Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial

Abstract

Objective: Reports of cardiac arrhythmias and cardiac pathology at postmortem examination of patients with epilepsy suggest a possible cardiac component of risk for sudden unexpected death in epilepsy (SUDEP). T-wave alternans (TWA) is an established marker of cardiac electrical instability and risk for sudden death in patients with cardiovascular disease. We determined the TWA level before vagus nerve stimulation (VNS) system implantation and subsequently the effect of VNS on TWA in patients with drug-resistant epilepsy.

Methods: Patients (n=28) from the Seizure Detection and Automatic Magnet Mode Performance Study (E-36), a clinical trial of the AspireSR® VNS Therapy System® (NCT01325623), were monitored with ambulatory electrocardiograms (ECGs) ~2weeks before de novo VNS system implantation and following 2- to 4-week VNS titration during a protocol-specified 3- to 5-day epilepsy monitoring unit stay with concurrent EEG/ECG recordings. The TWA level was assessed interictally by the Modified Moving Average (MMA) method.

Results: At preimplantation baseline, TWA was elevated above the 47-μV abnormality cutpoint in 23 (82%) patients with drug-resistant epilepsy. In 16 (70%) patients, TWA level was reduced during VNS treatment to <47μV, thereby converting positive TWA test results to negative. Peak TWA level in all 28 patients improved (group mean, 43%, from 72±4.3 to 41±2.3μV; p<0.0001). Vagus nerve stimulation was not associated with reduced heart rate (77±1.4 to 75±1.4beats/min; p=0.18). Heart rate variability was unchanged.

Significance: These findings suggest significant interictal cardiac electrical instability in this population of patients with drug-resistant epilepsy and suggest that VNS may be a novel approach to reducing risk.

Keywords: Biomarker; Epilepsy; Risk reduction; Sudden unexpected death in epilepsy; T-wave alternans.