Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical...

Discussion in 'Other Health News and Research' started by Kyla, May 17, 2016.

  1. Kyla

    Kyla ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ

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    This isn't about ME, but some of the patients had POTS, and this is discussed in the context of exercise testing. Thought the results might be of interest to some here.
    I have pulled out one of the relevant sections and quoted it (below the abstract)

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860548/
    (Open Access)



    Discussion of the results for POTS patients:

     
  2. JaimeS

    JaimeS Senior Member

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    Yeah, I saw this too -- or else a nearly identical article -- and starting looking up incomplete filling of ventricles. It was an interesting path to travel down.
     
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  3. ryan31337

    ryan31337 Senior Member

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    Hard work to read but really interesting. The take away point of this study according to the summary I saw was that it is further proof that POTS is not deconditioning, with a difference shown in right atrial pressures between POTS and deconditioned individuals, suggestive of impaired venoconstriction.

    I thought all that was well understood already, considering the standard treatment choices for POTS (midodrine etc.) but I guess its not well proven and that's why they're used off-label still...
     
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  4. JaimeS

    JaimeS Senior Member

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    I've had this same experience often, @ryan31337 ... what the patient community and the doctors who work closely with them 'know' is often not proven in the medical lit.... yet.
     
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  5. anciendaze

    anciendaze Senior Member

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    Please note that this was a retrospective study done on hundreds of patients who had invasive CPET for reasons considered valid clinical indications. If anyone is aware of a single ME/CFS patient who has had iCPET I would like to know about them.

    These patients would meet a cardiologist's definition of exercise intolerance because they exhibited dyspnea during exercise, which most of us do not. CPET testing of ME/CFS patients typically checks for pulmonary problems first, and these patients would be referred to different doctors. Exactly what happens to them then is a good question.

    One cohort of these patients was given IV saline, presumably to correct possible hypovolemia, which also shows up in ME/CFS. Another cohort was tested both without and with this preloading to see how it affected results. Their ability to benefit from this, in terms of increased stroke volume, appeared to be reduced.

    We have no idea of what the patients experienced in the days after testing because that is typically not a concern for cardiologists. We don't know if they resembled ME/CFS patients in having PEM/PENE. I suspect they did.

    Problems seen in ME/CFS include endothelial dysfunction, which might well be responsible for problems with venous return. We tend to think of the heart as a pump and vascular systems as inactive pipes, but this underestimates the amount of activity, particularly in tiny blood vessels where it is hard to observe with traditional cardiovascular measurements. Anyone who has experienced vasovagal syncope should know behavior of blood vessels is quite active. I am now curious about pulmonary capillary wedge pressure in ME/CFS patients.

    This paper reported decreased stroke volume in patients, which also happens in ME/CFS. We don't know about pressures requiring invasive tests because these are not done unless there is a perceived risk to life, which is not there in ME/CFS.

    What I miss most here is any data on the ability of heart muscle fibers to relax, as shown best by IVRT. I would predict that this was longer than in healthy patients. Such impairment could point to mitochondrial dysfunction and viral or autoimmune disease.
     
  6. JollyRoger

    JollyRoger Senior Member

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    @anciendaze
    @JaimeS
    @ryan31337
    I know it's an old thread but may I ask you a question.
    Could it be that mitochondrial dysfunction is not the cause but a side effect of the low blood volume?
    Check the picture....


    It's because I had a gradual onset of me cfs and had several checkups (already checking my heart for years).
    In every echo my heart got smaller and the vena cava diameter (is used to check the blood volume and is increased in heart failure) also got smaller.
    I also noticed in the beginning that after drinking vast amounts of water i was free of symptoms.
     

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  7. JaimeS

    JaimeS Senior Member

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    Low blood volume is another one of those 'all ME/CFS doctors know' but it's not well-documented. Looking into this myself actually.
     
