Frontiers review - Chronotropic incompetence an overlooked determinant of symptoms and activity limitation in ME/CFS (prov. 2019) Davenport et al

Snow Leopard said:
Apart from the initial standing process, how exactly?
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If you are going up an incline, like a hill, it might happen. Its not an issue with treadmills at incline because the head is not actually rising. You would most likely have an issue running up stairs though. If the head is physically rising then OI is potentially an issue.
 
alex3619 said:
If you are going up an incline, like a hill, it might happen. Its not an issue with treadmills at incline because the head is not actually rising. You would most likely have an issue running up stairs though. If the head is physically rising then OI is potentially an issue.
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Again, please explain how?
 
alex3619 said:
If you are going up an incline, like a hill, it might happen. Its not an issue with treadmills at incline because the head is not actually rising. You would most likely have an issue running up stairs though. If the head is physically rising then OI is potentially an issue.
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Could this explain (amongst others) why taking stairs feels so darn exhaustive?
 
Wonko said:
If I work really hard at resting then I can get my HR down to high 60s, occasionally, more often low to mid 70s, but I have to be well rested for that, and anything more than a few minutes upright will send it at least into the high 90s. Once it's been like that for a few minutes it rises to low 100s even if I'm not doing anything. If I then do stuff it's 115-130. This is an improvement on how it used to be.

And so it goes.

How long this takes may, but only may, depend on how 'rested' I am, but once my HR is high even lying down immobile doesn't cause it to drop much, for quite a while - in fact it's often higher when lying down after 'exertion' (e.g. standing up long enough to make a cuppa - that sort of 'exertion').

I'm still trying to get a handle on what's going on, but it seems to depend, at least partially, on something I am not monitoring.

I've tried seeing what effects eating, different types of food, not eating, altering the timing and duration of sleep, adding in a few seconds of 'high intensity' exercise (a few reps of a minimum weight deadlift every couple of days), varying durations of 'low intensity' exercise (lurching).

The results make no sense e.g. 3 reps of deadlifts actually seem to reset my HR down to high 70s - low 80's, no matter what it was before, but walking, that raises it, and it stays elevated for anything from 5 hours to days, even whilst sleeping.

It's nonsense.

So the above paper, runs counter to my experience. If it is valid for all PwME then I ain't one, no matter what my symptoms suggest..
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This is very similar to my experience @Wonko

I try to avoid "activity" (physical, cognitive, emotional) in the morning as these activities increase my HR. But when I then lie down my resting HR is elevated, usually for the reminder of the day. As a result any further activity leads to higher HR than if I was rested. I find this more tiring. This elevated HR can also impact on the following nights sleep.

HR monitoring has been very useful as I've been able to identify a ceiling of average HR to best maintain symptom stability.

I now take Fludrocortisone (for orthostatic hypotension) and low dose BB (bisoprolol). The combination of these two reduces the scale of the HR response.

Prior to taking the meds I also had what felt like adrenaline surges (often early on in a rest period) which would result in elevated HR, irrespective of what I was doing, for hours or occasionally days. I would lie on the floor with my legs up on the bed trying to calm my HR for as long as my back could tolerate. Paced breathing only made things worse.

The meds have helped a lot.

I think it is possible that my SNS is over active and over sensitive. I felt like I was constantly living in a state of "high alert". The smallest stimulus would trigger an exaggerated response. It made my life a misery for 18 months.

I've always felt Pocinki's "Dysfunction Junction" article makes quite a bit of sense. https://www.healthrising.org/forums...-ans-autonersysme-cfs-by-dr-alan-pocinki.404/
 
Snow Leopard said:
Again, please explain how?
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OI typically kicks in when the head is rising. The brain compensates for falling blood pressure in the head by sending signals via the autonomic nervous system to adjust vascular tone and heart function. When I pass out from OI, complete collapse, its when I am getting up too fast only rarely. Going up stairs is my number one trigger. The brain has failed to perform adequate autonomic regulation. Now some of that might also be from direct peripheral issues, such as small fiber polyneuropathy, heart preload failure, and so on, but that does not change the outcome. Gravity and upward momentum plays its part in orthostatic intolerance.

Prolonged standing has a different mechanism, in which blood appears to slowly pool in the lower legs due to gravity and inadequate vascular regulation.

The conundrum for me is this ... I don't pass out in elevators. I don't know why. Maybe someone has some ideas? Is it because its a steady increase, and acceleration rather than velocity is the issue? This seems likely but I am far from sure.
 
