Objective: The purpose of this investigation was to examine heart rate variability (HRV), interbeat interval (IBI), and their interrelationship in healthy subjects, bradycardic HCN4 mutation carriers, and patients with anorexia nervosa (AN). We hypothesized that bradycardia in patients with AN is caused by neural mechanisms. Therefore, we assumed that a saturation effect of the HRV/IBI relationship in consequence of sustained parasympathetic control of the sinus node is exclusively detectable in patients with AN. Method: Patients with AN between the ages of 12 and 16 years admitted to our hospital due to malnutrition were grouped (N = 20). A matched-pair group with healthy children and adolescents was created. Groups were matched for age and gender. We performed 24-hour Holter electrocardiography (ECG) in controls and patients. Specifically, all patients underwent two 24-hour Holter ECGs (admission; refeeding treatment). Additionally, IBI's were recorded during night-time in HCN4 mutation carriers (N = 4). HRV parameters were analyzed in 5-minute sequences during night-time and plotted against mean corresponding IBI length. HRV, IBI, and their interrelationship were examined by calculating saturation indices, Spearman's rank correlation analyses, Mann-Whitney U-and Wilcoxon signed-rank tests. Results:The relationship between IBI and HRV showed signs of saturation in patients with AN. Signs of HRV saturation were also present in two HCN4 mutation carriers. In contrast, signs of HRV saturation were barely present in controls. Discussion:We believe that non-neural mechanisms such as HCN4 down-regulation are possible explanations for HRV saturation and the associated bradycardia in patients with AN.
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