Trial Report The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2024, Jason

[Dolphin]

https://www.mdpi.com/2075-4426/14/3/238

The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
by
Leonard A. Jason
1,*,
William J. McGarrigle
2 and
Ruud C. W. Vermeulen
3


1
Department of Psychology, DePaul University, Chicago, IL 60614, USA
2
Department of Psychology, University of Kentucky, Lexington, KY 40508, USA
3
CFS Medical Center, 1114 Amsterdam, The Netherlands

*
Author to whom correspondence should be addressed.
J. Pers. Med. 2024, 14(3), 238; https://doi.org/10.3390/jpm14030238

Submission received: 10 January 2024 / Revised: 14 February 2024 / Accepted: 21 February 2024 / Published: 23 February 2024



Abstract

Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often experience autonomic symptoms.

In the present study, we evaluated 193 adults seeking treatment for ME/CFS, who were recruited from an outpatient clinic.

The participants completed a head-up tilt table test to assess two common types of orthostatic intolerance, namely, postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH).

During the tilt test, 32.5% of the participants demonstrated POTS or OH.

The participants with either of these two common types of orthostatic intolerance were found to have more problems with sleep and post-exertional malaise as assessed by the DePaul Symptom Questionnaire; these patients also reported more physical and health function limitations.

The implications of the findings are discussed.

Keywords:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; tilt table test; orthostatic intolerance

https://twitter.com/user/status/1762165300542276056

 

[EndME]

I cannot fathom why this study doesn't have a control group (which is cheap and easy to have in such a study). Given the abundance of results that already exists on this topic I would consider the results worthless without a control group.

There will probably also be some additional bias. Anbody knowledgeable and interested in pursuing the "POTS angle" will probably be far more likely to visit the clinic by van Campen/Visser rather than the CFS Medical Center in Amsterdam.

 

[EndME]

“The sample consisted of 193 adults with a physician report of ME/CFS and referred to an outpatient clinic in the Netherlands (the CFS Medical Center in Amsterdam).”

I’m not sure what that means. According to their webpage anybody can visit the CFS Medical Center in Amsterdam (where a diagnosis is given) and they don’t do a rigorous medical examination to look for other possible underlying medical problems (it looks as if they actually don’t do an examination at all).

In fact, the CFS medical center whose "ME/CFS patients improve 86%" of the time due to their treatment according to their homepage and who also treat Long-Covid, offer their treatment via a subscription based model (6 months of “treatment” for 950€). So I would take the accuracy of their diagnosis with a large pinch of salt (of course many people with ME/CFS will still visit this clinic simply because they have no other option).

Note: R. Vermeulen lost his licence as a physician in 2011 (see also this discussion). I was under the impression that one should try to steer away from him and instead try to engage with Pekelharing.

 

[Hutan]

The head-up tilt table test [12] served as an autonomic assessment of orthostatic intolerance. During the test, which lasted 20 min, an appropriately sized cuff was placed on the participant’s upper arm and the participant was instructed to remain still and silent in the supine position for 10 min. At that time, blood pressure and pulse were measured with a sphygmomanometer (Omron M6). After 10 min, the table was raised to a 70-degree head-up tilt for another 10 min. The test was terminated after 10 min in the tilted position or sooner if the participant reported complaints indicating insufficient cerebral perfusion.
The participants were labeled as positive for orthostatic intolerance (OI+) if they demonstrated either POTS or OH during the head-up tilt table test. OI− indicated that the patient did not have POTS or OH. POTS was defined as a heart rate increase of ≥30 bpm that is sustained (i.e., lasting at least two consecutive minutes) within 10 min of the tilt; OH was defined as a sustained decrease of at least 20 mmHg in systolic blood pressure or 10 mm Hg of diastolic blood pressure within 3 min of the tilt

10 minute tilt, POTS defined by heart rate increase >=30 bpm
OH decrease <=20mmHg in systolic blood pressure or <=10 mmh/g of diastolic blood pressure within 3 mins of tilt

Yeah, no controls...

