David Systrom, researcher, Brigham and Women's Hospital, USA

The problem is recognised as very disabling. In right heart failure or biventricular failure from lung disease or alcoholism if too much diuretic is given then not enough fluid is getting back to the heart for it to pump on. The person usually can barely lift an arm, let alone go to the toilet.

But I am a bit sceptical about calling this 'preload'. This is a catchy term developed in the 1960s together with 'afterload'. Neither are actually loads. Preload mostly seems to mean a low central venous pressure and I think it would be better to call it that, because if it is more than that, and it is likely to be more complicated, then it should be specified. I may be biased but the cardiologists who threw 'preload' into their conversations when I was a young physician tended to be showmen rather than clinical scientists.

 

That's really interesting. Thanks for sharing.

 

What symptoms would suggest preload failure?

Can I have it while still being able to do walks of up to 1 hour with only minor PEM? That's a lot less than other people of my age, but more than many patients.

I can also swim for a few minutes but cannot seem to increase my endurance even when doing it regularly. It feels like there is some physiological limitation that doesn't get better with training.

I get chest pain, palpitations and sensation of painfully overstimulated heart when doing too much activities or spend too much time upright. This lasts for hours, days, weeks. Sounds like sympathetic overdrive to me.
The immediate response to excessively intense exertion is becoming extremely tired and sleepy and lying down (despite the presumed sympathetic overdrive).

I can get a feeling of shortness of breath while doing activities, and dizziness after walking upstairs. Holding my breath almost immediately becomes unpleasant and hard to bear. There's clearly something wrong with my breathing and breath holding tolerance.

My heart rate is no longer consistent with POTS but is a little too high at rest.

I tire more rapidly and profoundly from exercise even compared to people who are much older than me. But the most noticable limitation is probably in the total amount of activity over the course of the day.

Hot weather makes the aforementioned things worse and especially causes initial orthostatic hypotension.

Would testing positive for preload failure lead to some useful treatments? I know Systrom tested pyridostigmine which had some positive effect but not in the longer term. Are there any other, established treatments?

 

I’ve now watched Systrom’s presentation in its entirety. I find it hard to reconcile some things. He strikes me as a serious person who doesn’t give off that used car salesman vibe that 99% of “CFS specialists” do. Yet, his statements don’t map onto the data shown on slides. He says preload failure is ubiquitous in this pt population. His word. If that’s so, hasn’t he solved the age old mystery of no biomarker for ME/CFS? This is supposed to be unambiguous evidence of organic pathology not seen in deconditioning studies. Who has attempted to replicate this? I mean, CPET is a mainstream medical test, not some new unproven technology like the nanoneedle.

Secondly, the Mestinon thing. I find it difficult to believe that a mainstream drug that’s been around forever has not been noticed before to be a successful treatment for autonomic dysfunction such as Pots. The results of the study on women don’t look clinically significant to me. Yet he continues to use this in the clinic. Also, why slice and dice your data and start talking about only women halfway through the talk? Could it be because none of the hypothesised associations are sig in the overall sample including men? One of the questions in the Q&A asked about men and the response was vague and unsatisfactory.

 

My understanding is that invasive CPET is a highly specialized test that is offered only in few clinics. Presumably very few people even know about its use in ME/CFS and LC although this is difficult to estimate because with LC things are evolving rapidly.

I heard from several other patients that had it done outside of Systrom's clinic and the findings were apparently replicated. In some cases it was the first time the doctors had ever done it on a person with ME and were surprised by the results.

That said, if a test has a very high rate of being positive that could also mean it's unreliable. I'm mentioning this because there is a theoretical possibility, not because I have a bad impression. Systrom comes across as a serious down-to-earth researcher.

 

The point is that this is mainstream technology accepted in mainstream medicine, not some highly speculative fringe science paper. If what he says is true, and remember he first published these results many years ago when we were still on the previous forum (the initial paper on unexplained dyspnea), it’s surprising that people are still being sectioned under the mental health act and generally ridiculed.

 

He says preload failure is ubiquitous in this pt population. His word. If that’s so, hasn’t he solved the age old mystery of no biomarker for ME/CFS?

Secondly, the Mestinon thing. I find it difficult to believe that a mainstream drug that’s been around forever has not been noticed before to be a successful treatment for autonomic dysfunction such as Pots.

Great points. However preload failure happens also in heart failure, mitral regurgitation and mitral stenosis, and it would not be enough on its own to signal ME/CFS, however, perhaps sensitive tests on the heart could be included in diagnostics? We don't yet know, presumably, what percentage of the ME pt population have preload failure.

Also, the approach to prescribing for ME/CFS hasn't really been 'try it and see what happens', at least in the UK. Unless it's in the NICE Guidelines it's not usually tried. And isn't it likely it will be of help to a specific subset of patients, as with other treatments. We are still only just able to discriminate between different groups in a lab (is it Montreal? And the genetics data anticipated might shed some light perhaps. I'm in a fog of hopefully now fading PEM here today), and I don't think that work has been replicated elsewhere yet? I'm asking my GP today to let me try mestinon to see if it helps as muscle weakness has been a big feature of my ME, disproportionate to other ME symptoms when I've been mild, and I have both orthostatic intolerance and a consistently good response to TVNS suggesting some vagus nerve involvement. Perhaps it will help.

 

100% especially as this appears to be accepted medical procedure and not fringe. And understood to be debilitating.

 

This is interesting; however, is this preload failure not a consequence of 'something'. It might be helpful to identify patients objectively from healthy folks, but this has to be downstream of? Infection? Immune issues? Autoimmunity? I doubt this will be unique to post viral conditions.... I hope it is the start of a new understanding and move forward.

 

There was also this case report of a woman with ME/CFS who was cured by an intervention to treat narrowing of the transverse sinuses. These are veins at the back of the head.

https://pubmed.ncbi.nlm.nih.gov/26623235/

 

Is this the sort of thing that could be tested for easily? Has it been ruled out for most pwME?