Deconditioning does not explain orthostatic intolerance in ME/CFS, 2021, VanCampen, Rowe, Visser

Sly Saint

Sly Saint

Senior Member (Voting Rights)
Deconditioning does not explain orthostatic intolerance in ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome)


Abstract
Background

Orthostatic intolerance (OI) is a frequent finding in individuals with myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS). Published studies have proposed that deconditioning is an important pathophysiological mechanism in various forms of OI, including postural orthostatic tachycardia syndrome (POTS), however conflicting opinions exist. Deconditioning can be classified objectively using the predicted peak oxygen consumption (VO2) values from cardiopulmonary exercise testing (CPET). Therefore, if deconditioning is an important contributor to OI symptomatology, one would expect a relation between the degree of reduction in peak VO2during CPET and the degree of reduction in CBF during head-up tilt testing (HUT).

Methods and results
In 22 healthy controls and 199 ME/CFS patients were included. Deconditioning was classified by the CPET response as follows: %peak VO2 ≥ 85% = no deconditioning, %peak VO2 65–85% = mild deconditioning, and %peak VO2 < 65% = severe deconditioning. HC had higher oxygen consumption at the ventilatory threshold and at peak exercise as compared to ME/CFS patients (p ranging between 0.001 and < 0.0001). Although ME/CFS patients had significantly greater CBF reduction than HC (p < 0.0001), there were no differences in CBF reduction among ME/CFS patients with no, mild, or severe deconditioning. We classified the hemodynamic response to HUT into three categories: those with a normal heart rate and blood pressure response, postural orthostatic tachycardia syndrome, or orthostatic hypotension. No difference in the degree of CBF reduction was shown in those three groups.

Conclusion
This study shows that in ME/CFS patients orthostatic intolerance is not caused by deconditioning as defined on cardiopulmonary exercise testing. An abnormal high decline in cerebral blood flow during orthostatic stress was present in all ME/CFS patients regardless of their %peak VO2 results on cardiopulmonary exercise testing.


https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02819-0
 
The number of patients in the abstract seems to have been incorrectly reported.

In the abstract, the authors report that 199 patients were included, but in the Results ("Participants"), they write:

Twenty-eight subjects of the group with a normal HR and BP (normHRBP) response during HUT (21%) showed a normal CBF reduction, while the remaining 105 (79%) showed an abnormal CBF reduction. All patients with POTS (n = 39) and dOH (n = 27) showed an abnormal CBF reduction, leading to a total of 171 patients to be studied.​

So 171 patients with objectively demonstrable OI* were included in the analyses, as confirmed by the titles of the figures in the paper, and the 28 remaining patients who did not qualify for OI per the tilt test were used for comparison.

However, this means the abstract is incorrect: it reports that "ME/CFS patients had significantly greater CBF reduction than HC (p < 0.0001)" and "An abnormal high decline in cerebral blood flow during orthostatic stress was present in all ME/CFS patients", when this held for only 171/199 included patients.

Also, none of the patients who were included used medication that modified their heart rate or blood pressure or compression clothing. This would have left only patients with POTS and orthostatic hypotension for whom treatment was not warranted because their condition was mild, or because it was not possible (e.g. with drugs such as beta-blockers, midodrine or ivabradine), to be included. 67 patients on such medication were excluded. Presuming all had POTS or OH and were more severe than those in the study, the results may have differed had they been included, but maybe not significantly so considering that 80/171 (46.7%) included patients were already severely deconditioned:

ehNjm7S.png


Despite this, it is interesting that a rather important number of ME/CFS patients had OI without POTS or OH in this study. This can also be seen in Lee et al's study: "Hemodynamics During the 10-Minute NASA Lean Test: Evidence of Circulatory Decompensation in a Subset of ME/CFS Patients". Does this suggest that autonomic dysfunction is not the only pathway to OI in ME/CFS?

* The authors define confirmed OI as:

Based on our previous study, we considered OI to be confirmed by CBF measurements if a reduction greater than 2 SD beyond the mean of the healthy volunteers [30]. This defines an abnormal CBF result as a > 13% reduction during tilt.​
 
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I'm jumping in here were I don't have the knowledge base but I want to make a remark I made once before. A while back I was reading (after googling) what NASA had to say about deconditioning after stays on the ISS. The information online from NASA was highly technical with a lot of data graphics but reading what was written I got the impression that while there were some physiological changes (muscles) that they did not consider the astronauts deconditioned and that recovery happened easily and relatively quickly.

This is of course me interpreting what I read. But it would be interesting to know more about what NASA knows with regard to OI and deconditioning. I think it would contradict the BPS cabal's fictional accounts based on their NOT research.

By which I mean to ask, apart from presuming deconditioning have they (the cabal) ever scientifically measured or even reviewed research on what constitutes actual deconditioning?

Apologies as I've just realised that this takes the thread away from the discussion of results in the paper.
 
