Cardiac Output–Cerebral Blood Flow Relationship Is Abnormal in Most ME/CFS Patients with a Normal Heart Rate & Blood Pressure ..., 2024, van Campen

The only problem is the divsion is post-hoc based on the same variable. Given 91% were in the abnormal group (which is quite high given the lack of specificity of ME/CFS diagnosis) it doesn't seem as much a big deal, if the data is genuine.

 

Is the "Stichting CardioZorg" a clinic that patients would commonly attend to obtain a diagnosis / standard management of ME/CFS or is it somewhere that already-diagnosed patients would only attend to obtain further evaluation & treatment for orthostatic intolerance specifically? The authors do acknowledge potential referral/selection biases but curious as to how great those are likely to be.

 

The sense I get is that it trends towards the orthostatic intolerance bucket. In the study they assessed the records of people who had underwent a tilt table test at the clinic and then determined if they qualified for an ME/CFS diagnosis. So the patients weren't sent to the clinic specifically for ME/CFS. While this may overestimate how common this finding is in ME/CFS patients, I do think it is still a important result. Do we know if large changes in cardiac output (25-40% decreases) are correlated to decreases in cerebral blow flow in healthy people?

 

Well there seems to be a expected spread along the x-axis for Cardiac Output, which is what you'd expect as heart just doesn't instantly pump more. There are a couple little jumps that are not expected.

The main split is in CBF (y axis).

 

Good point.

I looked at another of this group's studies: Worsening Symptoms Is Associated with Larger Cerebral Blood Flow Abnormalities during Tilt-Testing in ME/CFS, 2023, van Campen

I'm guessing both these studies are looking at the same general set of historical patient records, with maybe a few differences. But this other study looked at CBF reduction for two visits per patient, so presumably there is data there that's not in this study.

I added the red arrow. It seems like there is a gap at around the same location there too, consistent across groups and visits. If someone got worse, they jumped across the gap.

 

It's the patients asking for a referral. GP's don't know anything about ME/CFS. Even a chronic fatigue "specialist" I met didn't know these cardiologists.
I think both groups you describe would ask for a referral.

 

Another of their studies that looked at CBF reduction.

Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography, 2020, van Campen et al

The current thread's study only looked at people with ME/CFS but normal HR and BP. This study had 247 ME/CFS with normal HR/BP, 62 ME/CFS with delayed orthostatic hypotension, and 120 ME/CFS with POTS. I'm not sure if the records of those with normal HR/BP were included in the thread's study, but at least this study has participants in two groups that were not included.

The following chart has CBF reduction on the x axis. There's not as clear of a gap, but it does still look like two clusters separated at about -10%. This is a little higher than the middle of the gap in the thread's study (around -13%), but also this chart is showing reduction at mid-tilt, while the plot from the thread's study is showing end-tilt. It makes sense that there would be a smaller reduction (higher cluster division) at mid-tilt. And maybe the clear gap doesn't open up until end-tilt.




A similarly high percentage of people with ME/CFS had greater reductions than the controls in this study as well. 82% with normal HR/BP vs the thread study's 91% (although these may have largely been some of the same patients), 98% with dOH, and 100% with POTS.

 

Another paper from them:

Cerebral Blood Flow Is Reduced in Severe ME/CFS Patients During Mild Orthostatic Stress Testing. van Campen et al. 2020

This is only on 19 people with severe ME/CFS, no controls.


All had a greater than -20% drop in CBF. And there was a correlation between CBF reduction and cardiac index reduction. I'm not sure if "cardiac index" and "cardiac output" from the thread's paper are the same thing.

 

Same group:

Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in (ME/CFS)Patients: A Randomized Crossover Trial, 2021,Rowe



I'm pretty sure the colors are swapped, since the paper's conclusion is that there is less reduction in CBF if wearing stockings. I emailed the author, she thinks they were swapped too.

Without stockings everyone reduced more than 15% (average 25%), which is consistent with not having participants in the "gap" of the thread's study between about 10-15%. With stockings, there were reductions that were right on the area of the gap, basically centered right on it, with an average reduction of 14%.

Correlation between cardiac output and CBF reductions here too.

Looks like quite the improvement in CBF reduction from stockings as well. And this thread's study shows a large proportion of people with ME/CFS but no HR or BP abnormalities have large reductions. So might be useful for those people as well.

 

I am pretty sure this is relevant.

On the other hand, I would be somewhat surprised if this is specific to ME/CFS.

The degree of dysregulation and of the resulting hypoxia might be somewhat specific, though?

This research needs replication, but the results should hardly surprise anyone.

If patients for decades say they feel better on electrolytes and IV saline, 'specialists' can talk all they want about how that makes no sense physiologically.

One of my layman theories has forever been that ME/CFS patients do not have *enough* blood vessels, and that they are too lax.

This simple idea could potentially explain much of the "low CO = low CBF" findings.

 

Cardiac index is cardiac output divided by body surface area. So L/min/m2.

 

Also, I checked with the author. They have no idea why there's a gap.

 

The thread for the preprint is here.

