Abstracts

Rationale: T-wave alternans (TWA), a beat-to-beat fluctuation in the amplitude and shape of the T wave in the electrocardiogram, has proven to be a noninvasive marker of risk for sudden cardiac death. Previous reports have shown that patients with generalized tonic-clonic seizures or complex partial seizures exhibit markedly elevated levels of TWA to ~70 μV at baseline (Strzelczyk et al, Epilepsia 2011:52:2112-7). This level exceeds the 47-μV criterion for life-threatening cardiac arrhythmia risk in patients with cardiovascular disease (TWA Consensus Guideline, J Am Coll Cardiol 2011;58:1309-24). Our first goal was to measure the degree of elevation of TWA in patients with drug-resistant epilepsy. Our second goal was to determine the impact of vagus nerve stimulation (VNS) on TWA and heart rate variability (HRV), an indicator of abnormal autonomic function implicated in sudden unexpected death in epilepsy (SUDEP). Methods: Ambulatory electrocardiograms of patients with VNS devices (N=9, ages 29-63, 6 men, 3 women) were analyzed for TWA using the Modified Moving Average method and for low- to high-frequency (LF/HF) ratio HRV during the interictal period. BIDMC's Committee on Clinical Investigations approved the study. Results: Mean TWA was 37±4.3 μV in lead V₁ for the 9 patients monitored following VNS implantation. Of these, 6 patients also monitored prior to VNS showed an average reduction in TWA in lead V₁ of 24 µV (from 60 ± 4.3 µV before to 35.7 ± 4.7 µV after VNS was adjusted to treatment settings, p= 0.02). There was a concomitant 18% decrease in LF/HF ratio, from 1.8±0.2 before to 1.5±0.1 after VNS activation, indicative of a shift toward increased parasympathetic tone. Conclusions: Patients with drug-refractory seizures have an elevated level of TWA, an independent marker of cardiac electrical instability. VNS reduces TWA levels to below the 47- μV cutpoint of abnormality. The corresponding decrease in LF/HF ratio suggests that enhanced parasympathetic tone may play a role, given its demonstrated capacity to suppress ventricular arrhythmias. These findings may provide further insight into a possible cardiac marker for risk of SUDEP. These findings suggest that VNS may have a cardioprotective role in addition to its benefits related to seizure control.