The Whimsical Nature of Airway Obstruction during Drug-Induced Sleep Endoscopy.

A 47-year-old male patient diagnosed with severe obstructive sleep apnea (OSA) sought alternatives to positive airway pressure, prompting evaluation with drug-induced sleep endoscopy (DISE). He underwent a specialized DISE with nasal airflow and pharyngeal pressure monitoring. During obstructive apneas, airflow and pressure signals demonstrated dynamic, multilevel upper airway collapse, with shifting sites of airflow obstruction as respiratory effort increased. This case report illustrates how quantitative airflow and pressure measurements can complement the standard DISE exam and aid in surgical decision-making. Laryngoscope, 2024.

Association Between Soft Tissue Measures From Computed Tomography and Upper Airway Collapsibility on Drug-Induced Sleep Endoscopy.

OBJECTIVE: Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility. STUDY DESIGN: Cross-sectional analysis from a prospective cohort. SETTING: Academic medical center. METHODS: Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, PcritA) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either PcritA or PhOP. RESULTS: One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m2), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or PcritA, but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive PcritA (⍴ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures. CONCLUSION: After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis.

The Prevalence of Sentinel Central Events (SCent) During Drug-Induced Sleep Endoscopy.

OBJECTIVE: With the recent addition of airflow and respiratory effort channels, our group has observed central and mixed apnea events during drug-induced sleep endoscopy (DISE). We measured the frequency and timing of sentinel central and/or mixed events (SCents), as well as assessed for differences in velum, oropharynx, tongue, and epiglottis (VOTE) classification compared to obstructive events. STUDY DESIGN: Prospective single-cohort study. SETTING: Tertiary Care Academic Medical Center. METHODS: Patients underwent DISE between June 2020 and November 2022. Nasal airflow, thoracoabdominal effort belt signals, and videoendoscopy were simultaneously captured. Demographics, sleep study, and DISE data were compared among patients with and without SCents using Student's T tests or χ2 tests. RESULTS: On average, the cohort (n = 103) was middle-aged (53.5 ± 12.1 years), overweight (body mass index of 29.7 ± 5.3 kg/m2), and had severe obstructive sleep apnea (apnea-hypopnea index of 30.7 ± 18.7 events/h). Forty-seven patients (46%) were found to have at least 1 SCent. Among those with SCent, 45 (95.7%) transitioned to obstructive pathology after an average of 7.91 ± 2.74 minutes, with at least 95% of patients expected to do so within 12.57 minutes. Twenty-nine out of 47 patients (61.2% [95% confidence interval: 46.4.9%, 75.5%]) with SCent had meaningful differences between central/mixed and obstructive VOTE scores. CONCLUSION: Central events were present in almost half of our cohort. At least 95% of patients were expected to transition to obstructive events within 12 to 13 minutes of propofol initiation. In addition, over half of patients demonstrate significantly different VOTE scores between central and obstructive events. These factors should raise awareness of central events and scoring passive apneas during DISE and consider delaying VOTE scoring.

Airway Collapsibility during Drug-Induced Sleep Endoscopy Relates with Clinical Features of Obstructive Sleep Apnea.

INTRODUCTION: Increased pharyngeal collapsibility leads to obstructive sleep apnea (OSA). Positive airway pressure titration during drug-induced sleep endoscopy (DISE-PAP) provides objective collapsibility metrics, the pharyngeal opening pressure (PhOP), and active pharyngeal critical pressure (PcritA ). We examined the interrelationships between risk factors of OSA, airway collapsibility measures, and clinical manifestations of the disease. METHODS: This is a cross-sectional analysis of consecutive OSA patients undergoing DISE-PAP. Nasal PAP was increased stepwise until inspiratory flow limitation was abolished, signifying PhOP. PcritA was derived from the resulting titration pressure-flow relationships. Clinical data including demographics, anthropometrics, sleep studies, and patient-symptom questionnaires were obtained from the electronic medical record. Multivariate regression was used to evaluate the relationship between risk factors, airway collapsibility, and clinical data. RESULTS: On average, the 164 patients meeting inclusion criteria were middle-aged (54.2 ± 14.7 years), overweight/obese (BMI 29.9 ± 4.5 kg/m2 ), male (72.6%), White (79.3%) and had severe OSA (AHI 32.0 ± 20.5 events/hour). Mean PhOP was 7.5 ± 3.3 cm H2 O and mean PcritA was 0.80 ± 3.70 cm H2 O. Younger age (Standardized ß = -0.191, p = 0.015) and higher BMI (Standardized ß = 0.176, p = 0.028) were associated with higher PhOP, but not PcritA . PhOP and PcritA were both associated with AHI, supine AHI, and SpO2 nadir. Higher PhOP was associated with higher snoring scores (Standardized ß = 0.246, p = 0.008), but not other patient-reported outcomes. CONCLUSION: Objective assessment of passive and active airway mechanics during DISE relates with clinical risk factors for OSA. Quantitative measures of collapsibility provide accessible and meaningful data, enhancing the standard sleep surgery evaluation. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1978-1985, 2024.