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  8. ryan31337

    ryan31337 Senior Member

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    Hi @anciendaze,

    I had a PR member inbox me recently who had abnormal CPET tests similar to mine - he went on to have an iCPET under care of Dr Systrom. I'll message them and see if they're happy to share details with everyone.

    I am currently on the waiting list for another test, which I know only as 'EPR' - I got this from being copied into correspondence between my POTS cardio & the consultant that runs the complex physiology testing lab. I wonder if this might be Exercise Pressor Reflex? Seems to be pertinent in my case as I have episodes of hypertension after exertion/orthostasis, low AT/VT and fit squarely in the hyperadrenergic POTS camp.

    This is quite an interesting read: http://ajpheart.physiology.org/content/309/9/H1440
    It discusses the practise of artificially restricting blood flow to muscles whilst exercising, in order to accumulate metabolites like lactic acid at lower intensity exertion than would normally be required - apparently this environment can lead to greater muscle growth and strength. But it runs the risk of exaggerated sympathetic nervous system activation....sounds familiar huh :whistle:
     
  9. JollyRoger

    JollyRoger Senior Member

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    Blood flow restriction training - some guys in my gym did it (many moons ago)
    They loved the burning...... and I have it 24h a day now.....WWWAAAAHHHHH!


    That would explain the PEM because low ATP was also found in depression and they have no problems post-exercise.
     
    Last edited: Jun 18, 2017
  10. anciendaze

    anciendaze Senior Member

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    @JollyRoger,

    I think episodic hypovolemia is part of dysautonomia. Drinking lots of water only temporarily deals with part of this, since it causes a drop in concentration of electrolytes like sodium or potassium. This has also caused me to pass out. Now, before I go out, I not only drink water, but also take a SaltStick capsule, as if I were going to do heavy exercise. You have to take this before you get in trouble because absorption of electrolytes through the stomach is slow.

    The problem with ATP is not how much, but when and where it is released. Some tests show increased ATP, but not from the cell's own mitochondria. I suspect this is from a standard response to localized hypoxia, after dropping the O2 they carry, erythrocytes will dump ATP in regions that remain hypoxic. This enables local cells to survive an hypoxic episode through localized anaerobic metabolism. ATP is also a major biochemical signal affecting vasoconstriction, etc.

    This goes along with evidence of low anaerobic threshold during exercise. One problem with testing for this is that some cells in the body can be in anaerobic metabolism while most are not. Tests are able to measure VO2max, but we have little to show localized anaerobic activity except accumulation of lactates.

    @ryan31337,

    I'll be interested in any results of iCPET. I have no experience with EPR.

    My own problem seems to fit in with neurally-mediated hypotension, not hypertension. However, if you call me in 5 hours before minor surgery, then leave me sitting in the waiting room for that time, when you finally prep. me you will find systolic bp of 160. If I had not been straining to keep functioning, I would have passed out. This is typically interpreted as hypertension, and the prescription would be drugs to lower mean bp. If they did this, I would frequently be unable to stand up.

    I'm afraid this is a common practice with elderly patients, leaving them bedbound. My first episodes began in my teens and 20s, but now I fit the elderly profile doctors expect. I've regularly seen elderly people have episodes of syncope 2 to 3 hours after taking bp medication. Repeated episodes of cerebral hypoperfusion are likely to result in general neurological deterioration, but the medication is justified as avoiding a risk of stroke, which is life-threatening.

    The problem is not "too high" or "too low", it is poor regulation of bp. No simple pill treats that.
     
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  11. Gingergrrl

    Gingergrrl Senior Member

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    This was a fascinating thread and I just discovered it. In my case, I have autoantibodies where my lung tissue itself is normal but my respiratory muscles (and other muscles) are weakened. Because of this, I cannot really use 02 saturation or arterial blood gas testing to accurately detect the level of dyspnea that I experience.

    I also have POTS since 2013 (confirmed 100% by TTT at Stanford). My doctor now considers me to have "Autoimmune POTS" b/c of autoantibodies that affect the beta adrenergic receptors (in addition to the ones that cause muscle weakness).

