Objective:We aimed to test whether patients who died from sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation.Methods:We conducted a retrospective, observational, case-control study of a group of patients who died from SUDEP and controls who were matched with the patients for epilepsy type, drug resistance, sex, age at electroencephalogram recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and heart rate variability (HRV) at rest, during and after hyperventilation performed during the patient’s last electroencephalogram recording before SUDEP. In each group, changes over time in HRV indexes were analyzed using linear mixed models.Results:Twenty patients were included in each group. In the control group, the HR increased and the RMSSD decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 min after its end discriminated well between SUDEP patients and control patients (AUC: 0.870; sensitivity: 85%; specificity: 75%).Conclusion:Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in heart rate upon hyperventilation (dHRh) might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures.

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