Association between respiration-synchronized hypoglossal nerve stimulation and changes in sleep apnea-specific hypoxic burden in patients with obstructive sleep apnea

Unilateral, respiration-synchronized hypoglossal nerve stimulation (HGNS) has become a widely used and scientifically validated innovative treatment option for selected moderate-to-severe obstructive sleep apnea (OSA) patients [1, 2]. The apnea-hypopnea index (AHI), the primary metric for the diagnosis and management of OSA, fails to capture key aspects of OSA-related hypoxemia, including frequency, duration, and depth of the ventilatory disturbance and blood gas changes [3, 4]. The sleep apnea-specific hypoxic burden (SASHB) is a novel metric to assess OSA severity, characterizing respiratory event-related depth, duration, and frequency of oxygen desaturations [4]. SASHB is defined as the total area under the oxygen desaturation curve associated with respiratory events [4]. Observational epidemiological studies showed that an SASHB ≥60%min/h may predict increased OSA-related cardiovascular risk [4]. This proof-of-concept study evaluated the association between respiration-synchronized HGNS and changes in SASHB at 1-year post-implantation in patients with moderate-to-severe OSA. Consecutive patients with moderate-to-severe OSA (15/h ≤ AHI ≤ 65/h) implanted with a respiration-synchronized HGNS device (Inspire IV; Inspire Medical Systems Inc., Golden Valley, MN, USA) between 2019 and 2024, and with available type I polysomnography data at baseline and 1-year post-implantation were included. Patient selection, HGNS implantation, and post-implant care were conducted in accordance with previously published protocols [1, 5, 6]. Local ethics committee approval (B3002024000047) and written informed consent from all participants were obtained. Respiratory events were scored according to American Academy of Sleep Medicine 2014 criteria (hypopnea defined as ≥3% decrease in oxygen saturation or arousal) [7]. Surgical success was defined by Sher15 criteria (AHI < 15 events/h and ≥50% reduction from baseline). SASHB was calculated from the raw polysomnography data according to Azarbarzin et al. [4]. Objective therapy usage data were obtained from the implantable pulse generator records at 1-year post-implantation. Statistical analysis was performed using SPSS v27.0 (SPSS Inc., Chicago, IL, USA). Normally distributed data are reported as mean ± standard deviation; non-normally distributed data as median [Quartile 1–Quartile 3]. Changes from baseline to 1-year follow-up were analyzed using a paired Wilcoxon signed-rank test. Adjusted analysis including sex, age, and body mass index (BMI) was performed by using linear mixed effect models with subject as random effect. Spearman’s rank-order correlations were conducted to assess the relationship between AHI, oxygen desaturation index (ODI), percentage of sleep time with an oxygen saturation below 90% (T90), and SASHB at baseline, follow-up, and for their respective percent changes. Linear regression analysis was performed to assess the relationship between delta BMI and delta SASHB. A p value of