Heart rate variability analysis in controls and epilepsy patients with or without receiving treatment: a clinical review and meta-analysis

The malfunctioning of cardiac autonomic control in epileptic patients develops ventricular tachyarrhythmia and causes sudden unexpected death in epilepsy patients (SUDEP). Various clinical studies investigated the effect of epilepsy on cardiac autonomic control by performing heart rate variability (HRV) analysis; however, results are unclear regarding whether sympathetic, parasympathetic, or both branches of the autonomic nervous system (ANS) are affected in epilepsy and also the impact of anticonvulsant treatment on the ANS. This study follows the systematic protocols to investigate epilepsy and its anticonvulsant treatment on cardiac autonomic control by using linear and nonlinear HRV analysis measures. The electronic databases of PubMed, Embase, and Cochrane Library were used for the collection of studies. Initially, 1475 articles were identified whereas after 2-staged exclusion criteria, 33 studies were selected for execution of the review process and meta-analysis. For meta-analysis, four comparisons were performed (epilepsy patients): (1) controls (healthy subject with no history of epilepsy) versus untreated patients; (2) treated (patients under treatment that have a seizure) versus untreated patients; (3) controls versus treated patients; and (4) refractory versus well-controlled (epilepsy patients that were seizure-free for last 1 year). For treated and untreated patients, there was no significant difference whereas well-controlled patients presented higher values as compared to refractory patients. Meta-analysis was performed for the time-domain, frequency-domain, and nonlinear parameters. Untreated patients in comparison with controls presented significantly lower HF (high-frequency) and LF (low-frequency) values. These LF (g = − 0.9; 95% CI − 1.48 to − 0.37) and HF (g = − 0.69; 95% confidence interval (CI) − 1.24 to − 0.16) values were affirming suppressed both, vagal and sympathetic activity, respectively. Additionally, LF and HF value was increased in most of the studies indicating suppressed vagal tone, while for some studies, their value decreased to indicate suppressed sympathetic activity. No significant difference was observed for the remaining comparisons. Results affirmed the hypothesis that suppressed sympathetic activity affects sympathovagal balance and leads to SUDEP, as the LF value was significantly lower for patients as compared to healthy subjects. The overall effect size and statistical results for LF and HF were significant, showing the research and clinical significance of our study.