Abstracts

Rationale: Autopsy examinations of epilepsy patients reveal myopathologic lesions that in other contexts have been associated with cardiotoxic effects of excess catecholamines, which may implicate a cardiac component of risk for sudden unexpected death in epilepsy (SUDEP). T-wave alternans is an established marker of risk for sudden death in patients with cardiovascular disease. We determined the effect of vagus nerve stimulation (VNS) on cardiac electrical instability as assessed by T-wave alternans (TWA) in patients with drug-resistant epilepsy.Methods: Patients from the E-36 clinical trial on the AspireSR ® VNS Therapy System® (NCT01325623) were monitored with ambulatory ECGs approximately two weeks prior to de novo VNS system implantation. Exclusion criteria included history of clinically meaningful cardiovascular arrhythmias, and medication with beta-adrenergic antagonists and other cardioactive agents prescribed for a cardiac or autonomic disorder. After implant and recovery, patients were titrated to an output current to at least 0.5 mA over a 2-4 week period, at which time they began a 3- to 5-day epilepsy monitoring unit (EMU) stay with standard EMU monitoring where concurrent EEG/ECG were collected. TWA level was assessed by the Modified Moving Average (MMA) method.Results: At baseline, 26 (84%) of 31 patients evidenced TWA levels ≥47 μV, the criterion for abnormality. TWA level of the group was 72±3.9 μV (mean±SEM), which exceeds the 60-μV cutpoint for severely abnormal TWA. Patients entered the EMU a median of 3 weeks after implant of the VNS Therapy system implant and achieving a median output current of 0.75 mA. As compared with the baseline pre-implant values, TWA levels in the EMU decreased by 43% to 41±2.3 μV (p<0.001); and only 7 (23%) patients had TWA ≥47. Heart rate variability parameters were unchanged. Figure: In a representative patient, TWA decreased from 67 (pre-VNS) to 21 μV (post-VNS) (upper panel); graph of significant decrease in TWA with VNS (lower panel). Templates of QRS-aligned, superimposed beats revealed a separation in morphology of A and B beats, reflecting an ABAB pattern, which is the hallmark of TWA and its electrophysiologic basis for estimating risk for arrhythmic death.Conclusions: VNS reduces cardiac electrical instability assessed by quantitative TWA in patients with drug-resistant epilepsy. These findings suggest vulnerability to cardiac arrhythmic events in this population and VNS as a novel approach to risk reduction.