Assessment of Autonomic Nervous System Function in Patients with Chronic Fatigue Syndrome and Post-COVID-19 Syndrome Presenting with Recurrent Syncope

Background/Objectives: Chronic fatigue syndrome and post-COVID-19 syndrome are associated with dysfunction of the autonomic nervous system, which may manifest as syncope and orthostatic intolerance. This study aimed to compare autonomic nervous system function in patients with chronic fatigue syndrome of unknown etiology and those with chronic fatigue syndrome secondary to post-COVID-19 syndrome using multiple diagnostic modalities, and to assess the prevalence and characteristics of syncope in these populations. Methods: This cross-sectional study included 440 patients examined at the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases "Dedinje". Patients were divided into three groups: chronic fatigue syndrome of unknown etiology (Group 1, n = 210), chronic fatigue syndrome secondary to post-COVID-19 syndrome (Group 2, n = 137), and healthy controls (Group 3, n = 91). Diagnostic modalities included cardiovascular reflex tests, the head-up tilt test, beat-to-beat analysis, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses were performed using analysis of variance, Tukey's honestly significant difference test, and the Mann-Whitney U test. Results: Both chronic fatigue syndrome groups demonstrated significant autonomic nervous system dysfunction compared to healthy controls (p < 0.05), including reduced baroreceptor sensitivity and impaired heart rate variability parameters. Syncope prevalence was high in both chronic fatigue syndrome groups, with extreme blood pressure variability observed in 45-47% of patients during the head-up tilt test. Patients with post-COVID-19 chronic fatigue syndrome exhibited greater blood pressure increases during the head-up tilt test than those with chronic fatigue syndrome of unknown etiology (p < 0.05). Conclusions: Patients with chronic fatigue syndrome, irrespective of etiology, exhibit significant autonomic nervous system dysfunction and a high prevalence of syncope. Post-COVID-19 chronic fatigue syndrome demonstrates distinct hemodynamic patterns, suggesting unique pathophysiological mechanisms that warrant further investigation.