The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test, 2025, van Campen et al

J

John Mac

Senior Member (Voting Rights)
Abstract
Background/Objectives: Orthostatic intolerance is prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), CBF is regulated complexly, and cardiac output (CO) is an important determinant of CBF. A review in HC showed that a 30% reduction in CO results in a 10% reduction in CBF. In contrast, we showed in ME/CFS patients with a normal HR (HR) and blood pressure response during a tilt test that CO and CBF decreased to a similar extent. The relation between CO and CBF in ME/CFS patients with postural orthostatic tachycardia syndrome (POTS) is unknown. Therefore, the aim of this study is to assess the relation between CBF and CO, in ME/CFS patients with POTS.

The methods used in this retrospective study analyze this relation in a large group of patients. We also analyzed the influence of clinical data. A total of 260 ME/CFS patients with POTS underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO2. We measured CBF using extracranial Doppler flow velocity and vessel diameters obtained with a General Electric echo system, and suprasternal aortic flow velocities were measured using the same device. We recorded end-tidal PCO2 using a Nonin Lifesense device.

Results: End-tilt HR and the HR increase were significantly higher in the patients with a %CO reduction ≥ −15% than in the other group. End-tilt CO was higher and the %CO reduction was lower in patients with %CO reduction ≥ −15% than in the other group. CBF data (supine, end-tilt and the %CBF reduction) were not different between the two patient groups. The use of HR increases and %SV reductions were not as discriminative as the %CO reduction.

Conclusions: In ME/CFS patients with POTS during tilt testing with measurements of both the CO and the CBF, two different patterns were observed: (1) appr. two-thirds of patients had an almost 1:1 relation between the %CBF reduction and the %CO reduction. (2) Appr. one-third of patients showed a limited reduction in CO together with a substantial increase in HR. In these patients, there was no relation between the CO and CBF reduction. These data suggest the presence of a hyperadrenergic response.

https://www.mdpi.com/2077-0383/14/11/3648
 
Paper said:
End-tilt CO was higher and the %CO reduction was lower in patients with %CO reduction ≥ −15% than in the other group.
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The %CO reduction was lower in the group with a lower %CO reduction?

Again some interesting separation:
upload_2025-5-22_16-27-40.png upload_2025-5-22_16-28-3.png

Plot below from their study on people with ME/CFS and normal HR and BP responses, where I was intrigued about why the patients cleanly split into two distinct clusters: those whose cerebral blood flow didn't decrease much and those whose CBF did decrease a lot. In this thread's study on pwME who have POTS, it seems to be a clean separation into two groups, but separated on cardiac output and not CBF.
upload_2025-5-22_16-36-50.png

Edit: It looks like maybe in the other study if you plotted a histogram of just CO reduction, it might make two clusters there too.
 
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I overlaid the plot from this study with the one from the other study. I changed the colors so all the people from this study (ME/CFS + POTS) are green and all the ME/CFS without POTS from the other study are red. Blue is healthy controls from the other study.

It looks like the main clusters from both disease groups have almost identical distributions. And each disease group has another distinct cluster, and these clusters are also distinct from each other.
upload_2025-5-22_19-47-6.png
 
forestglip said:
I overlaid the plot from this study with the one from the other study. I changed the colors so all the people from this study (ME/CFS + POTS) are green and all the ME/CFS without POTS from the other study are red. Blue is healthy controls from the other study.

It looks like the main clusters from both disease groups have almost identical distributions. And each disease group has another distinct cluster, and these clusters are also distinct from each other.
View attachment 26310
Click to expand...
Look neat analysis

For the benefit of those of us not keeping up with this work, would you be able to explain what we are seeing here that is important, preferably spelling out the acronyms for CBF and CO, which muddle my brain?

I am interested in CBF and the CO work, and these findings look like they might be important. But I am struggling to understand what the data says is happening in biological terms.

Thanks (if you can).
 
Simon M said:
Look neat analysis

For the benefit of those of us not keeping up with this work, would you be able to explain what we are seeing here that is important, preferably spelling out the acronyms for CBF and CO, which muddle my brain?

I am interested in CBF and the CO work, and these findings look like they might be important. But I am struggling to understand what the data says is happening in biological terms.

Thanks (if you can).
Click to expand...
Unfortunately, I don't think I could do a good job explaining it as I don't fully understand the paper. But a few bits: CBF is cerebral blood flow, or how much blood is flowing into the brain per minute. CO is cardiac output, or how much blood the heart pumps per minute. They did a tilt test, and looked at how much these variables, and a few others, changed after being tilted upright. It appears that in everyone with POTS, their cerebral blood flow decreased between around 20 and 40%, but there was a group whose cardiac output also decreased around 20 to 40% and a group whose cardiac output didn't change much. In the group whose cardiac output decreased, their heart rate increased significantly more.

What any of this means, I'm not really sure. They talk about this pointing to a "hyperadrenergic response" in POTS in the abstract, but I haven't had the energy to try to read the discussion and understand what they mean.

I mainly posted the charts because the distributions caught my eye. Typically, I think biological measurements are more messy, but they've shown a clear separation into two clusters, which seems to indicate there's not a smooth spectrum of the disease, but two distinct disease states, and no in between. They showed something similar in the study of ME/CFS without POTS as well, except there's a third distinct cluster of not much cerebral blood flow reduction and not much cardiac output reduction.