Yes, this is an interesting study!
Sly Saint said:
Conclusion
This study shows that in ME/CFS patients orthostatic intolerance is not caused by deconditioning as defined on cardiopulmonary exercise testing. An abnormal high decline in cerebral blood flow during orthostatic stress was present in all ME/CFS patients regardless of their %peak VO2 results on cardiopulmonary exercise testing.
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I think this is the chart showing drop in cerebral blood flow for each group and that it does not appear to be correlated to the %peak VO2 (hence, not related to deconditioning).

Cerebral Blood Flow vs. VO2 -small.png
 
Snowdrop said:
the information online from NASA was highly technical with a lot of data graphics but reading what was written I got the impression that while there were some physiological changes (muscles) that they did not consider the astronauts deconditioned and that recovery happened easily and relatively quickly.

This is of course me interpreting what I read. But it would be interesting to know more about what NASA knows with regard to OI and deconditioning.
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this is a little complex to interpret. During the early space programme both NASA and Russia did extreme bed rest studies on earth on healthy volunteers as a proxy for deconditioning in space. They also studied astronauts when they returned from space.

These were all very small studies as they involved volunteers being confined to bed for many weeks and sometimes months. But the results were as you described, where recovery was relatively fast and normal after the bed rest period was over.

However, things have changed since then. Because deconditioning is an issue, astronauts now routinely exercise in space. So probably isn't safe to conclude too much from studies from the international space station, which involves people who are unusually fit and healthy and who have exercised (in a 0/very low gravity environment).

Even so, there's nothing in the studies to support the deconditioning model of illness. Somewhere, the late Bob wrote an absolutely brilliant letter addressing the deconditioning argument. I think it was in response to a paste paper that reported fitness results for the Pace trial (which found that there was no correlation between fitness and improvements in fatigue).

My understanding is that psychosocial enthusiasts have effectively now abandoned the deconditioning argument (even though it was explicitly the basis for the graded exercise approach in the Pace trial).

PS long time ago I posted quite extensive notes on deconditioning (and its failure as an explanation) on the Phoenix rising for (username Oceanblue). I honestly can't remember what I said or how I would find them.
 
Could some pose some sort of rationale that would be believed by others, regarding reduced CBF is due to deconditioning? In other words, can doubt still be successfully thrown at pwME just being deconditioned?

Thank you.
 
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DokaGirl said:
Could some pose some sort of rationale that would be believed by others, regarding reduced CBF is due to deconditioning?

Thank you.
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Is there even a definition, criteria or test for deconditioning?

Because it sounds like something that is asserted but never actually verified. That sure would solve a lot of our problems but it seems common knowledge that it's a vague concept and yet it's asserted as firmly as the fact that the Sun will rise tomorrow. Little difference between "you are deconditioned" and "you have psychological issues", a mere convenient assumption that may sometimes be true.

Really sounds like something that should have been done a long time ago.
 
rvallee said:
Is there even a definition, criteria or test for deconditioning?

Because it sounds like something that is asserted but never actually verified. That sure would solve a lot of our problems but it seems common knowledge that it's a vague concept and yet it's asserted as firmly as the fact that the Sun will rise tomorrow. Little difference between "you are deconditioned" and "you have psychological issues", a mere convenient assumption that may sometimes be true.

Really sounds like something that should have been done a long time ago.
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Very good points. Thank you @rvallee
 
rvallee said:
Is there even a definition, criteria or test for deconditioning?

Because it sounds like something that is asserted but never actually verified. That sure would solve a lot of our problems but it seems common knowledge that it's a vague concept and yet it's asserted as firmly as the fact that the Sun will rise tomorrow. Little difference between "you are deconditioned" and "you have psychological issues", a mere convenient assumption that may sometimes be true.

Really sounds like something that should have been done a long time ago.
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Spot on.

How hard can it be to define and set parameters for deconditioning? I've not seen this done. Surely the first or one of the first stages in the scientific process? And once defined, the hypothesis can be tested. E. G. Does Wessely school CBT/GET undo deconditioning? And do patients return to good health at the same time. Never tested, not even looked at to my knowledge. Should have been challenged by ethics committees, colleagues, peers, supervisors and editors. Little evidence of that
 
Art Vandelay said:
Exactly. Is there a list of symptoms for 'deconditioning'?

Moreover, I've never seen anyone from the BPS cabal explain how 'deconditioning' can cause ME/CFS symptoms such as sore/swollen lymph nodes for example.
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For a hypothesis to carry weight it has to explain, at least in part, a plausible mechanism. How undefined 'deconditioning' explains many ME symptoms is a mystery, especially the infectious type symptoms.

Much more plausible to suggest infection / infectious and / or immune disruption of some sort. Based on symptoms, it'd be hard to tell apart people with chronic infections and pwME. Ditto people with untreated immune deficiency. And clearly there are other causes of such symptoms too. Heterogeneous.

