the direction (anteroposterior, concentric, lateral), and the degree of collapse (none, partial, or complete) were scored in a standard fashion. We report on the correlation between DISE results and therapy response in 21 OSA patients (apnea-hypopnea index [AHI] 38.5 ± 11.8/h; body mass index [BMI] 28 ± 2 kg/m(2), age 55 ± 11 y, 20 male/1 female) who underwent DISE before implantation of a UAS system. Statistical analysis revealed a significantly better outcome with UAS in patients (n = 16) without palatal complete concentric collapse (CCC), reducing AHI from 37.6 ± 11.4/h at baseline to 11.1 ± 12.0/h with UAS (p < 0.001). No statistical difference was noted in AHI or BMI at baseline between the patients with and without palatal CCC. In addition, no predictive value was found for the other DISE collapse patterns documented. The absence of palatal CCC during DISE may predict therapeutic success with implanted UAS therapy. DISE can be recommended as a patient selection tool for implanted UAS to treat OSA.