 

[ahimsa]

I'm curious about one type of abnormal tilt table test result - a sudden drop in blood pressure that happens later on - that was not covered by this study.

From the method section (my bolding):

POTS was defined as a heart rate increase of ≥30 bpm that is sustained (i.e., lasting at least two consecutive minutes) within 10 min of the tilt;

OH was defined as a sustained decrease of at least 20 mmHg in systolic blood pressure or 10 mm Hg of diastolic blood pressure within 3 min of the tilt

What about a drop in blood pressure that happens later? It looks like the tilt lasted 10 minutes in this study. What about drops in blood pressure that can happen 11-40 minutes after the start of the tilt table test?

Many names have been used for this - vasodepressor syncope, neurally mediated hypotension (NMH), delayed orthostatic hypotension. I don't care about the name, but I do wonder - is this problem so rare that it should just be ignored? I know several folks on this forum have mentioned having this type of orthostatic intolerance.

I have a POTS diagnosis now, but when I was first tested (1995) my heart rate did not increase by enough to meet POTS criteria. But on the tilt table I did have a sudden plummet in blood pressure after 20 minutes. I passed out. This was after about 10-15 minutes of increasing pre-syncope symptoms.

How many folks in this study got symptoms on the tilt table test but did not qualify for either POTS or OH diagnosis? Would they be labeled as not having any OI (OI-) when they may have a version of OI that was not detected?

EDIT: I do need to read the whole paper fully since I may have missed something. It's hard to hold multiple things in my head.

EDIT #2: I just found an error. I read the line "During the test, which lasted 20 min ..." and didn't see that the tilt part of test was only 10 minutes. I've corrected the error.

 

[ahimsa]

I'm curious about one type of abnormal tilt table test result - a sudden drop in blood pressure that happens later on - that was not covered by this study.

I did find some comments on this issue in the discussion section:
(added line breaks)

It is possible that the low rate of 32.5% demonstrating POTS or OH could be due to not including other forms of OI, such as vasovagal syncope.

It is also possible that cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia [20].

It is also plausible that given the high percentage of patients with POTS or OH that were either working or in the student status, this sample had relatively less impairment.

If this is the case, we speculate that the head-up tilt test may be more effective at detecting OI among more severely impaired patient cohorts, such as those within tertiary care settings.

I guess my main question is this: If you're going to do a study like this, why restrict the tilt duration to only 10 minutes?

 

[Eddie]

I cannot fathom why this study doesn't have a control group (which is cheap and easy to have in such a study). Given the abundance of results that already exists on this topic I would consider the results worthless without a control group.

I am genuinely curious why is a control group useful in such a study? To me it seems like the purpose of this paper was to figure out what percentage of pwME also meet the criteria for POTS. If a number of controls had a positive tilt table test all that seems to say is that those people would also qualify for a diagnosis of POTS. Given that POTS is just a label and tells us very little about the underlying pathology it seems like anyone who fulfils the criteria now has POTS by default. Perhaps where a control group would have been useful in answering the question: is POTS more common in ME/CFS than the general population. What would that tell us though?

I also wonder if a 30bpm increase is the most useful in indicating a pathological problem? A 30bpm increase clearly isn't normal otherwise POTS as a label wouldn't exist. However, I wonder how well the heart rate increase correlates with whatever the underlying issue(s) is. Are there any good studies looking at the frequency of POTS in the general population? I also don't know how you would validate such a test without knowing more about the underlying cause of POTS.

 

[Hutan]

I think a well-matched control group is useful in studies like this. Even if there is some information about OI issues in the general population as determined by tilt tests, there might be specifics that make things different in this study.

Perhaps there is something about the disease group - the age range, or the co-morbidities for example that isn't well represented in the general population data. Probably there will be some things that aren't consistent from study to study - how long do people rest horizontal before the test, what angle is the tilt, what is the temperature of the room? what time of day is the study done? how soon after a meal? How long is the tilt? how do you word your questions about symptoms and what symptom data do you collect? What criteria do you apply regarding BP and heart rate?

