Obstructive sleep apnea (OSA) is characterized by recurrent apneas and hypopneas during sleep, leading to nocturnal hypercapnia, repeated oxyhemoglobin desaturations, and arousals.^1,2 It is highly prevalent, affecting 4% to 24% of men and 2% to 9% of women, as well as more than 50% of individuals with obesity.³ Obstructive sleep apnea is a major cause of morbidity and mortality.^4-8 It contributes to the development and progression of neurocognitive, metabolic, cardiovascular, and oncologic diseases,^7,9-16 as well as losses in workplace productivity, public safety, and related health care expenditures.^17-19 Nasal continuous positive airway pressure (CPAP) remains the mainstay of therapy for moderate to severe OSA. It relieves upper airway obstruction during sleep but does not reverse underlying defects in pharyngeal collapsibility. Poor adherence to CPAP severely limits its use,^20-22 and to our knowledge, few effective alternatives to CPAP exist.

Background: The remedē System Pivotal Trial was a prospective, multi-center, randomized trial demonstrating transvenous phrenic nerve stimulation (TPNS) therapy is safe and effectively treats central sleep apnea (CSA) and improves sleep architecture and daytime sleepiness. Subsequently, the remedē System was approved by FDA in 2017. As a condition of approval, the Post Approval Study (PAS) collected clinical evidence regarding long-term safety and effectiveness in adults with moderate to severe CSA through five years post implant. Methods: Patients remaining in the Pivotal Trial at the time of FDA approval were invited to enroll in the PAS and consented to undergo sleep studies (scored by a central laboratory), complete the Epworth Sleepiness Scale (ESS) questionnaire to assess daytime sleepiness, and safety assessment. All subjects (treatment and former control group) receiving active therapy were pooled; data from both trials were combined for analysis. Results: Fifty-three of the original 151 Pivotal Trial patients consented to participate in the PAS and 52 completed the 5-year visit. Following TPNS therapy, the apnea-hypopnea index (AHI), central-apnea index (CAI), arousal index, oxygen desaturation index, and sleep architecture showed sustained improvements. Comparing 5 years to baseline, AHI and CAI decreased significantly (AHI baseline median 46 events/hour vs 17 at 5 years; CAI baseline median 23 events/hour vs 1 at 5 years), though residual hypopneas were present. In parallel, the arousal index, oxygen desaturation index and sleep architecture improved. The ESS improved by a statistically significant median reduction of 3 points at 5 years. Serious adverse events related to implant procedure, device or delivered therapy were reported by 14% of patients which include 16 (9%) patients who underwent a pulse generator reposition or lead revision (primarily in the first year). None of the events caused long-term harm. No unanticipated adverse device effects or related deaths occurred through 5 years. Conclusion: Long-term TPNS safely improves CSA, sleep architecture and daytime sleepiness through 5 years post implant. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01816776.

Rationale: Ansa cervicalis stimulation (ACS) of the infrahyoid muscles has been proposed as a neurostimulation therapy for obstructive sleep apnoea (OSA). ACS stabilises the pharynx by pulling it caudally, but its specific effects on flow limitation caused by palatal, oropharyngeal lateral wall, tongue base, or epiglottis collapse remains unclear.Objectives: To quantify the effect of ACS on collapsibility of different pharyngeal flow-limiting structures.Methods: Participants with OSA underwent bilateral ACS during drug-induced sleep endoscopy. Maximum inspiratory airflow was assessed over a range of positive airway pressures while ACS was applied. The flow-limiting structure for each breath was classified based on manometric and endoscopic findings and a linear mixed-effects model characterised their response to ACS. The influence of patient characteristics was explored with univariate models.Measurements and main results: 41 participants yielded 1761 breaths for analysis. On average, bilateral ACS decreased the observed pharyngeal critical closing (P_CRIT) and opening (P_OPEN) pressures by −3.0 (95% CI −3.6–−2.3) and −3.7 (−4.4–−3.0) cmH₂O, respectively (p<0.001). During tongue base obstruction, modelled ACS effects forP_CRITandP_OPENwere −2.0 (−2.7–−1.4) and −3.1 (−3.8–−2.4) cmH₂O, respectively (p<0.001). Greater reductions were generally observed for other flow-limiting structures. A lower apnoea–hypopnea index was associated with a greater decrease inP_OPEN(p0.05).Conclusions: Bilateral ACS decreased collapsibility of all airway flow-limiting structures. ACS generally had greater effects on palatal, oropharyngeal lateral wall and epiglottic collapse than the tongue base.

Objective: To examine the accuracy and interrater reliability of a visually assessed vs airflow‐based measure of pharyngeal collapsibility obtained in patients with obstructive sleep apnea undergoing drug‐induced sleep endoscopy (DISE).Study Design: Prospective observational study.Setting: Academic tertiary care practice.Methods: Patients underwent DISE with airflow monitoring and nasal positive airway pressure titration to determine visual and airflow‐based levels of pharyngeal opening pressure (PhOP). Visual DISE‐PhOP was assessed by 2 blinded independent raters and defined as the pressure at which visual confirmation of airway collapse, including snoring, was abolished. Airflow‐based DISE‐PhOP was defined as the minimally effective positive airway pressure that abolished inspiratory flow limitation. Equivalence testing between visual and airflow DISE‐PhOP of each rater was performed with the two one sided T‐test (TOST) with an a priori equivalence bound of ±1 cm H₂O. Interrater reliability was evaluated with the intraclass correlation coefficient.Results: One hundred patients were enrolled in the study and 77 completed the full evaluation. The population was predominantly male (74%) with an average age of 54.8 years, body mass index of 30.1 kg/m², and apnea‐hypopnea index of 30.7 events/h. Equivalence testing showed that both raters were within ±1 cm H₂O of airflow‐based DISE‐PhOP (−0.43 to 0.09 cm H₂O and −0.32 to 0.48 cm H₂O). Interrater reliability of visual DISE‐PhOP between the raters was also good to excellent with an intraclass correlation coefficient of 0.895 (95% CI, 0.84‐0.932).Conclusion: DISE‐PhOP, a measure of upper airway collapsibility, was equivalent between airflow‐based and visual assessments with strong interrater reliability, supporting its adoption as a standardized objective parameter in clinical DISE.