Penfold, Sophie Maria, Cunningham, James, Whelan, Pauline et al. · Pathophysiology : the official journal of the International Society for Pathophysiology · 2025 · DOI
This review looked at 17 studies examining the link between fatigue and heart rate variability (HRV)—a measure of how well your nervous system is working. The researchers found that people who feel more fatigued tend to have imbalanced heart rate patterns, suggesting their autonomic nervous system (the part controlling automatic body functions) may not be working properly. ME/CFS patients were the most studied group, making this particularly relevant to understanding fatigue in this condition.
This review synthesizes evidence that autonomic dysfunction—measurable through HRV—is associated with fatigue across conditions, with ME/CFS being the most studied group. Understanding this connection could validate objective biomarkers for fatigue and help clinicians recognize autonomic involvement in ME/CFS pathophysiology, potentially guiding future treatment strategies targeting autonomic function.
This review establishes correlation, not causation—we cannot determine whether autonomic imbalance causes fatigue or whether fatigue causes autonomic changes. The heterogeneity in methods and small number of studies per condition means results may not apply uniformly to all ME/CFS patients, and the review does not establish HRV as a diagnostic marker for fatigue or ME/CFS specifically.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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