Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition with no reliable diagnostic biomarkers. Studies have shown evidence of autonomic dysfunction in patients with ME/CFS, but results have been equivocal. Heart rate (HR) parameters can reflect changes in autonomic function in healthy individuals; however, this has not been thoroughly evaluated in ME/CFS. METHODS: A systematic database search for case-control literature was performed. Meta-analysis was performed to determine differences in HR parameters between ME/CFS patients and controls. RESULTS: Sixty-four articles were included in the systematic review. HR parameters assessed in ME/CFS patients and controls were grouped into ten categories: resting HR (RHR), maximal HR (HR(max)), HR during submaximal exercise, HR response to head-up tilt testing (HR(tilt)), resting HR variability (HRV(rest)), HR variability during head-up tilt testing (HRV(tilt)), orthostatic HR response (HR(OR)), HR during mental task(s) (HR(mentaltask)), daily average HR (HR(dailyaverage)), and HR recovery (HRR) Meta-analysis revealed RHR (MD ± 95% CI = 4.14 ± 1.38, P < .001), HR(tilt) (SMD ± 95% CI = 0.92 ± 0.24, P < .001), HR(OR) (0.50 ± 0.27, P < .001), and the ratio of low frequency power to high frequency power of HRV(rest) (0.39 ± 0.22, P < .001) were higher in ME/CFS patients compared to controls, while HR(max) (MD ± 95% CI = –13.81 ± 4.15, P < .001), HR at anaerobic threshold (SMD ± 95% CI = –0.44 ± 0.30, P = 0.005) and the high frequency portion of HRV(rest) (–0.34 ± 0.22, P = .002) were lower in ME/CFS patients. CONCLUSIONS: The differences in HR parameters identified by the meta-analysis indicate that ME/CFS patients have altered autonomic cardiac regulation when compared to healthy controls. These alterations in HR parameters may be symptomatic of the condition.