Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS, 2021, Joseph et al

https://journal.chestnet.org/article/S0012-3692(21)00256-7/fulltext


EDIT: also available here:
https://www.sciencedirect.com/science/article/abs/pii/S0012369221002567

 

RAP is the blood pressure in the right atrium of the heart (one of the four chambers in the heart). I'm not sure how important a healthy blood pressure is in there but it seems like a disturbingly large difference between patients and controls. Something is very wrong.

I'm not sure I understand what peripheral left-to-right shunting is, as I'm only finding explanations for regular left-to-right shunting.

This seems like a potentially very important study.

 

I'm not convinced there are many insights to be gained by comparing patients to controls on a single CPET. Several of the observations could simply reflect the fact that the individuals have different activity (and fitness) patterns to controls. I'd be more excited about a low-flow scenario, rather than high-flow, since VO2Max is a measure of how much oxygen can be delivered to the muscle. The observation suggests these participants are not actually reaching a true VO2Max.

Instead, I'd propose some sort of self-controlled study where patients perform worse on a particular physiological threshold that would otherwise be replicated in healthy controls is necessary for insights to identify cause-effect relationships.

edit- merged posts

Note that VO2Max is always achieved at high blood pressures - especially in trained athletes. This is more evidence (besides the very low peak heart rates) that these patients didn't actually achieve a true VO2Max.

They're suggesting that the veins and arteries are dilating too much, so that the blood is simply shunting through the capillaries with no resistance. I am not convinced by this argument, though if there is a loss of blood volume being circulated due to blood pooling elsewhere in the periphery, then this can limit performance. Note that unlike the veins/arteries which are regulated by the autonomic nervous system, capillaries regulate their own dilation locally to maintain flow.

 

Again, most likely this is a mitochondrial issue.

 

Full text anyone?

 

The Journal pre-proof is available

https://twitter.com/user/status/1361237793171726339

 

Thanks

 

Thanks for sharing. I'm not really sure what they're trying to say. Too brainfogged to properly read and understand it. Is it that ME has many exercise intolerance phenotypes. Are they considering POTS, SFN and fibro similar or even the same? In what way would ME differ from these other conditions?

 

Those would be good questions for the authors!

In the manuscript they claim overlap between the conditions:

But SFN was only found in 1/3 of patients (which is why they claim there may be more than one 'flow' profile):

The suggestion of perivascular myocyte dysfunction is interesting, the citation is 37:
Quantitative assessment and correlation of sympathetic, parasympathetic, and afferent small fiber function in peripheral neuropathy.
https://pubmed.ncbi.nlm.nih.gov/10836618/

But that manuscript doesn't really explain it at all.

Use of the word perivascular reminded me of the pericytes too, though their role in microcirculation is controversial.

 

Thank you for digging a bit more into the paper. What is also not clear to me if they feel exercise intolerance is the same as PEM seen in ME. It's an interesting paper but confusing.

 

It definitely isn't the same thing. They only mention PEM with regards to the case definition.

 

A short email exchange with dr. David Systrom:

Anil:

Systrom:

Anil:

Systrom:

Anil:

 

What I don’t understand is in the table of baseline characteristics they say out of 160 ME/CFS patients, 31% had SFN, 33% had POTS and 22% had fibromyalgia.

They then state that between 32-50% of all patients with fibromyalgia have SFN and a similar figure is also found in POTS (they report 38%).

So how do we know that the SFN found in 33% of their patients with ME isn’t due to them also having either a diagnosed or undiagnosed comorbidity of POTS and FM?

Am I missing something? I guess I’d like to see the breakdown of SFN stats in the ME patients who definitely didn’t have a co-morbidity of POTS or FM.

I have all three diagnoses so what’s my risk of SFN? It’s too much for my brain fogged brain.

 

@Grigor - many thanks for contacting Dr Systrom and sharing his email with us.

It kind of make sense now that he views the diseases and maybe the underlying pathology as overlapping but with nuances, whatever that means.

He said somewhere that he’s mainly treating ME patients with a dysautonomia pattern. So I wonder if he’s just homing in on a subset of us?

Or maybe the SFN is just a secondary consequence of the underlying disease process as seen in diabetes, but it’s not present in everyone. It still doesn’t address the root cause though. Only offers potential symptomatic management for those affected.

 

"similar diseases w/ nuances"?

I've known a few people with FM irl, and not one of them experienced PEM or anything close to what I have.

Hasn't exercise been shown as an effective therapy for pwPOTS?

 

POTS has been understood & described as the "final common pathway for a number of overlapping pathophysiologies".

In the context of simple, isolated deconditioning as a cause of POTS its not unreasonable to assume exercise therapy will be effective. But this isn't the case for people like us, deconditioning will be a very small factor, if at all.

 

I imagine that's related to this work:
https://www.s4me.info/threads/infla...utoantibodies-2021-gunning-grubb-et-al.19055/

 

I returned to running again after 6 years of PVFS and felt very much improved. I wasn't deconditioned at all and picked up right where I left off and felt great. . . except I had delayed PEM ever time.

 

PEM is a pathophysiology with symptoms that ebb and flow, but it’s not "gone" just because you don’t have bad symptoms one day. You don’t have "a diabetes." or "a migraine".