Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With [ME/CFS], 2021, Nelson et al

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have been shown to exhibit altered ventilatory characteristics on the second of two progressive maximal cardiopulmonary exercise tests (CPET) performed on consecutive days. However, maximal exercise can exacerbate symptoms for ME/CFS patients and cause significant post-exertional malaise. Assessment of heart rate (HR) parameters known to track post-exertional fatigue may represent more effective physiological markers of the condition and could potentially negate the need for maximal exercise testing.

Sixteen ME/CFS patients and 10 healthy controls underwent a sub-maximal warm-up followed by CPET on two consecutive days. Ventilation, ratings of perceived exertion, work rate (WR) and HR parameters were assessed throughout on both days. During sub-maximal warm-up, a time effect was identified for the ratio of low frequency to high frequency power of HR variability (p=0.02) during sub-maximal warm-up, and for HR at ventilatory threshold (p=0.03), with both being higher on Day Two of testing. A significant group (p<0.01) effect was identified for a lower post-exercise HR recovery (HRR) in ME/CFS patients. Receiver operator characteristic curve analysis of HRR revealed an area under the curve of 74.8% (p=0.02) on Day One of testing, with a HRR of 34.5bpm maximising sensitivity (63%) and specificity (40%) suggesting while HRR values are altered in ME/CFS patients, low sensitivity and specificity limit its potential usefulness as a biomarker of the condition.

Open access, https://www.frontiersin.org/articles/10.3389/fphys.2021.771899/full

 

I was a participant of this study and it is a followup analysis of some of the other data collected (original manuscript from 2019: https://doi.org/10.1186/s12967-019-1836-0)

I remember discussing the hypotheses with Max Nelson, key hypotheses were maximal rate of heart rate increase at exercise onset (rHRI) and was slower HR recovery post-exercise, similar to what they had observed in fatigued athletes. But after initial results, and a subsequent presentation, they had less confidence in this hypothesis. I was a little disappointed when there was no mention of this stuff in the original manuscript, but Max was (then) a PhD student and presumably just wanted a published study under his name before trying to publish this detailed analysis.

Notably, there were also no day to day differences in heart rate variability (HRV) measures such as LF/HF ratios. HRV in general is a fairly non-specific measurement and can simply indicate that patients had lower levels of fitness compared to controls, rather than indicate anything about pathology.

One frustrating omission in both manuscripts is the observation that the rate of change of RPE (perceived exertion on the Borg Scale) had a non-linear increase at the Vt1 (first Ventilatory Threshold aka Gas Exchange threshold). This may seem like a trivial observation, given that it has been observed in all of the CPET studies I have seen (regardless of whether the participants were ill, healthy controls or athletes), but none of the ME/CFS 2 Day CPET studies have reported RPE curves (if they measured it or reported it at all).

Further comments on the discussion - the authors don't seem to fully appreciate the role of central fatigue and the connection with muscle afferents, and it's effect on ventilation kinetics - to the point where I'm considering having a chat with Max... A lack of effect on "peak HR, peak WR and peak RER" is because VO2Max is still submaximal in terms of motor unit utilisation - specifically, the limit in the rate of oxygen delivery to the muscle by the heart/lungs, rather than a neuromuscular limit of performance. When there is fatigue, the participant has to put in more effort (upstream of the motor cortex itself) to achieve VO2Max - which leads to increased RPE, but the VO2max limit should be similar unless there is something pathologically wrong.