 

Thread for published paper at The Cardiac Output–Cerebral Blood Flow Relationship Is Abnormal in Most Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with a Normal Heart Rate and Blood Pressure Response During a Tilt Test (2024, Healthcare)

 

But it doesn't. The RAAS responds to fluid and salt content in circulation through haemodynamic pressures and through ionic concentrations in kidney. So it will respond to IV saline. And it does, as is routinely seen when we give IV saline in acute medical situations. Salt and water taken by mouth will have exactly the same effect once they have been absorbed into circulation. Salt and water by mouth always are absorbed into circulation, even if excess to requirements. You never lose salty water per rectum as a result of ingesting too much, only if you have a diseased gut. You always excrete the excess via the kidney. So IV and oral saline will impact on the RAAS in exactly the same way.

 

Interesting to read people's success with these interventions for their OI but FWIW, I've tried oral fluid/salt/electrolytes/rehydration solution, IV saline and waist-high compression tights, all with zero effect.

 

Same.

 

I am not sure if it is a success story as such and has many caveats due to my own personal health problems.

I had ME for a couple of decades and just had a fleeting look at the literature every now and again - to find out nothing had advanced....so kept doing what seemed to worked for me, which was pacing and rest. For many years I had chosen to be on a low salt, low carb diet - not strict but just to maintain my weight as can't aerobically exercise. I also have hypothyroidism treated with a slightly higher thyroxine dose compared to normal as my endocrinologist thought it might help. Unclear if it did and now I am on a normal dose. I also have interstitial cystitis and constipation and had major symptoms of menopause that took a while to settle with HRT. I have always had low blood pressure, no symptoms until a couple of years ago.

A few years ago, I joined a local FB group of one of our main ME support providers. Many of the pwME were on electrolytes/compression stockings and many had had a good response. I thought golly I have been asleep at the wheel! Just to explain: the NZ health system is different from the UK, our GP's are private and independent of hospital specialists. Although they would probably consult NICE guidelines, they have the freedom to prescribe and recommend whatever they like for patients if they can justify it medicolegally, which includes what other GP's prescribe for their clients with ME, guidance from USA ME/CFS clinics eg Bateman Horne or a clinical study. We have few expert GP's in ME, very difficult to get a consult with them and they are expensive. Also to note many of the pwME from my FB group on this protocol were also on LDN which I am not interested in taking yet as I would prefer more research. Some also had diagnosed POTS and were on fludrocortisone.

I was having a lot of problems with my ME, dizziness, cognitive problems due to OI, in PEM for months etc and needing to spend all day in a recliner following having covid (omicron). I was very concerned if I did nothing I would stay in the recliner. My blood pressure was low, including the pulse pressure and my GP rang the hospital physician who said refer her to the Post Infectious Fatigue Clinic...which I waited for a appointment for 18 months then they cancelled it. I had a new GP and we decided I should first see a cardiologist to rule out heart problems due to covid. I had a normal NASA lean test, echo and ECG so he asked when was my last "decent walk" and advised exercise with their electrophysiologist which I declined.

My GP had not heard of this symptomatic treatment for Orthostatic Intolerance, so I explained it and she thought it was worth giving it a trial. So using Bateman Horne Clinic protocol I increased my salt, and fluids (electrolyte sachets) 2-3 L/day and compression stockings. I had to have thigh high medical grade stockings due to the frequent urination. She would monitor my electrolytes and renal function. I also got an abdominal binder but didn't feel I needed it later on. Once starting, all my dizziness and worst of my cognitive problems disappeared within days. I started being able to be more upright and get back to doing things I enjoyed. It was a revelation, I also got less urinary symptoms and constipation. I have considered some of this improvement may have been from mild dehydration but I don't think it is just that. My blood and pulse pressure improved and I am now normotensive.

So it did make a big impact on my functioning, not a miracle cure but I could be on my feet longer and go to the local shops on the bus but I still would get PEM if overdid it or with an infection and over the last few years I have become fully housebound and my OI is limiting (can't stand to cook for long and now rely on my partner to do major meal cooking). But I can now do a lot more than what I was doing, which was not a lot in my recliner/bed. I never could get the salt intake recommended, (some people take salt pills and I just didn't feel I could commit to that), so I probably take about half the recommended salt but the electrolytes definitely help cognitively and the OI (as well as improving bowel and bladder function).

One useful additional improvement was arthralgic knee pain which got severe and interfered with my rest when in PEM - this completely went, which I think was due to the support of the joint. I used to also get a leaden feeling in my calves when in PEM and this also disappeared. May have been due to supporting my aging veins but the reduction in pain is another motivation to put on my very tight compression stockings, first thing in the morning. When in PEM with low energy and strength, I use a donning device (Medi-butler) to help put on these compression stockings but when improved just need special grippy gloves. I buy electrolytes from the supermarket rather than getting the prescribed funded ones through my GP (oral rehydration salts) as they taste horrible to me. I can get electrolytes, with or without sugar and use a Waterminder App to monitor intake. It is hard to keep up a high salt diet so have decided to salt my food liberally and also drink salt rich vegetable juice (V8) with meals. It takes time and energy to learn the daily schedule of filling and cleaning drink bottles but I do feel the end justifies the means.