Prediction of Vasovagal Syncope using Artificial Intelligence-enabled Smartwatch Photoplethysmography-derived Heart Rate Variability

Abstract Background Vasovagal syncope (VVS) can cause injury and impaired quality of life, and effective prevention requires timely warning before loss of consciousness. Objectives To evaluate whether smartwatch photoplethysmography (PPG)-derived heart rate variability (HRV) can predict VVS before symptom onset, and to identify an optimal observation window and lead time. Methods We prospectively enrolled 132 patients with suspected neurally mediated syncope who underwent head-up tilt (HUT) testing while wearing a wrist-worn Samsung Galaxy Watch 6 for continuous multiwavelength PPG acquisition (25 Hz). The HRV features (n=107) were extracted. An Extra Trees classifier (600 trees) was trained using an 80/20 subject-level split and evaluated on a hold-out test set. Model performance was assessed using the AUROC and threshold metrics, including specificity, at a fixed sensitivity of 0.90. Results Sixty-three participants were HUT-positive and 69 were HUT-negative. The 5-min presyncope window achieved the highest discrimination (AUROC, 0.91; 95% CI 0.77–1.00). At 90% sensitivity, specificity was 0.64 (95% CI 0.40–0.85). Using a fixed 5-min window, early prediction remained robust at a 5-min lead time (AUROC 0.91; 95% CI 0.76–1.00; accuracy 84.6%; 95% CI 0.65–0.92). The most informative predictors included nonlinear complexity metrics (approximate entropy and composite multiscale entropy) and autonomic balance indices (normalised low-frequency, log-transformed high-frequency, and the cardiac vagal index). Conclusion Artificial intelligence-enabled analysis of smartwatch PPG–derived HRV can prospectively predict VVS during HUT using a short 5-min observation window while maintaining clinically meaningful performance at a 5-min lead time, supporting the feasibility of wearable, real-time warning systems.