Association of Short-term Heart Rate Variability and Sudden Unexpected Death in Epilepsy

Abstract

<h3>Background and Objectives</h3> We compared heart rate variability (HRV) in sudden unexpected death in epilepsy (SUDEP) cases and living epilepsy controls. <h3>Methods</h3> This international, multicenter, retrospective, nested case–control study examined patients admitted for video-EEG monitoring (VEM) between January 1, 2003, and December 31, 2014, and subsequently died of SUDEP. Time domain and frequency domain components were extracted from 5-minute interictal ECG recordings during sleep and wakefulness from SUDEP cases and controls. <h3>Results</h3> We identified 31 SUDEP cases and 56 controls. Normalized low-frequency power (LFP) during wakefulness was lower in SUDEP cases (median 42.5, interquartile range [IQR] 32.6–52.6) than epilepsy controls (55.5, IQR 40.7–68.9; <i>p</i> = 0.015, critical value = 0.025). In the multivariable model, normalized LFP was lower in SUDEP cases compared to controls (contrast −11.01, 95% confidence interval [CI] −20.29 to 1.73; <i>p</i> = 0.020, critical value = 0.025). There was a negative correlation between LFP and the latency to SUDEP, where each 1% incremental reduction in normalized LFP conferred a 2.7% decrease in the latency to SUDEP (95% CI 0.95–0.995; <i>p</i> = 0.017, critical value = 0.025). Increased survival duration from VEM to SUDEP was associated with higher normalized high-frequency power (HFP; <i>p</i> = 0.002, critical value = 0.025). The survival model with normalized LFP was associated with SUDEP (<i>c</i> statistic 0.66, 95% CI 0.55–0.77), which nonsignificantly increased with the addition of normalized HFP (<i>c</i> statistic 0.70, 95% CI 0.59–0.81; <i>p</i> = 0.209). <h3>Conclusions</h3> Reduced short-term LFP, which is a validated biomarker for sudden death, was associated with SUDEP. Increased HFP was associated with longer survival and may be cardioprotective in SUDEP. HRV quantification may help stratify individual SUDEP risk. <h3>Classification of Evidence</h3> This study provides Class III evidence that in patients with epilepsy, some measures of HRV are associated with SUDEP.