The Application of Ultrasound to Quantify Hyoid Motion During Drug-Induced Sleep Endoscopy.

INTRODUCTION: The significance of hyoid dynamics in OSA pathophysiology remains unclear. Drug-induced sleep endoscopy (DISE) is often used for evaluating patients intolerant to positive airway pressure (PAP) therapy. We performed DISE with concurrent hyoid-focused ultrasonography to quantify hyoid dynamics during obstructive and non-obstructive breathing. METHODS: A cross-sectional analysis from a prospective cohort of patients undergoing DISE with PAP titration (DISE-PAP) and hyoid-focused ultrasound was conducted. Hyoid ultrasound was performed during obstructive breathing, and non-obstructive breathing after PAP administration. Motion was quantified by generating displacement curves based on echo-tracking hyoid movement. The image analysis protocol for quantifying hyoid displacement was performed independently by two researchers, and reliability of measures was assessed. Univariate and multivariate regressions were performed for various clinical data and hyoid displacement during obstructive breathing. RESULTS: Twenty patients met inclusion criteria. On average, the cohort was male (75%), elderly (65.9 ± 10 years), overweight (29.3 ± 3.99 kg/m2 ), and with moderate-to-severe OSA (29.3 ± 12.5 events/h). Mean hyoid displacement during obstructive breathing was 5.81 mm (±3.48). In all patients, hyoid displacement decreased after PAP administration (-3.94 mm [95% CI: -5.10, -2.78]; p < 0.0001). Inter-rater reliability for measures of hyoid displacement was excellent. After multivariate regression, hyoid displacement at baseline was associated with higher AHI (ß [95% CI] = 0.18 [0.03, 0.33], p = 0.020). CONCLUSION: During DISE, hyoid displacement is greater during obstructive breathing with significant variability amongst patients. Further, these ultrasonographic measurements had excellent intra- and inter-rater reliability. Additional, larger studies are needed to understand contributors to hyoid mobility. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3221-3227, 2023.

Targeted Hypoglossal Nerve Stimulation for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA). Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA. Design, Setting, and Participants: This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023. Intervention: Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively. Main Outcomes and Measures: Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale). Results: Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol. Conclusions and Relevance: This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI. Trial Registration: ClinicalTrials.gov Identifier: NCT02263859.

Transverse Maxillary Deficiency Predicts Increased Upper Airway Collapsibility during Drug-Induced Sleep Endoscopy.

OBJECTIVE: To examine the relationship between craniofacial skeletal anatomy and objective measures of pharyngeal collapse obtained during drug-induced sleep endoscopy. We hypothesized that transverse maxillary deficiency and an increased pharyngeal length will be associated with higher levels of pharyngeal collapsibility. STUDY DESIGN: Cross-sectional analysis in a prospective cohort. SETTING: University Hospital. METHODS: A cross-sectional analysis was conducted in a cohort of consecutive patients from the positive airway pressure (PAP) alternatives clinic who underwent computed tomography (CT) analysis and drug-induced sleep endoscopy for characterization of upper airway collapsibility. PAP titration was used to determine pharyngeal critical pressure (PCRIT ) and pharyngeal opening pressure (PhOP). CT metrics included: Transverse maxillary dimensions (interpremolar and intermolar distances) and pharyngeal length (posterior nasal spine to hyoid distance). RESULTS: The cohort (n = 103) of severe obstructive sleep apnea (Apnea and Hipopnea Index 32.1 ± 21.3 events/h) was predominantly male (71.8%), Caucasian (81.6%), middle-aged (54.4 ± 14.3 years), and obese (body mass index [BMI] = 30.0 ± 4.9 kg/m2 ). Reduced transverse maxillary dimensions were associated with higher PCRIT (intermolar distance: ß [95% confidence interval, CI] = -.25 [-0.14, -0.36] cmH2 O/mm; p = .03) and PhOP (Interpremolar distance: ß = -.25 [-0.14, -0.36] cmH2 O/mm; p = .02). Longer pharyngeal length was also associated with higher PCRIT (ß = .11 [0.08, 0.14] cmH2 O/mm, p = .04) and PhOP (ß [95% CI] = .06 [0.03, 0.09] cmH2 O/mm, p = .04). These associations persisted after adjustments for sex, age, height, and BMI. CONCLUSION: Our results further the concept that skeletal restriction in the transverse dimension and hyoid descent are associated with elevations in pharyngeal collapsibility during sleep, suggesting a role of transverse deficiency in the pathogenesis of airway obstruction.

