Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study

Abstract

Background: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear.

Purpose: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness.

Methods: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1).

Results: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%).

Conclusion: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

Fig 1. Mean (95% CI) cardiopulmonary exercise testing values for participants with ME/CFS and otherwise healthy controls.

Plots in the left column show values for the full study sample (ME/CFS = 178; Controls = 169) and plots in the right column show values for the fitness-matched subgroup (ME/CFS = 99; Controls = 99). Data are expressed as 20, 40, 60, 80, and 100% of peak oxygen uptake. Significant findings from the linear mixed effects models of the entire exercise response are denoted with *. a. Ventilatory parameters—ventilation ($\dot{\mathrm{V}}\mathrm{E}$), respiratory frequency (f_R), and tidal volume (V_T). b. Heart rate parameters—heart rate (HR), oxygen pulse ($\dot{\mathrm{V}}{\mathrm{O}}_2/\mathrm{HR}$), and chronotropic index (CTI). c. Efficiency related parameters—ventilatory equivalent for oxygen ($\dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}{\mathrm{O}}_2$), ventilatory equivalent for oxygen ($\dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{C}{\mathrm{O}}_2$), and oxygen uptake/work rate ($\dot{\mathrm{V}}{\mathrm{O}}_2/\mathrm{WR}$). d. Ratings of perceived exertion (RPE) on the Borg 6–20 scale.