Analysis of heart rate variability and risk factors for SUDEP in patients with drug-resistant epilepsy.

Background: Cardiac problems have been suggested as causes of sudden unexpected death in epilepsy (SUDEP). Our aim was to investigate possible associations of cardiac autonomic functions based on heart rate variability (HRV) parameters with risk factors of SUDEP in patients with drug-resistant epilepsy.

Methods: Forty-seven patients with drug-resistant seizures and 45 healthy control subjects were enrolled in the study. Interictal time domain parameters of HRV were evaluated with 24-hour Holter recordings. Potential SUDEP risk in patients with epilepsy was estimated using an inventory of seven validated SUDEP risk factors (The SUDEP-7 inventory).

Results: When compared with the healthy controls, all time domain measures (SDNN-24, SDNN-index, SDANN-index, RMSSD and pNN50) were significantly suppressed in the patient group. Scores of the SUDEP-7 inventory ranged from 1 to 9 with a median 4 out of a maximum possible risk score of 10. Maximum heart rate value in 24-hour Holter recordings and epilepsy duration were correlated with the SUDEP-7 scores (r=0.3, p=0.03). We found no significant association with HRV measures and SUDEP-7 risk factors. One patient diagnosed with Dravet syndrome died of SUDEP, which was autopsy confirmed; his SUDEP-7 inventory score was 7, HRV measures were significantly diminished, and his maximum heart rate (HR) was 208beats/min (maximum HR is between 104 and 188beats/min in normal subjects).

Conclusion: Patients with drug-resistant epilepsy present with significantly lower HRV measures, which may increase the risk for sudden cardiac death. Increased heart rate and diminished HRV measures may constitute one of the possible mechanisms underlying SUDEP and should be diagnosed in patients with epilepsy.