    I have never found fluid loading to be of any help and my attempt at IV saline in 2014 led to flash pulmonary edema and being rushed to the ER. I also tried Mestinon that same year and had a horrible reaction. But I get great benefit from Atenolol and Midodrine. And I have had the greatest benefit from high dose IVIG, which definitely does cause a temporary increase in fluid volume, but I do not believe that this is the mechanism in which it is helping me vs. that it is temporarily knocking down the pathogenic autoantibodies (even though they keep coming back :mad:).

    I have never had a CPET test but I am so curious if it would accurately reflect my situation? The article says it can distinguish between cardiac and pulmonary causes of dyspnea, but can CPET assess for respiratory muscle weakness as the cause of dyspnea if caused by autoantibodies? I do not know the answer myself but was curious @JaimeS what you think since you are actively studying and researching this stuff and you have a solid grasp of it all (unlike me :D)!

    I found this quote very interesting from @anciendaze because I assumed that everyone with ME/CFS would have dyspnea during actual exercise like a CPET test but this now makes me think that I am wrong. If most CFS patients would not have dyspnea during a CPET test (and this has been shown in studies), then I know with absolutely certainty for the first time, that CFS is not my diagnosis. I would be gasping for air with chest pain before the first minute of the test was done (or at least I would have been prior to eleven months of IVIG). Now I cannot say for sure if I could last one minute (it is possible?) but I would definitely have dyspnea even if the test would no longer send me to the ER.
     
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  12. JollyRoger

    JollyRoger Senior Member

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    Regarding my idea of low blood volume causes mitochondrial dysfunction I found this in a paper of Julia Newton:

    Additionally, it is also possible that reduced vascular runs off (related to autonomic dysfunction), resulting in decreased vascular flow into and out of the muscle following exercise which may have an effect on O2 delivery, potentially limiting the function of the three-enzyme complex pyruvate dehydrogenase complex (PDC) [91].
    {>>>>>>>
    PDC/PDH were the inhibited enzymes that they found in Norway.

    Hypoperfusion of the brain, mitochondrial dysfunction through low 02 , peeing a thousand times a day.... would be a good explanation for all these stuff
     
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  13. JaimeS

    JaimeS Senior Member

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    So plain old CPET would not be able to determine cause of dyspnea, IMO.

    However, iCPET:

    Boldface mine -- from http://pulmvasc.pitt.edu/patient-care/icpet/ -- looks like it can do that!

    Hmm. Well, I've all the symptoms for ME/CFS as per CCC (almost literally ALL of them) -- and I had dyspnea straight afterwards. They had to support me off the bike, doing my usual gasping for air. I swore "this passes, just wait..." I said I didn't need oxygen, but they kept asking me until I said 'yes' (I think they needed my permission to administer, since I was conscious.) So.

    Also, it's only second-day CPET that is 'supposed' to show abnormalities; but my lactic acid was several-fold times higher than normal. The exercise physiologist told me there was no way my response was due to deconditioning.

    We all have mechanisms behind our illness and yours and mine may be a tad atypical. However, the dx still holds, IMO.

    -J
     
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  14. Gingergrrl

    Gingergrrl Senior Member

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    That was my understanding, too, but I was not certain.

    Interesting but it sounds very invasive :nervous:. Has anyone on PR ever had an iCPET test?

    Okay, then you would be more like me! This is what I thought except for when I read AD's quote above that most PWC's would not have dyspnea w/exercise, it confused me.

    I guess the bottom line is that I remain confused if ME/CFS is my diagnosis or not but I guess it really does not matter as much as I would like to know for sure!
     
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  15. JaimeS

    JaimeS Senior Member

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    It only matters if another diagnosis would give you more treatment options...
     
  16. ryan31337

    ryan31337 Senior Member

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    Regular CPET can certainly assess for respiratory muscle weakness and is often combined with pulmonary function & blood gas tests to guide analysis. I think the most obvious indication of a lung or neuromuscular disease is that end tidal CO2 does not decrease towards the end of the test. They'll also be indications from your breathing patterns & maximum work rate. Its just suggestive of a problem there though, its unlikely to determine what the underlying pathology is.