Need to move to using well defined and simple objective measures and away from symptoms and questionnaires about symptoms. And subtypes of patients.
 
rvallee said:
Is there even a definition, criteria or test for deconditioning?
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This particular study defined it as below. I don't think I've ever seen any of the usual BPS suspects offer a definition though, back when they were still arguing the deconditioning card (which seems to have been quietly dropped by most of them since).
Sly Saint said:
Deconditioning was classified by the CPET response as follows: %peak VO2 ≥ 85% = no deconditioning, %peak VO2 65–85% = mild deconditioning, and %peak VO2 < 65% = severe deconditioning.
Click to expand...
 
Ravn said:
This particular study defined it as below. I don't think I've ever seen any of the usual BPS suspects offer a definition though, back when they were still arguing the deconditioning card (which seems to have been quietly dropped by most of them since).
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Visser et al. used the same definition of deconditioning as Parsaik et al's 2012 article, "Deconditioning in patients with orthostatic intolerance", but the latter authors did not provide a reference to justify their choice of these cut-off values:

Methods

Definition of different variables.
POTS was defined as a symptomatic increase in HR on 70° passive tilt for 10 minutes done after 10 minutes of supine resting (head-up tilt [HUT]) ≥30 bpm. OI was defined as the development of previously defined symptoms of cerebral hypoperfusion or sympathetic activation with standing, but with a HR increment <30 bpm.1 Patients with VO2max <85% on exercise testing were considered deconditioned, whereas those with VO2max ≥85% were considered normal. Mild deconditioning was defined as VO2max between 85% and 65%, and severe deconditioning was defined as VO2max <65%.
​
This suggests either that those are considered standard values for exercise testing, or that they were arbitrarily chosen. In the latter case, the choice could have been made based on the cohort of young women in the study: "89% were women, and median age was 27.5 years (interquartile range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8)"

Interestingly, Parsaik et al. concluded:

Reduced VO(2max)% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.​

However, CBF reduction was not one of the autonomic indices that they analyzed (which comprised: quantitative sudomotor axon reflex test, HR response to deep breathing, phase IV of the Valsalva maneuver, Valsalva ratio, and thermoregulatory sweat test). By looking at this association, Visser et al's study provides evidence against Parsaik et al's claim that deconditioning may be central to OI, at least in ME/CFS.
 
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But surely VO2max is a measure of fitness: more specifically of endurance.

Deconditioning implies a change in an individual's level of fitness. Without a measure of what is normal for that individual, it is impossible to say if an individual is deconditioned.

Deconditioning also, as a term, implies no change in physical health. If one lung was removed, you could hardly expect the same level of fitness, and it would be ridiculous to put down any drop in fitness to deconditioning.

I can accept that astronauts could become deconditioned. I can't think of many other situations where the term could apply. A fit athlete could retire and become less fit – are they deconditioned?

The term just does not make sense to me.
 
Graham said:
But surely VO2max is a measure of fitness: more specifically of endurance.

Deconditioning implies a change in an individual's level of fitness. Without a measure of what is normal for that individual, it is impossible to say if an individual is deconditioned.
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Indeed, a comparison at the individual level would require having both pre-illness and current VO2max values. The former is not usually available, so the comparison is done with age and sex-matched reference groups:

As absolute oxygen consumption differs between males and females and are age related results are shown in percent of a reference group to enable comparison of both genders and a broad age range [34,35,36,37,38,39].
​
Graham said:
Deconditioning also, as a term, implies no change in physical health. If one lung was removed, you could hardly expect the same level of fitness, and it would be ridiculous to put down any drop in fitness to deconditioning.

I can accept that astronauts could become deconditioned. I can't think of many other situations where the term could apply. A fit athlete could retire and become less fit – are they deconditioned?

The term just does not make sense to me.
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I agree that the term is imprecise at best. One is conditioned to a certain activity level, but what activity level specifically is left untold by the term "(de)conditioning". Using a range of VO2max values from a reference group implies that one studied individual's fitness level, and by approximation their activity level, is expected to fall somewhere around the group's average (or not if they are deconditioned). Whether approximating one's general activity level by their fitness level is adequate can be questioned.

In your example, a fit athlete who retires and loses fitness would not be considered deconditioned because they would likely go back to the average levels of fitness (VO2max) and activity of their reference group, or even above if they continue exercising regularly. Compared to a general population of same age and sex, they were an outlier to begin with and they would exhibit regression to the mean. However, compared to other athletes, they would become deconditioned per both their reduced VO2max value (fitness) and physical/exercise abilities (activity).
 
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Ravn said:
This particular study defined it as below. I don't think I've ever seen any of the usual BPS suspects offer a definition though, back when they were still arguing the deconditioning card (which seems to have been quietly dropped by most of them since).
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So that being consistent with another paper from 2013 posted today sounds like a somewhat standard criterion.

But how do they know that this is a reliable definition? And how do they tell the difference if it's caused by a disease process? Whether that's ME, dysautonomia or, say, lung issues that are only caught if the right test is done? Or myocarditis? Aren't they just catching people who are ill? And do truly deconditioned people really show those things? Consistently? Even after returning to normal activity, which doesn't take long? And we find the same from people who were in the ICU for a long time, but those people were sick and/or injured, how do they tell the difference?

Seems very ad hoc, especially for something that is used so commonly.
 
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