Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 203, Issue 6, Pages 746-755Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.202006-2176OC
Keywords
arousal threshold; pathophysiology; precision medicine; sleep-disordered breathing; upper airway stimulation
Categories
Funding
- Inspire Medical Systems
- Research Foundation Flanders (FWO) [12H4520N]
- Research Foundation Flanders (FWO) in Belgium [1833517N]
- American Heart Association [15SDG25890059]
- NIH NHLBI [R01HL146697]
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Favorable responses to hypoglossal nerve stimulation therapy are associated with the pathophysiological traits causing obstructive sleep apnea, particularly a higher arousal threshold.
Rationale: Approximately one-third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy. Objectives: Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy. Methods: Baseline polysomnography data of the STAR (Stimulation Therapy for Apnea Reduction) trial were included. Raw baseline polysomnographic data from 91/126 patients were available for analysis. Traits-loop gain, arousal threshold, collapsibility, and muscle compensation-were calculated from the baseline polysomnography data according to Sands and colleagues (AJRCCM 2018, SLEEP 2018). Logistic regression assessed apnea-hypopnea index (AHI)-adjusted associations between HGNS response (>50% reduction in AHI to <10/h at 1 yr) and OSA traits. Measurements and Main Results: Overall, HGNS treatment reduced AHI from 30.7 (24.9-39.9) to 8.5 (4.0-19.5) events/h (P < 0.0001; median[quartiles 1-3]); N=53/91 were responders. In adjusted analysis, a favorable response to therapy was independently associated with higher arousal threshold (odds ratio [95% confidence interval]: 6.76 [2.44-23.3], P=0.001), greater compensation (odds ratio: 4.22 [1.70-12.55] per SD, P=0.004), and lower loop gain (in milder collapsibility, per significant interaction, P=0.003). The higher arousal threshold was evident in responders before adjusted analysis. Predicted responders had an approximately fourfold lower treatment AHI versus predicted nonresponders (4.9 [2.7-8.5] vs. 20.7 [10.9-29.7], P < 0.0001; median [quartiles 1-3]); differences remained significant after cross-validation. Conclusions: Favorable responses to HGNS therapy are associated with the pathophysiological traits causing OSA, particularly a higher arousal threshold. Along with established criteria, individuals with favorable traits could potentially be prioritized for precision HGNS therapy.
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