Inara said:
Could this explain (amongst others) why taking stairs feels so darn exhaustive?
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Walking up stairs is likely to be a huge energy demand as well. You are fighting gravity. I don't have the stats, but I bet some exercise physiologists do.
 
I may have a (simplified) idea why walking steps might be more troublesome with POTS than just standing or walking flat.

Our body always has to compensate for gravity (e.g. regulation of blood flow to the upper body). If our head denotes a point in space, then in order to move our head from point 1 (e.g. lying) to point 2 (e.g. standing) we need a certain force, which includes a force of the magnitude of gravity.

The same holds for taking stairs. Head on step 1 is point 1, head on step 2 is point 2, and we need a force to take the difference from point 1 to point 2 plus a force of the magnitude of gravity. This force is bigger than just gravity, so our body needs more "strength" to regulate height differences than just gravity (just standing, walking flat).

Where's the error and what did I forget?
 
Ravn said:
I'm confused about the interplay between chronotropic incompetence - assuming for a moment that we do have it - and POTS?
The first, if I understand correctly, would lead to HR not increasing enough upon exertion.
The second leads to HR increasing too much upon (orthostatic) exertion.
There seems to be a contradiction here?
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My brain is not very sharp right now so apologies that I’m not able to critique the paper specifically. Just wanted to add an anecdote that may illustrate both POTS and chronotropic intolerance (CI) can be present. I had a 2 day CPET that showed “possible” CI and a NASA lean test that met criteria for POTS.

NASA lean test
Baseline supine: HR = 66, BP 125/77
0 minute standing: HR = 70, BP 129/90
10 minute standing: HR = 110, BP 122/93

Generally accepted diagnostic criteria for POTS is a heart rate increase of 30 bpm or more, or over 120 bpm, within the first 10 minutes of standing, in the absence of orthostatic hypotension.

2 day CPET heart rate
Day 1: resting seated = 78, V/AT = 117, peak= 156 (91% of expected)
Day 2: resting seated = 84, V/AT = 102, peak = 140 (82% of expected)

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065291/ (same article linked earlier in this thread): Failure to achieve maximal HR, inadequate submaximal HR, or HR instability during exertion are all examples of impaired chronotropic response.

CI has been most commonly diagnosed when HR fails to reach an arbitrary percentage (either 85%, 80% or less commonly, 70%) of the age-predicated maximal HR (usually based on 220-age equation described earlier) obtained during an incremental dynamic exercise test. CI has also been determined from change in HR from rest to peak exercise during an exercise test, commonly referred to as the HR reserve.
____________________

So my heart rate stays higher than expected with standing, but also on maximal exertion it didn’t reach expected rate. There’s a difference between the exertion and cardiac output required of standing vs maximal exercise.
 
Inara said:
Where's the error and what did I forget?
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POTS is about blood flow based on body orientation. When climbing stairs, the body is not really changing in orientation besides maybe a bit of lean. It is the legs that are doing all the work moving the body against gravity, hence the major difference is simply the metabolic demands of the extra power it takes to walk up stairs.
 
Just putting together my thoughts on this, so apols for slightly random post.

Three early refs mentioned in Davenport's review were the following:

Montague et al. Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest 1989
Riley et al. Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990
Gibson et al. Exercise performance and fatiguability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 1993

All three note blunting of performance or aerobic capacity in the CFS patients they studied, but come to very different conclusions as to why that was.

- Montague: "Patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved. ... Data are compatible with latent viral effects on the cardiac electrical and skeletal muscle tissues."

- Riley: "Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity."

- Gibson: "Patients with chronic fatigue syndrome show normal muscle physiology before and after exercise. Raised perceived exertion scores during exercise suggest that central factors are limiting exercise capacity in these patients."

Reason I mention those three is because they were also mentioned in the Ciba symposium 173 (May 1992) by Edwards, who was the lead investigator on the Gibson paper. His conclusion was that, "On physiological and pathological grounds it is clear that CFS is not a myopathy. Psychological/psychiatric factors appear to be of greater importance in this condition." That must have been all Wessely, White and Sharpe needed to hear to forge forth on their path of destruction. But it was also by influenced and agreed with Lloyd's work in Australia.

