Heart rate variability modification as a predictive factor of sudden unexpected death in epilepsy: How far are we? A systematic review and meta‐analysis

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected death in people with epilepsy, with or without evidence of an epileptic seizure. The pathophysiological mechanism underlying SUDEP appears to be partly associated with an autonomic nervous system (ANS) dysfunction. Heart rate variability (HRV) analysis is a reliable, non-invasive method for detecting fluctuations in the ANS. In this systematic review we analyzed the data available in the literature on changes in HRV parameters in patients with SUDEP. METHODS: We carried out a systematic search of the literature to identify the quantitative variations of HRV in epileptic patients with SUDEP. The following databases were used: Pubmed, Google Scholar, EMBASE, and CrossRef. A pooled analysis was carried out, and the results obtained were compared using mean difference (MD). The review was registered on the PROSPERO platform (CRD42021291586). RESULTS: Seven articles were included, with a total of 72 SUDEP cases associated with altered HRV parameters. Generally, a reduction of SDNN (standard deviation of the RR intervals) and RMSSD (root mean square differences of successive RR intervals) was reported in most SUDEP patients. According to MD, the SUDEP patients showed no differences in time and frequency domain parameters compared to controls. However, a trend toward increased low frequency and high frequency ratio (LF/HF) was observed in the SUDEP patients. CONCLUSIONS: HRV analysis is a valuable method for assessing cardiovascular risk and cardioautonomic impairment. Although a possible association between HRV variation and SUDEP has been reported, further studies are needed to assess the potential role of HRV modifications as a SUDEP biomarker.