If you just accept some general population data about incidence, then you don't have the opportunity to control all those variables.

 

[EndME]

I am genuinely curious why is a control group useful in such a study? To me it seems like the purpose of this paper was to figure out what percentage of pwME also meet the criteria for POTS. If a number of controls had a positive tilt table test all that seems to say is that those people would also qualify for a diagnosis of POTS. Given that POTS is just a label and tells us very little about the underlying pathology it seems like anyone who fulfils the criteria now has POTS by default. Perhaps where a control group would have been useful in answering the question: is POTS more common in ME/CFS than the general population. What would that tell us though?

I also wonder if a 30bpm increase is the most useful in indicating a pathological problem? A 30bpm increase clearly isn't normal otherwise POTS as a label wouldn't exist. However, I wonder how well the heart rate increase correlates with whatever the underlying issue(s) is. Are there any good studies looking at the frequency of POTS in the general population? I also don't know how you would validate such a test without knowing more about the underlying cause of POTS.

For me the question isn't so much whether someone has POTS or not, but whether that actually means anything meaningful at all and/or whether it has meaning in regards to ME/CFS. As you say, POTS is just a label that tell us nothing. As you state a well chosen control group can tell us whether or not POTS is more common in ME/CFS than in the general population (or in people with certain conditions), that alone is very meaningful, but having a control group could additionally further tell us something about it's distribution (general population vs ME/CFS in terms of age/BMI/co-morbities etc). It would tell us whether this label is worthy of anything or not at all. A sizeable protion of ME/CFS research and funding goes towards POTS, it's part of some diagnostic criteria, sometimes even part of recruitment criteria for studies or used as end-point in studies. Should these things be the case, should there be even more funding and focus given it's a "hard measurement" or should there be less focus or where should this POTS research be directed to, to make it more meaningful?

I also wonder if a 30bpm increase is the most useful in indicating a pathological problem?

That is precisely what I'm thinking. It's awesome to have a "hard measurement", but what if this measurement is no different to differentiating people with ME/CFS by the colour of clothes they wear? It's clear to me, and backed by all studies, that a tremendous amount of people with ME/CFS report orthostatic problems. It's less clear to me whether that actually correlates well with the here specified blood pressure and heart rate measurement within the here described setting. Does it correlate with other known problems such as chronotopic incompetence or OH? Or is this an entirely different pathology? Is an alternative cut-off in regards to BPM and heart rate more meaningful in patients with ME/CFS than in the general population, does the angle of tilt or time-duration of testing matter more in patients with ME/CFS?

I don't know how much a study with a really good control group would have given us, because there is no control group at all, but if the control group were to report being perfectly healthy and had a 30bpm increase as often as those people who have ME/CFS and report orthostatic problems and there would be no obvious differences in those people in the general population for which this is the case, then I would be far more inclined to say that this specific 30bpm increase, via this procedure, means nothing and vice versa in the opposite case.

Of course there's a lot of questions that can be asked about POTS in the general population as well. Is it more common in less active individuals, is it more common in deconditioned people, is it more common in people with a higher BMI/age, is it similar to diabetes in the sense that there are 2 different types (i.e. one being some kind of autoimmune-like phenomenon and the other being predominately due to being unhealthy), is the one more transient/self-resolvent than the other and do they respond differently to treatments including exercise, which is what most people prescribe for POTS?

I'm not too well versed in all the POTS literature myself and I'm sure some of my above question are redundant and will have been answered somewhere, but from what I've seen the 30bpm measurement does not correlate well with symptomatic burden of general POTS patients at all and I've commonly heard the phrase "POTS is named after it's most benign symptom". Should we be using additional or even different recruitment criteria and trial end-points in POTS trials and studies (for example the Covid POTS Efgartigmod study is additionally using the Malmö questionnaire)?

That's a lot of questions by me and even with a control group this study couldn't have answered all these questions, but these are some of the questions some answers have to be found too (and there's probably much better questions by far smarter people than me).

