Abstract

In a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band. Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men. Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS.

Highlights

  • Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder characterized by medically unexplained and persistent fatigue

  • Heart rate and systolic arterial pressure were higher in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients compared with control participants (p < 0.05)

  • Our results revealed that male ME/CFS patients self-reported severe fatigue, autonomic dysfunction, decreased sleep quality, and increased anxiety and depression symptoms, together with increased higher heart rate and blood pressure values at rest compared with male healthy controls

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Summary

Introduction

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder characterized by medically unexplained and persistent fatigue. Symptoms fluctuating in frequency/severity during the natural course of illness include severe, disabling fatigue, as well as musculoskeletal pain, sleep disturbance, orthostatic intolerance, post-exertional 4.0/). A variety of studies have been performed to establish objective biomarkers of ME/CFS disease, including molecular imaging and neuro-functional imaging using magnetic resonance imaging (MRI), magnetoencephalogram (MEG), positron emission tomography (PET), or microRNA expression [3,4]. Since most of these techniques are expensive and unaffordable, other non-invasive procedures capable of associating a biomarker with fatigue and/or accompanying symptoms are being investigated. Heart rate variability analysis (HRV) could become an objective, non-invasive and easy-to-apply marker. Heart rate variability (HRV) is defined as the fluctuations in the time interval between consecutive beats [5]. HRV is considered an index of autonomic resilience, since it reflects the ability to recover from exposure to both physical and psychological stressors [7,8]

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