Estimation of adaptive ventilation success and failure using polysomnogram and outpatient therapy biomarkers

Abstract

Adaptive servo-ventilation (ASV) devices provide anticyclic pressure support for the treatment of central and/or complex sleep apnea, including heart failure patients. Variability in responses in the clinic and negative clinical trials motivated assessment of standard and novel signal biomarkers for ASV efficacy. Multiple clinical databases were queried to assess potential signal biomarkers of ASV effectiveness, including the following: (1) attended laboratory adaptive ventilation titrations: 108, of which 66 had mainstream ETCO2 measurements; (2) AirView data in 98 participants, (3) complete data, from diagnostic polysomnogram (PSG) through review and prospective analysis of on-therapy data using SleepyHead freeware in 44 participants; and (4) hemodynamic data in the form of beat-to-beat blood pressure during ASV titration, using a Finometer in five participants. Signal biomarkers of reduced ASV efficacy were noted as follows: (1) an arousal index which markedly exceeded the respiratory event index during positive pressure titration; (2) persistent pressure cycling during long-term ASV therapy, visible in online review systems or reviewing data using freeware; (3) the ASV-associated pressure cycling induced arousals, sleep fragmentation, and blood pressure surges; and (4) elevated ratios of 95th percentile to median tidal volume, minute ventilation, and respiratory rate were associated with pressure cycling. High intraclass coefficients (>0.8) for machine apnea-hypopnea index and other extractable metrics were consistent with stability of patterns over multiple nights of use. Global clinical outcomes correlated negatively with pressure cycling. Potential polysomnographic- and device-related signal biomarkers of ASV efficacy are described and may allow improved estimation of therapeutic effectiveness of adaptive ventilation.