Chronic vagus nerve stimulation reverses heart rhythm complexity in patients with drug-resistant epilepsy: An assessment with multiscale entropy analysis.

OBJECTIVE: Vagus nerve stimulation (VNS) is an adjunctive treatment in drug-resistant epilepsy. The alterations in heart rate dynamics through VNS are not well understood. This study aimed to determine changes in heart rhythm complexity in association with VNS and to relate the findings to the outcome of VNS treatment in patients with drug-resistant epilepsy.

METHODS: We prospectively analyzed 32 patients with drug-resistant epilepsy, who underwent VNS implantation, and 32 age- and sex-matched healthy control subjects. The interictal heartbeat intervals were analyzed using the heart rhythm complexity with multiscale entropy (MSE) and traditional heart rate variability (HRV) analyses based on ambulatory 24-hour electrocardiograms (ECGs).

RESULTS: Patients had significantly decreased complexity indices (Slope 5, Area 1-5, Area 6-15, Area 6-20) on MSE analysis and decreased HRV measurements (standard deviation of the heartbeat interval (SDNN), square root of the mean of sum of squares of the differences between adjacent RR intervals (RMSSD), pNN50, very low frequency (VLF), low frequency (LF), high frequency (HF), total power (TP)) in time and frequency domain analyses. After one year of VNS treatment in patients with drug-resistant epilepsy, there was a trend in an elevated MSE profile with significant higher values between the scales 1 and 9. Vagus nerve stimulation induces a more significant increase of MSE in VNS responders than those in the nonresponders. The conventional HRV measurements did not change.

CONCLUSION: Our results suggest that heart rhythm complexity is impaired in patients with drug-resistant epilepsy, and this is at least partially reversed by VNS treatment. Furthermore, VNS-induced effects on heart rate complexity may be associated with the therapeutic response to VNS in patients with drug-resistant epilepsy.