Wearable Device Photoplethysmography is a Viable Tool to Longitudinally Monitor Vasoconstriction Biomarkers for Predicting Vaso-occlusive Crisis in Sickle Cell Disease (Preprint)

BACKGROUND Entrapment of sickled red blood cells in the microvasculature leads to sudden painful vaso-occlusive crises (VOC) in sickle cell disease (SCD). This is potentially triggered by autonomic nervous system mediated vasoconstriction in peripheral vasculature and resultant decrease in microvascular blood flow. Indeed, vasoconstriction biomarkers derived from a single night of laboratory-based fingertip photoplethysmography (PPG) recording were predictive of higher frequency of future VOC in SCD. Non-invasive, remote and longitudinal monitoring of autonomic vasoreactivity will facilitate development of predictive biomarkers of imminent VOC. OBJECTIVE To assess the feasibility and performance of wearable wristband device to longitudinally monitor nocturnal peripheral autonomic vasoreactivity and to cross-validate the vasoconstriction parameters across the “gold-standard” finger sensor. METHODS 11 subjects with SCD and 5 healthy controls were recruited to wear a wristband device (Biostrap) with PPG sensor on a nightly basis. For cross-validation studies, 3 subjects wore both the wristband and a sleep monitoring device (AliceNightOne) with finger PPG sensor. We quantified autonomic vasoreactivity by processing PPG signals and deriving vasoconstriction parameters - magnitude of vasoconstriction (Mvasoc) and Coefficient of Variation (PPGampCV). We performed correlation analysis of the vasoconstriction parameters within each device to investigate if Mvasoc and PPGamp CV can be surrogate markers of vasoconstriction and then cross-validated the PPGampCV across the wristband and finger PPG devices. RESULTS A total of 115 nocturnal PPG recordings were made with wristband device (1-19 nights/subject; SCD=70, controls=45). A total of 9 nocturnal recordings (3 nights/subject) were made with both wristband and finger sensor devices. Longitudinal continuous PPG recordings were feasible with wearable devices with subjects reporting ease of use. There was significant within night and night-to-night variability in vasoconstriction parameters suggesting dynamic changes in autonomic vasoreactivity. Mvasoc and PPGampCV significantly correlated within devices - the maximum overnight correlation was 0.82 (P<.001) for finger sensor and 0.69 (P <.001) for wristband sensor, suggesting that PPGampCV can serve as a surrogate for Mvasoc. Cross-validation analysis of PPGampCV across wristband and fingertip sensors showed statistically significant correlation across all nights (overnight correlation coefficient ranging from 0.24-0.7) with some nightly segments of PPGampCV showing near perfect correlation between devices. CONCLUSIONS Wearable wristband devices are feasible tools for collection of continuous PPG measurements and vasoconstriction parameters, which serve as objective markers of autonomic vasoreactivity in subjects with and without SCD. We have optimized the methods of quantifying vasoconstriction from wearable device PPG signals, while minimizing effects of artefacts and cross-validated them with standardized sensors. These findings enable large scale, real-time monitoring of autonomic vasoreactivity along with pain outcomes for the development of vasoconstriction parameters as a biomarker of imminent VOC in SCD. This biomarker has potential to impact not only SCD but also other diseases involving autonomic vascular dysregulation.