Distinguishing central from obstructive hypopneas on a clinical polysomnogram.

Among sleep-related disordered breathing events, hypopneas are the most frequent. Like obstructive and central apneas, hypopneas may be obstructive or central (reduced drive) in origin. Nevertheless, unlike apneas, categorizing hypopneas as either "obstructive" or "central" is often difficult or ambiguous. It has been suggested that hypopneas could be categorized as obstructive when associated with snoring, inspiratory flow limitation, or paradoxical thoraco-abdominal excursions. This approach, however, has not been extensively tested and misclassification of hypopneas is unavoidable. Yet, much rides on the accurate distinction of these events to guide therapy with medical devices or pharmacological therapy in each patient. Additionally, accurate hypopnea classification is critical for design of clinical trials, because therapeutic responses differ depending on the subtype of hypopnea. Correctly classifying hypopneas can also allay concerns about obtaining coverage for therapies that specifically target either central or obstructive sleep-disordered breathing events. The present paper expands on the current criteria for differentiating obstructive from central hypopneas and provides illustrative tracings that can help classify these events. CITATION: Javaheri S, Rapoport DM, Schwartz AR. Distinguishing central from obstructive hypopneas on a clinical polysomnogram. J Clin Sleep Med. 2023;19(4):823-834.

Enhanced drug-induced sleep endoscopy: Distinguishing central from obstructive apnea.

This case report describes a patient originally diagnosed with obstructive sleep apnea (OSA) who was later found to have central sleep apnea (CSA) during drug-induced sleep endoscopy, which was subsequently confirmed on an in-laboratory sleep study. The revised diagnosis resulted in a change in recommended therapy from hypoglossal nerve stimulation to phrenic nerve stimulation. This case report is a reminder that the sleep surgeon must be cognizant of the possibility of CSA being misclassified as OSA especially as home sleep studies become increasingly routine, and discusses ways to more easily distinguish between CSA and OSA. Laryngoscope, 133:706-708, 2023.

The Accuracy and Reliability of Visually Assessed Pharyngeal Opening Pressures During Drug-Induced Sleep Endoscopy.

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 H2 O. 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 H2 O of airflow-based DISE-PhOP (-0.43 to 0.09 cm H2 O and -0.32 to 0.48 cm H2 O). 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.

Design and rationale for the treating Obstructive Sleep Apnea using Targeted Hypoglossal Nerve Stimulation (OSPREY) trial.

Obstructive sleep apnea (OSA) affects nearly 1 billion people worldwide, including approximately 35 million US residents. OSA has detrimental cardiovascular and neurocognitive consequences. Positive airway pressure corrects sleep disordered breathing but is not always tolerated or used sufficiently. Oral appliances and surgery provide alternatives in select populations but are variably effective. Hypoglossal nerve stimulation can effectively treat obstructive sleep apnea. Targeted hypoglossal nerve stimulation (THN) is simpler than incumbent technology with no sensor and an easier, proximal electrode implantation. The third clinical study of THN, THN3, was the first randomized, controlled trial of hypoglossal nerve stimulation to demonstrate significant improvement of sleep disordered breathing in OSA. The present investigation reports the design of a novel trial of targeted stimulation to provide additional Level 1 evidence in moderate to severe obstructive apnea. OSPREY is a randomized, parallel-arm, 13-month trial wherein all subjects are implanted, 2/3 are activated at Month 1 ("Treatment") and 1/3 are activated at Month 7 ("Control"). The primary endpoint is the difference in apnea-hypopnea index response rates between Treatment and Control groups at Month 7. Secondary endpoints include quality of life and oximetry metrics. OSPREY follows an adaptive "Goldilocks" design which optimizes the number of subjects with the need for high-confidence results. A maximum of 150 subjects is allowed, at which study power of >95% is predicted. Interim analyses begin once 50 patients are randomized and recur after each 20 additional randomizations to detect early success or futility. OSPREY is a unique, efficient trial that should provide high-confidence confirmation of the safety and efficacy of targeted hypoglossal nerve stimulation for moderate to severe obstructive sleep apnea.