    I understand that the big benefit of iCPET to us is its ability to differentiate between issues of oxygen utilisation e.g. mitochondrial myopathy, and oxygen delivery problems e.g. preload failure due to dysautonomia. A non-invasive CPET would simply show reduced O2 pulse, but O2 pulse depends on both stroke volume and the a-v O2 content difference. Stroke volume is reduced in dysautonomia, a-v O2 content difference is decreased in MM. So by having arterial and mixed-venous catheters in place to measure the venous PO2 and the a-v O2 content difference you can determine which is the biggest limitation.

    There's an outside chance some of us with abnormal day 1 CPETs have MM, but its more likely to just be reduced stroke volume on orthostasis/exercise (normal at rest). This is diagnosed by Dr Systrom as preload failure, which he considers a result of dysautonomia.

    In between relapses I had years of good physical function and normal (immediate) response to exercise, no dyspnoea just PEM the next day. Its only during relapses, when i've had significantly worsened OI, that dyspnoea has been a problem.

    I would hazard a guess that Day 1 CPET abnormalities are likely linked to significant autonomic dysfunction. Which in my experience is a lot more disabling and less manageable than the energy recovery/PEM issues associated with mild/moderate ME, so would perhaps get chalked up as primary POTS or whatever and maybe be excluded from ME studies?
     
    Last edited: Jun 20, 2017
  17. JollyRoger

    JollyRoger Senior Member

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    We know that Dr scheibenbogen found autoantibodies in some cfs patients... one of them is the autoantibody against β2-adrenergic receptors.

    Now I found this:

    During exercise, α1-adrenergic receptors in active muscles are attenuated in an exercise intensity-dependent manner, allowing the β2-adrenergic receptors which mediate vasodilation to dominate.

    And a study:

    Physical exercise, β-adrenergic receptors, and vascular response

    Maybe cfs is an autoimmune disease against vessel receptors.

    The vessels should be an active "organ" to pump the blood.

    Anyone tried swimming (water pressure maybe helps a bit?)????
     
  18. Binkie4

    Binkie4 Senior Member

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    Last edited: Jun 22, 2017
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  19. JaimeS

    JaimeS Senior Member

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    @Binkie4 -- Find the [ / Q U O T E .] If it's at the end, move it to where you want the quote to stop. It looks like you have [ blood volume is another one of those 'all ME/CFS doctors know' but it's not well-documented. Looking into this myself actually.../....QUOTE..]

    That red bracket needs to move here:

    blood volume is another one of those 'all ME/CFS doctors know' but it's not well-documented. Looking into this myself actually.[... /.QUOTE..]

    LOL trying not to make the coding actually work by doing weird stuff!

    Generally, tradition decides what it is best for doctors to know. The CBC in the US (complete blood count) contains a limited number of markers for a limited number of disorders, meaning that people with diseases discovered earlier on tend to be able to find out what's the matter with them swiftly, while people with disease identified or better-described in the modern era are usually left flailing about in medical limbo for years as physicians wonder which test to try, next. In universities, the education of doctors often lags decades behind, taught by people who feel they know all they need to know about medicine and have not kept abreast of the latest findings in their field -- or, to be fair, people who have to publish papers to survive and also be a university lecturer, which leaves them little time for following ideas they are not working on, themselves.

    Our only hope so far is self-education. I am working hard and so are some other devoted scientists on your side, but meanwhile it's important to find out everything that you can, yourself.
     
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  20. Binkie4

    Binkie4 Senior Member

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    Thank you @JaimeS .

    I will work on your quotes explanation but until yesterday, I thought I had it sussed!

    It does seem strange that UK medical training even today contains nothing about blood volume for a cardiologist. Nor does it cover the haemorheological aspects. As you said ( almost)- do it yourself!
     
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