This commentary in the BMJ by Thomas in 1993, which seems to summarise the situation after the Ciba symposium, also seems to have 'debunked' any notions that this was a physiological disorder: https://www.bmj.com/content/bmj/306/6892/1557.full.pdf

However, I've also just seen Betsy Keller's NIH presentation, and what was most interesting was her assertion (if I've interpreted it correctly) that the perceived effort noted by patients was not distorted at all, but entirely expected given all the indications of effort and exertion from the data - low blood pressure, inability of heart to properly respond to exertion task to raise blood pressure and heart rate appropriately for the amount of work being done. Her conclusion is that of autonomic dysfunction - not central sensitisation.

 
Hi, have been exploring similar thoughts to Lucibee since Betsy Keller's NIH talk and the slide she showed with the Montague reference.

In the GET therapist manual, P.23, they refer to 8 papers to justify the deconditioning rationale, which also appear in the Davenport tables for single CPET. In the the Davenport paper they are reference numbers 29, 30, 37, 43, 45, 48, 61, 64.

My brain fog is too bad to unpack any detail at the moment. Maybe someone else can...

But grateful to find enough brain function to sign up yesterday after following as a guest for a while. Was grateful for your presence during the recent media storm. Glad to be here.
 
Even Edwards didn't think that it was all due to deconditioning. And although he mentions deconditioning in his Ciba presentation, his published study states: "Patient symptoms in our study cannot be explained by deconditioning though it may contribute to exercise limitation in some CFS patients."

More quotes from the Ciba presentation:
At the end of cycle exercise, CFS patients had a lower peak heart rate (Table 5), a similar finding to that of Montague et al (1989), and reduced lactate levels, suggesting that they were not exercising to their full capacity despite reaching a maximum rate of perceived exertion (RPE) scored on a Borg scale (RPE; Table 5) (Borg 1970).

These data contrast with the findings of Riley et al (1990), who reported a trend towards higher heart rates at rest and a significantly greater heart rate in CFS patients compared to normal subjects and to irritable bowel syndrome controls during submaximal treadmill exercise, but a nonsignificant difference at peak exercise.

Montague et al (1989) attributed their findings in CFS patients to a slow acceleration of heart rate, resulting from a deficit in cardiac pacemaker function or a deficit in sympathetic drive.

Riley et al (1990) attributed their findings to physical deconditioning, with oxygen uptake and lactate levels significantly lower in recovery after exercise, similar to our findings.

‘Deconditioning’ as a result of lack of habitual physical activity reduces exercise capacity (Saltin et al 1968). This is likely to occur in CFS through physical inactivity and may contribute to symptoms, in particular myalgia.
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wrt Perception of effort:
Our findings suggest that CFS patients have a lower threshold for sensation during exercise, or that these patients have an additional burden of ‘fatigue’ at rest over and above that experienced from exercise.
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From the Discussion (with other symposium participants) section:
Edwards: ... we did our muscle testing at intervals from five minutes to 48 hours after exercise in all patients and controls (Gibson et al 1993). We have seen some CFS patients who have had similar exercise tests and say that they were so exhausted, they had to stay in bed for three weeks afterwards. This does not make sense from the physiological point of view.

Straus: You appear to be saying that none of these physiological tests identifies an abnormality that would otherwise not be seen in a physically deconditioned individual? Is that right?

Edwards: Our CFS patients were different from normal controls, never mind deconditioned ones. There is of course a vast range of exercise performance in the normal population (from sedentary individuals to long-distance runners). There is a similarly wide range in CFS patients, from people who have the physiological consequences of being in bed (Saltin et al 1968, Greenleaf & Kozlowski 1982) or in a wheelchair for years, to others who are pottering about yet complaining of fatigue sufficient to fulfil the Oxford consensus criteria for chronic fatigue syndrome (Sharpe et al 1991). So the answer is yes.

Straus: To my mind, you have done a great service to this field in resolving this question.

McCluskey: We have done exercise testing to assess aerobic work capacity in patients with CFS, as you mentioned, and there is no doubt that they are deconditioned. Their heart rate at rest and at submaximal levels of exertion, and the whole-blood lactate levels at submaximal exertion, are significantly higher than those of control subjects or patient control groups. So deconditioning plays some part in the syndrome.
Something that strikes me as important is the way the symptoms fluctuate, from day to day and week to week. There are times when CFS patients can exercise with little fatigue; at other times they are bed-bound. So there is some central mechanism, or something going on centrally, which makes them feel fatigued. This is what we have to try to elucidate.

Edwards: Our observations are very similar on this.

Behan: You don’t know, however, Dr McCluskey, whether their deconditioning is a cause of the results that you and others have found. As yet, nobody has taken deconditioned patients and done those physiological studies on them.