Beyond VOTE: The New Frontier of Drug-Induced Sleep Endoscopy.

Alternatives to positive airway pressure therapy, including surgery, represent an important area of research. Specifically, predictors of response to surgical therapy remain underdeveloped. Drug-induced sleep endoscopy (DISE) holds promise as a diagnostic tool to identify patient-specific causes of airway collapse. Herein, we present a novel, standardized approach which combines anatomic and physiologic measurements during DISE. Our DISE platform measures airflow, airway compliance, airway collapsibility, and structural drivers of collapse. Taken together, these inputs provide a comprehensive framework to further inform the surgeon in providing personalized care of the patient with obstructive sleep apnea.

Association of sleep apnoea risk and aortic enlargement in Marfan syndrome.

BACKGROUND: Marfan syndrome (MFS) is a connective tissue disorder characterised by complex aortic pathology and a high prevalence of obstructive sleep apnoea (OSA). OSA produces intrathoracic transmural stresses that may accelerate aortic injury. The current study was designed to examine the associations between OSA risk and markers of aortic enlargement in MFS. METHOD: Consecutive patients with MFS were recruited at Johns Hopkins if they completed a STOP-BANG survey. Composite survey scores were categorised into those with low OSA risk (STOP-BANG <3) and high OSA risk (STOP-BANG ≥3). Participants' aortic data were collated to ascertain aortic root diameter, dilatation and prior aortic root replacement. Regression analyses were used to examine associations between OSA risk strata and these aortic parameters. RESULTS: Of the 89 participants studied, 28% had a high OSA risk and 32% had aortic grafts. Persons with high OSA risk had greater aortic root diameter (mm) (ß=4.13, SE=1.81, p=0.027) and aortic root dilatation (ß=2.80, SE=1.34, p=0.046) compared with those with low OSA risk . In addition, the odds of prior aortic root replacement was three times greater in those with high OSA risk compared with those with low OSA risk. CONCLUSION: In MFS, high OSA risk is associated with aortic enlargement and a threefold increased risk of having had prior aortic root replacement. These findings invite further exploration of the relationship between OSA and aortic disease in MFS, and studies to clarify whether targeted interventions for OSA might mitigate aortic disease progression in MFS. REGISTRATION NUMBER: IRB00157483.

Influence of apnea vs hypopnea predominance in predicting mean therapeutic positive airway pressures among patients with obstructive sleep apnea.

STUDY OBJECTIVES: Lower therapeutic positive airway pressure (PAP) levels are associated with improved response to non-PAP therapies in the treatment of obstructive sleep apnea. The aim of this study was to evaluate the prevailing notion that patients with apnea-predominant obstructive sleep apnea require higher therapeutic PAP levels compared to patients with hypopnea-predominant obstructive sleep apnea. METHODS: An institutional review board-approved retrospective review was performed using strict inclusion criteria: presence of type I or III sleep study, apnea-hypopnea index > 10 events/h, and adherence to auto-adjusting continuous positive airway pressure. Patients were stratified by apnea (> 50% apneas) or hypopnea (≤ 50% apneas) predominance, and PAP data were compared. Statistical analyses were performed using Student's t test and linear regression modeling. RESULTS: Between January 1, 2018 and January 1, 2020, 500 patients met inclusion criteria. Two hundred twenty-one (44.1%) patients were apnea-predominant and 279 (55.8%) were hypopnea-predominant. Apnea-predominant patients had a slightly greater mean PAP (9.01 vs 8.36, P = .002) than hypopnea-predominant patients. Univariable and multivariable linear regression of 7 variables (obstructive apnea percentage, age, sex, body mass index, apnea-hypopnea index, O2 nadir, mask type) showed obstructive apnea percentage was the weakest predictor of therapeutic PAP levels. CONCLUSIONS: Apnea-predominant individuals demonstrated a clinically insignificant difference in PAP level compared to hypopnea-predominant individuals; moreover, obstructive apnea percentage was not a strong predictor of therapeutic PAP levels. Of the modeled variables, the strongest predictor of PAP level was apnea-hypopnea index. Further studies are needed to explore these relationships as well as additional variables that may contribute to predicting therapeutic PAP levels. CITATION: Yu JL, Liu Y, Tangutur A, et al. Influence of apnea vs hypopnea predominance in predicting mean therapeutic positive airway pressures among patients with obstructive sleep apnea. J Clin Sleep Med. 2021;17(11):2171-2178.