Without a control group I don't see how this study adds anything to our understanding of ME/CFS and/or POTS, because we already have several results stating "very roughly so and so many people with some sort of fatigue (because I can't see how exactly this is an ME/CFS study) have POTS based on a decent or less rigorous, as is the case here, recruitment.". From what I can tell this appears to be a somewhat unsatisfactory study, or at least it isn't particularly well written, having a control group would have at least offered some control over this less rigorous methodology. A lot of this isn't too specific to POTS either and would apply similarly to most Long-Covid studies.

The reason why I emphasised control group, instead of something different here, is because having a control group in this specific study would be very cheap, easy and hardly require any additional effort.

 

[Jonathan Edwards]

That seems a good summary of the problem @EndME.

I wonder if there is deeper confusion still. The title of paper is 'Measure of Autonomic Function' but is this valid?

My understanding is that if you stand up and your blood pressure falls (OH) that shows that your autonomic system is not responding adequately. Whether this is actually abnormal or not I am not sure because I have always had this problem from a low chair, although not from lying (the physiology is obviously complicated).

But postural orthostatic tachycardia indicates that the autonomic system is responding, and more so than normal maybe. Moreover, it is not clear what it is responding to. It might be a response to an incipient failure to maintain blood pressure but equally it might be a response to feeling bad for any other reason.

So my first thought is that a tilt table test is not in any simple sense a test of 'autonomic function'. I am always wary of jargon like that anyway.

The second thought is that POT may be a manifestation of two quite different things. One may be a brisk and adequate autonomic response to a slight drop in BP or maybe central venous pressure without even dropping BP. The other may be a sympathetic response to feeling awful on standing for any other reason including not being well. I rather suspect that when we are ill for any reason - an infection or after an operation or in kidney failure or whatever - that pulse rate may well rise with the distress, effort or anxiety of going upright.


On the control issue: yes, you need a control group because the conditions and thresholds for the test will vary with the temperature of the room, the politeness of the staff, and goodness knows what. But I think a much more serious problem is doing a study like this on an outpatient population with an expectation of finding something. It would be much better to rely on something like the ME Biobank cohort where recruiting was much more population based and a whole bank of bank are documented without emphasis on expectation of any one particular measure being different. It is not just easy to bias data, it is very hard not too if you are deliberately looking for something.

 

[Eddie]

Thanks for taking the time to respond EndME. I think your points are very reasonable and help clarify the issue for me. As always so many questions have yet to be answered. In this case, I would not be surprised if the only reason the tilt table is used for "POTS" is because it is an abnormality that can be clearly measured. It can nice to have some tangible abnormality both for the patient and the doctor even if that is not particularly helpful.

I have always thought that at least a subset of POTS may be some sort of compensatory mechanism for reduced cerebral blood flow. I haven't look hard enough to see if the literature supports this, but it makes sense that the heart would beat faster if the brain starts to receive less blood. Perhaps the autonomic system is working as intended in this case.

 

[Eddie]

This video seems to be a pretty good summary of the literature already out there. These are the kind of result the NIH should have tested in their study. It also seems like the controls in a majority of these studies had far lower orthostatic symptom burden than the NIH found.

 

[wigglethemouse]

The Bateman Horne center published their "POTS" study of the 10 minute NASA lean test several years ago. Lost in the details were that the controls also had a ~30% diagnosis rate too. I see the same error of not including controls in almost all POTS studies.

This study diagnostic criteria for POTS

POTS was defined as a heart rate increase of ≥30 bpm that is sustained (i.e., lasting at least two consecutive minutes) within 10 min of the tilt;

The "official" POTS diagnostic criteria for Dysautonomia international.

The current diagnostic criteria for POTS is a heart rate increase of 30 beats per minute (bpm) or more, or over 120 bpm, within the first 10 minutes of standing, in the absence of orthostatic hypotension.[\QUOTE]

 

[ME/CFS Skeptic]

During the tilt test, 32.5% of the participants demonstrated POTS or OH.

Do they report the percentage for POTS and OH separately? Couldn't find it in the paper.