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Meta-Analysis
. 2019 Oct;98(43):e17600.
doi: 10.1097/MD.0000000000017600.

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

Maximillian J Nelson  1 , Jasvir S Bahl  1 , Jonathan D Buckley  1 , Rebecca L Thomson  1   2 , Kade Davison  1
Affiliations
Meta-Analysis

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

Maximillian J Nelson et al. Medicine (Baltimore). 2019 Oct.

Abstract

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 (HRmax), HR during submaximal exercise, HR response to head-up tilt testing (HRtilt), resting HR variability (HRVrest), HR variability during head-up tilt testing (HRVtilt), orthostatic HR response (HROR), HR during mental task(s) (HRmentaltask), daily average HR (HRdailyaverage), and HR recovery (HRR) Meta-analysis revealed RHR (MD ± 95% CI = 4.14 ± 1.38, P < .001), HRtilt (SMD ± 95% CI = 0.92 ± 0.24, P < .001), HROR (0.50 ± 0.27, P < .001), and the ratio of low frequency power to high frequency power of HRVrest (0.39 ± 0.22, P < .001) were higher in ME/CFS patients compared to controls, while HRmax (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 HRVrest (-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.

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Conflict of interest statement

The authors have no sources of funding or conflicts of interest to declare.

Figures

Figure 1
Figure 1
Literature search flow chart. n number of included studies.
Figure 2
Figure 2
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on resting heart rate. Weight outside of parentheses indicates weighting within relevant subgroup analysis, weight inside parentheses indicates weighting within total resting heart rate analysis. CI = confidence interval, HR = heart rate, MD = mean difference, n number of participants, ME/CFS = myalgic encephalomyelitis/ chronic fatigue syndrome.
Figure 3
Figure 3
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on maximal heart rate. Weight outside of parentheses indicates weighting within relevant subgroup analysis, weight inside parentheses indicates weighting within total maximal heart rate analysis. CI = confidence interval, HR = heart rate, HRmax = maximal heart rate, MD = mean difference, ME/CFS = myalgic encephalomyelitis/chronic fatigue syndrome, n = number of participants.
Figure 4
Figure 4
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on submaximal exercise heart rate. CI = confidence interval, HR = heart rate, ME/CFS = myalgic encephalomyelitis/chronic fatigue syndrome, n = number of participants, SMD = standardized mean difference.
Figure 5
Figure 5
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on heart rate in response to head-up tilt testing. Weight outside of parentheses indicates weighting within relevant subgroup analysis, weight inside parentheses indicates weighting within total heart rate during HUTT analysis. CI = confidence interval, HR = heart rate, ME/CFS = myalgic encephalomyelitis/chronic fatigue syndrome, n = number of participants, SMD = standardized mean difference.
Figure 6
Figure 6
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on orthostatic heart rate response. Weight outside of parentheses indicates weighting within relevant subgroup analysis, weight inside parentheses indicates weighting within total orthostatic response heart rate analysis. CI = confidence interval, HR = heart rate, ME/CFS = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, n = number, SMD = standardized mean difference.
Figure 7
Figure 7
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on resting heart rate variability. CI = confidence interval, LF/HF = low frequency power/high frequency power, ME/CFS = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, n = number of participants, RMSSD = root-mean-square difference of successive normal R-R intervals from time-domain analysis, SMD = standardized mean difference.
Figure 8
Figure 8
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on heart rate variability during head-up tilt testing. CI = confidence interval, HFP = high frequency power, LF/HF = low frequency/high frequency, LFP = Low frequency power, ME/CFS = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, n = number of participants, SMD = standardized mean difference.
Figure 9
Figure 9
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on heart rate response to mental task. Weight outside of parentheses indicates weighting within relevant subgroup analysis, weight inside parentheses indicates weighting within total mental task heart rate analysis. CI = confidence interval, HR = heart rate, ME/CFS = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, n = number, SMD = standardized mean difference.
Figure 10
Figure 10
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on daily average heart rate. CI = confidence interval, ME/CFS = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, n = number of participants, SMD = standardized mean difference.
Figure 11
Figure 11
Effect of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on post-exercise heart rate recovery. CI = confidence interval, MD = mean difference, ME/CFS = Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, n = number of participants.
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