And the 100% separation based on cerebral blood flow reduction between POTS in this study and healthy controls in the other study is interesting. Though I'm not sure if having large cerebral blood flow reduction is considered criteria for inclusion in this study.

Edit: Spelled out acronyms
 
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forestglip said:
What any of this means, I'm not really sure. They talk about this pointing to a "hyperadrenergic response" in POTS in the abstract, but I haven't had the energy to try to read the discussion and understand what they mean.
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They are saying the second group — who had a smaller change in CO during tilt (red in their Fig 2) — is indicative of a hyperadrenergic response, whereas in the other group (blue in their Fig 2) there is an almost 1:1 relationship between the change in cerebral blood flow and cardiac output. They say this might be due to endothelial dysfunction, which limits compensatory cerebreal vasodilation. In healthy patients this vasodilation means you get a smaller cerebral blood flow reduction per unit decrease in cardiac output.
 
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forestglip said:
I overlaid the plot from this study with the one from the other study. I changed the colors so all the people from this study (ME/CFS + POTS) are green and all the ME/CFS without POTS from the other study are red. Blue is healthy controls from the other study.

It looks like the main clusters from both disease groups have almost identical distributions. And each disease group has another distinct cluster, and these clusters are also distinct from each other.
View attachment 26310
Click to expand...
So even for people with POTS their cardiac output really isnt increasing much. Maybe just max 10%. So the increase in BPM doesn’t necessarily mean an increase in CO.
 
forestglip said:
Unfortunately, I don't think I could do a good job explaining it as I don't fully understand the paper. But a few bits: CBF is cerebral blood flow, or how much blood is flowing into the brain per minute. CO is cardiac output, or how much blood the heart pumps per minute. They did a tilt test, and looked at how much these variables, and a few others, changed after being tilted upright. It appears that in everyone with POTS, their CBF decreased between around 20 and 40%, but there was a group whose CO also decreased around 20 to 40% and a group whose CO didn't change much. In the group whose CO decreased, their heart rate increased significantly more.

What any of this means, I'm not really sure. They talk about this pointing to a "hyperadrenergic response" in POTS in the abstract, but I haven't had the energy to try to read the discussion and understand what they mean.

I mainly posted the charts because the distributions caught my eye. Typically, I think biological measurements are more messy, but they've shown a clear separation into two clusters, which seems to indicate there's not a smooth spectrum of the disease, but two distinct disease states, and no in between. They showed something similar in the study of ME/CFS without POTS as well, except there's a third distinct cluster of not much CBF reduction and not much CO reduction.

And the 100% separation based on CBF reduction between POTS in this study and healthy controls in the other study is interesting. Though I'm not sure if having large CBF reduction is considered criteria for inclusion in this study.
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Thanks very much for that. I was also struck by the clean separation for biological variables – like you say, that’s pretty rare. Unless there’s a selection criteria effect.

I’m still struggling little to understand the biological big picture and how important this is in the illness. But a link between cardiac output, pots and cerebral blood flow makes a lot of sense intuitively.

(Btw, I do know what the acronyms mean, I just find it confusing to read so many CBFs and COs together especially as, like Trish, I can’t help reading CO as carbon monoxide)
 
Simon M said:
Thanks – and I just didn’t want you to think that I hadn’t even bothered to read the abstract (where the acronyms are spelt out) before asking a question!
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I have specific problems with acronyms, so thanks to those who raised the issue. I haven’t worked out the pattern, though I struggle to learn news ones, can’t cope when there are a number of possible alternatives and just plain forget ones I ought to know.
 
Utsikt said:
Wouldn’t that be an increase because of the double negative?
Click to expand...
forestglip said:
The %CO reduction was lower in the group with a lower %CO reduction?

Again some interesting separation:
View attachment 26303 View attachment 26304

Plot below from their study on people with ME/CFS and normal HR and BP responses, where I was intrigued about why the patients cleanly split into two distinct clusters: those whose cerebral blood flow didn't decrease much and those whose CBF did decrease a lot. In this thread's study on pwME who have POTS, it seems to be a clean separation into two groups, but separated on cardiac output and not CBF.
View attachment 26305

Edit: It looks like maybe in the other study if you plotted a histogram of just CO reduction, it might make two clusters there too.
Click to expand...


Now I’m confused. They label the axis for example Decrease in CO. But mostly show negative percentages.

If the decrease in CO is -10% is that an increase? Or by decrease do they just mean that most patients had a negative value. Either way, very confusing.
 
Yann04 said:
Now I’m confused. They label the axis for example Decrease in CO. But mostly show negative percentages.

If the decrease in CO is -10% is that an increase? Or by decrease do they just mean that most patients had a negative value. Either way, very confusing.
Click to expand...
A lot of double negatives, but I think in general they're referring to actual decreases.
 
Yes I think the paper would have been easier to read if they'd written "change" instead of decrease or reduction in a number of places.

"%CO decrease >=-15%" is a bit tough to parse.

Also noting:

Figure 2 shows the relation between the %CO reduction and %CBF reduction in the two groups. In patients with an abnormal and large %CO reduction (<−15%), the relation was highly significant: %CBF reduction = 0.8291 × %CO reduction − 5.789; R 2 = 0.645; p < 0.001. In patients with a limited %CBF reduction (≥−15%), the slope was not significantly different from zero.
Click to expand...

should read "In patients with a limited %CO reduction"
 
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