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Endotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

RATIONALE
Approximately a 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. 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 trial were included. Raw baseline polysomnographic data from 91/126 patients were available for analysis. Traits-loop gain, arousal threshold, collapsibility, muscle compensation-were calculated from the baseline polysomnography data according to Sands et al. (AJRCCM 2018, SLEEP 2018). Logistic regression assessed AHI-adjusted associations between HGNS response (>50% reduction in AHI to <10/h at 1 year) and OSA traits.


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 [Q1-Q3]); N=53/91 were responders. In adjusted analysis, a favorable response to therapy was independently associated with higher arousal threshold (OR [95%CI]: 6.76 [2.44-23.3], P=0.001), greater compensation (OR: 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 prior to adjusted analysis. Predicted responders had a ~4-fold lower treatment AHI versus predicted non-responders (4.9 [2.7-8.5] vs 20.7 [10.9-29.7], P<0.0001; median [Q1-Q3]); 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.