Heart rate variability as a potential biomarker of pediatric obstructive sleep apnea resolution

Abstract

Study objectives: Pediatric obstructive sleep apnea (OSA) affects cardiac autonomic regulation, altering heart rate variability (HRV). Although changes in classical HRV parameters occur after OSA treatment, they have not been evaluated as reporters of OSA resolution. Specific frequency bands (named BW1, BW2, and BWRes) have been recently identified in OSA. We hypothesized that changes with treatment in these spectral bands can reliably identify changes in OSA severity and reflect OSA resolution.

Methods: Four hundred and four OSA children (5-9.9 years) from the prospective Childhood Adenotonsillectomy Trial were included; 206 underwent early adenotonsillectomy (eAT), while 198 underwent watchful waiting with supportive care (WWSC). HRV changes from baseline to follow-up were computed for classical and OSA-related frequency bands. Causal mediation analysis was conducted to evaluate how treatment influences HRV through mediators such as OSA resolution and changes in disease severity. Disease resolution was initially assessed by considering only obstructive events, and was followed by adding central apneas to the analyses.

Results: Treatment, regardless of eAT or WWSC, affects HRV activity, mainly in the specific frequency band BW2 (0.028-0.074 Hz). Furthermore, only changes in BW2 were specifically attributable to all OSA resolution mediators. HRV activity in BW2 also showed statistically significant differences between resolved and non-resolved OSA.

Conclusions: OSA treatment affects HRV activity in terms of change in severity and disease resolution, especially in OSA-related BW2 frequency band. This band allowed to differentiate HRV activity between children with and without resolution, so we propose BW2 as potential biomarker of pediatric OSA resolution.

Clinical trial registration: Childhood Adenotonsillectomy Trial, NCT00560859, https://sleepdata.org/datasets/chat.

Keywords: biomarker; causal mediation analysis; frequency domain analysis; heart rate variability; obstructive sleep apnea; resolution; treatment.