Wearable Device Photoplethysmography As a Viable Tool to Longitudinally Monitor Vasoconstriction Biomarkers for Predicting Vaso-Occlusive Crisis in Sickle Cell Disease: Feasibility and Validation Study.

Background: Entrapment of sickled red blood cells in the microvasculature leads to sudden painful vaso-occlusive crises (VOCs) in sickle cell disease (SCD). This is potentially triggered by autonomic nervous system-mediated vasoconstriction in the microvasculature. Indeed, vasoconstriction biomarkers derived from a single night of laboratory-based fingertip photoplethysmography (PPG) recording were predictive of a higher frequency of future VOC in SCD. Noninvasive, remote, and longitudinal monitoring of autonomic vasoreactivity will facilitate the development of predictive biomarkers of imminent VOC. Objective: This study aimed to assess the feasibility and performance of a wearable wristband device to longitudinally monitor nocturnal peripheral autonomic vasoreactivity and to cross-validate the vasoconstriction parameters across the "gold-standard" finger sensor. Methods: A total of 12 patients with SCD and 6 healthy controls were recruited to wear a wristband device (Biostrap) with a PPG sensor on a nightly basis. For cross-validation studies, 50% (3/6) controls wore both the wristband and a sleep monitoring device (AliceNightOne) with a finger PPG sensor. We quantified autonomic vasoreactivity by processing PPG signals and deriving vasoconstriction parameters-magnitude of vasoconstriction (Mvasoc) and photoplethysmography amplitude coefficient of variation (PPGampCV). We performed a correlation analysis of the vasoconstriction parameters within each device to investigate whether Mvasoc and PPGampCV can be used as surrogate markers of vasoconstriction, and then cross-validated the PPGampCV across the wristband and finger PPG devices. Results: A total of 131 nocturnal PPG recordings were made with a wristband device (1-19 nights per participant; patients with SCD: n=79, 60%; controls: n=52, 40%). A total of 9 nocturnal recordings (3 nights per participant) were made with both wristband and finger sensor devices. Longitudinal continuous PPG recordings were feasible with the wearable device, with 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 the finger sensor and 0.69 (P<.001) for the 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 correlations on all 9 nights (overnight correlation coefficient ranging from 0.24-0.7), with some nightly segments of PPGampCV showing very strong correlation across devices. Conclusions: Wearable wristband devices are feasible tools for the collection of continuous PPG measurements and vasoconstriction parameters, which serve as objective markers of autonomic vasoreactivity in users with and without SCD. We have optimized the methods of quantifying vasoconstriction from wearable device PPG signals, 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 biomarkers imminent VOC in patients with SCD. This biomarker also has the potential to impact other diseases involving autonomic vascular dysregulation.