Ansa cervicalis stimulation increases pharyngeal patency in patients with obstructive sleep apnea.

Hypoglossal nerve stimulation (HNS) is an alternative treatment option for obstructive sleep apnea (OSA) that reduces pharyngeal collapsibility, but HNS nonresponders often demonstrate continued retropalatal and lateral pharyngeal wall collapse. Recent evidence suggests that caudal pharyngeal traction with sternothyroid muscle contraction via ansa cervicalis stimulation (ACS) can also stabilize the pharynx, but the underlying mechanisms have not been elucidated. Our objective was to evaluate the effect of ACS on pharyngeal patency during expiration when the airway is most hypotonic. Eight participants with OSA underwent sustained ultrasound-guided fine-wire stimulation of the medial branch of the right hypoglossal nerve with and without transient stimulation of the branch of the ansa cervicalis nerve plexus innervating the right sternothyroid muscle during drug-induced sleep endoscopy. Airway cross-sectional area and expiratory airflow (V̇e) were measured from endoscopy video with ImageJ and pneumotachometry, respectively. ACS significantly increased retropalatal cross-sectional area (CSARP) to 211% [159-263] of unstimulated CSARP (P < 0.05). Adding ACS to HNS increased CSARP from baseline by 341% [244-439] (P < 0.05), a 180% [133-227] increase over isolated HNS (P < 0.05). ACS increased V̇e from baseline by 177% [138-217] P < 0.05). Adding ACS to HNS increased V̇e by 254% [207-301], reflecting decreases in pharyngeal collapsibility. Combining ACS with HNS increased retropalatal cross-sectional area and increased expiratory airflow, suggesting decreases in pharyngeal collapsibility. Our findings suggest that ACS exerts caudal traction on the upper airway through sternothyroid muscle contraction and that it may augment HNS efficacy in patients with OSA.NEW & NOTEWORTHY Ansa cervicalis stimulation (ACS) is a recently proposed neurostimulation mechanism for generating caudal pharyngeal traction that may benefit patients with obstructive sleep apnea. Here, we document endoscopic findings with ACS during drug-induced sleep endoscopy and additionally detail the effects of ACS on expiratory airflow, when the pharynx is known to be most hypotonic.

Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes.

BACKGROUND: The remede 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 remede 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.

Transvenous phrenic nerve stimulation improves central sleep apnea, sleep quality, and quality of life regardless of prior positive airway pressure treatment.

STUDY OBJECTIVE: Positive airway pressure (PAP) therapy for central sleep apnea (CSA) is often poorly tolerated, ineffective, or contraindicated. Transvenous phrenic nerve stimulation (TPNS) offers an alternative, although its impact on previously PAP-treated patients with CSA has not been examined. METHODS: TPNS responses among PAP-naïve and prior PAP-treated patients from the remede® System Pivotal Trial were assessed. Of 151, 56 (37%) used PAP therapy before enrolling in the trial. Patients were implanted with a TPNS device and randomized to either active or deferred (control) therapy for 6 months before therapy activation. Apnea-hypopnea index (AHI) and patient-reported outcomes (PRO) were assessed at baseline, and 6 and 12 months following active therapy. RESULTS: Patients had moderate-severe CSA at baseline, which was of greater severity and more symptomatic in the PAP-treated vs. PAP-naïve group (median AHI 52/h vs. 38, central apnea index (CAI) 32/h vs. 18, Epworth Sleepiness Scale 13 vs. 10, fatigue severity scale 5.2 vs. 4.5). Twelve months of TPNS decreased AHI to <20/h and CAI to ≤2/h. Both groups showed reductions in daytime sleepiness and fatigue, improved well-being by patient global assessment, and high therapeutic acceptance with 98% and 94% of PAP-treated and PAP-naïve patients indicating they would undergo the implant again. Stimulation produced discomfort in approximately one-third of patients, yet <5% of prior PAP-treated participants discontinued therapy. CONCLUSION: Polysomnographic and clinical responses to TPNS were comparable in PAP-naïve and prior PAP-treated CSA patients. TPNS is a viable therapy across a broad spectrum of CSA patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01816776; March 22, 2013.