Cardiopulmonary Exercise Test Results Do Not Change Over Two Sequential Days in Patients with Chronic Fatigue Syndrome, 2026, Mancini, Natelson et al

[forestglip]

Cardiopulmonary Exercise Test Results Do Not Change Over Two Sequential Days in Patients with Chronic Fatigue Syndrome

Spoiler: Authors

Donna Mancini; Dane Cook; Danielle Brunjes; Tiffany Soto; Michelle Blate; Patrick Quan; Tadahiro Yamazaki; Anna Norweg; Benjamin Natelson

Background
Two consecutive cardiopulmonary exercise tests (CPETs) performed 24 hours apart is increasingly used to determine post-exertional malaise (PEM) and disability in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Declines in functional capacity on Day 2 reflect impaired recovery and PEM. However, reports have variably described a reduction in peak oxygen consumption (VO2) and/or VO2 at the anaerobic ventilatory threshold (VT). Given the inconsistent findings, we sought to replicate the studies performing sequential 2-day CPETs in ME/CFS and age and sex matched sedentary controls

Methods
Accordingly, we performed maximal bicycle ergometer CPETs on 2 consecutive days in 58 patients with ME/CFS (mean age 38.6 ± 9.6 yrs, BMI 24.1 ±3 .3 kg/m2, 11 men and 47 women ) and 25 age-matched sedentary control (CON) subjects (age 38.2 ± 9.9 yrs, BMI 24.2 ± 3.4 kg/m2, 5 men, 20 women). Peak VO2 was reported as the highest 30-sec average, VT was selected as the nadir of the VE/VO2 and PETCO2 curves, and VE/VCO2 as the slope throughout exercise.

Findings
For ME/CFS and CON subjects there were no significant changes in Peak VO2 between Day 1 and 2 studies (ME/CFS Day 1: 22.3 ± 5.4; Day 2: 22.5 ± 5.4 ml/kg/min; CON: Day 1: 23.4 ± 3.5; Day 2: 22.8 ± 3.6 ml/kg/min; NS).

Similarly, VO2VT and VE/VCO2 slopes were not significantly different between the ME/CFS patients and CON and on day 2 did not show any differences within or between groups. Peak heart rate was significantly higher in CON versus ME/CFS.

The level of perceived exertion was significantly greater at all levels of exercise on the Day 1 and 2 tests for ME/CFS patients versus CON.

Interpretation
Our data indicate that 2-day CPET provides exercise-related results that are the same in ME/CFS patients and in CON subjects. ME/CFS patients have greater perception of exertion throughout exercise and a lower maximum heart rate than CON. The data do not support using the 2 day CPET protocol to define PEM or disability.

Web | Frontiers in Physiology | Abstract only ahead of publication

 

[RainbowCloud]

I can’t for the life of me understand why PEM is rarely tested for 48 and/or 72 hours after as well when it’s widely reported as occurring then.

 

[Eddie]

I think this puts to rest the idea that the 2 day CPET is measuring some core feature of PEM. The small decreases in Vo2 max found in other studies were never large enough to convince me they weren't due to differences in time of day, sleep, food intake etc.. I do think it is plausible that the pain and discomfort experienced during PEM can have an impact on lowering Vo2 max. But in that case the test isn't providing any more useful information than simply asking if a patient is in pain.

The more interesting test for me is the invasive CPET run by Systrom. I seem to remember that an inability to increase heart rate might be related to the lower venous filling pressures in the heart. But it feels like we have been waiting a while for him to publish more data on the invasive test esp. v controls.

 

[ME/CFS Science Blog]

Looks like they failed to replicate the 2-day CPET results, although look forward to seeing the actual data.

The most replicated finding was workload at the ventilatory threshold which they don't report in this abstract.

 

[Hoopoe]

I find this hard to believe because I see next-day decline in performance (physical and mental) all the time in response to excessive exertion.

I suspect the CPET or this particular protocol is inadequate to measure the phenomenon. The reason may be that what counts is the cumulative exertion over the previous days, and a single CPET is just not "big enough" in comparison to everything else the patients are doing to shift the system in a meaningful manner. Also physical exertion is just one of several contributors. Exposure to sensory stimuli, mental effort and others also contribute.

And yes this inability to maintain performance over days/weeks due to aggravation in fatigue and symptoms is not something that the average healthy person seems to experience.