Validity of Empatica E4 Wristband for Detection of Autonomic Dysfunction Compared to Established Laboratory Testing

<b>Background:</b> Heart rate variability (HRV) is a well-established marker of autonomic nervous system (ANS) activity. It is also an important tool for investigating cardiovascular and neurological health. Changes in HRV have been associated with epilepsy and sudden unexpected death in epilepsy (SUDEP), conditions in which autonomic dysregulation is believed to play a significant role. HRV is traditionally measured using electrocardiography (ECG) under standardized laboratory conditions. Recently, however, wearable devices such as the Empatica E4 wristband have emerged as promising tools for continuous, noninvasive HRV monitoring in real-life, ambulatory, and clinical settings where laboratory infrastructure may be lacking. <b>Methods:</b> We evaluated the validity and clinical utility of the Empatica E4 wristband in two cohorts. In the first cohort of healthy controls (n = 29), we compared HRV measures obtained with the E4 against those obtained with a gold-standard laboratory ECG device under seated rest and metronomic breathing conditions. In persons with epilepsy (PWE, n = 42), we assessed HRV across wake and sleep states, as well as during exposure to sodium channel blockers. This was done to determine whether the device could detect physiologically and clinically meaningful changes in autonomic nervous system (ANS) function. <b>Results:</b> In healthy participants, the Empatica E4 provided heart rate (HR), root mean square of successive R-R intervals (RMSSD), and standard deviation of all interbeat intervals (SDNN) values that were strongly correlated with laboratory measurements. Both devices detected the expected increase in RMSSD during metronomic breathing; however, the E4 consistently reported higher absolute values than the ECG. In patients with epilepsy (PWE), the E4 reliably captured parasympathetic activation during sleep and detected a significant reduction in heart rate variability (HRV) in patients taking sodium channel blockers, demonstrating its sensitivity to clinically relevant autonomic changes. <b>Conclusions:</b> The Empatica E4 wristband is valid for measuring HRV in research and clinical contexts. It can detect modulations of ANS activity that are physiologically meaningful. While HRV metrics were robust, other signals, such as electrodermal activity and temperature, were less reliable. These results highlight the potential of wearable devices as practical alternatives to laboratory-based autonomic testing, especially in emergency and resource-limited settings, and emphasize their importance in epilepsy care risk assessment.