Edwards: Actually, my initial expectation was that these patients would prove to be deconditioned, and I have seen CFS patients who are. It so happened that in this particular age-matched group of 12 young patients they were actually similar to controls. But I know that you, Dr McCluskey, have a group of people who were deconditioned. I don’t see a problem here. There is a selection process, and these patients are not always the same in different places.

Straus: So you are saying, Professor Edwards, that they can be deconditioned and yet have normal muscle physiology, but Professor Behan is saying that they have abnormal muscle?
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Ebb Tide said:
In the GET therapist manual, P.23, they refer to 8 papers to justify the deconditioning rationale, which also appear in the Davenport tables for single CPET. In the the Davenport paper they are reference numbers 29, 30, 37, 43, 45, 48, 61, 64.
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Just unpacking a bit further...

29. De Becker P, Roeykens J, Reynders M, McGregor N, De Meirleir K. Exercise capacity in chronic fatigue syndrome. Arch Intern Med. (2000) 160:3270–77.
"CONCLUSIONS:When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances."

30. Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD. Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc. (2002) 34:51–6.
"CONCLUSIONS: In contrast to most previous reports, the present study found that VO(2max), HR(max), and the LT in CFS patients of both genders were not different from the values expected in healthy sedentary individuals of a similar age."

37. Bazelmans E, Bleijenberg G, Van Der Meer JW, Folgering H. Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychol Med. (2001) 31:107–14.
"CONCLUSIONS: Physical deconditioning does not seem a perpetuating factor in CFS."

43. Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. (2000) 69:302–7.
"CONCLUSIONS: Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function."

45. Gibson H, Carroll N, Clague JE, Edwards RH. Exercise performance and fatiguability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. (1993) 56:993–8.
"Patients with chronic fatigue syndrome show normal muscle physiology before and after exercise. Raised perceived exertion scores during exercise suggest that central factors are limiting exercise capacity in these patients."

48. Inbar O, Dlin R, Rotstein A, Whipp BJ. Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med Sci Sports Exerc. (2001) 33:1463–70.
"these results could indicate either cardiac or peripheral insufficiency embedded in the pathology of CFS patients.
CONCLUSION: We conclude that indexes from cardiopulmonary exercise testing may be used as objective discriminatory indicators for evaluation of patients complaining of chronic fatigue syndrome."

61. Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP. Aerobic work capacity in patients with chronic fatigue syndrome. BMJ. (1990) 301:953–6.
"CONCLUSIONS: Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity."

64. Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, et al. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. (1996) 100:634–40.
"CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness."

Not sure all 8 justify deconditioning. Seems only the Fulcher and White paper does. Quelle surprise!
 
Lucibee said:
wrt Perception of effort:
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Edwards' statement is not consistent with current understanding of effort perception and is inconsistent with the relationship between effort perception and performance at the ventilatory thresholds in more recent 2 day CPET studies...

The equivocal association of deconditioning and performance is exactly that - some patients often are deconditioned compared to their premorbid functioning, but this is not a primary perpetuating cause of continued symptoms or impaired performance. Since some patient still return normal or sometimes even above normal performance on the first day of a 2 day CPET, and as such, deconditioning is neither a sensitive nor specific predictor of symptoms or illness severity.
 
Lucibee said:
Just unpacking a bit further...

29. De Becker P, Roeykens J, Reynders M, McGregor N, De Meirleir K. Exercise capacity in chronic fatigue syndrome. Arch Intern Med. (2000) 160:3270–77.
"CONCLUSIONS:When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances."

30. Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD. Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc. (2002) 34:51–6.
"CONCLUSIONS: In contrast to most previous reports, the present study found that VO(2max), HR(max), and the LT in CFS patients of both genders were not different from the values expected in healthy sedentary individuals of a similar age."

37. Bazelmans E, Bleijenberg G, Van Der Meer JW, Folgering H. Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychol Med. (2001) 31:107–14.
"CONCLUSIONS: Physical deconditioning does not seem a perpetuating factor in CFS."

43. Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. (2000) 69:302–7.
"CONCLUSIONS: Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function."

45. Gibson H, Carroll N, Clague JE, Edwards RH. Exercise performance and fatiguability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. (1993) 56:993–8.
"Patients with chronic fatigue syndrome show normal muscle physiology before and after exercise. Raised perceived exertion scores during exercise suggest that central factors are limiting exercise capacity in these patients."

48. Inbar O, Dlin R, Rotstein A, Whipp BJ. Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med Sci Sports Exerc. (2001) 33:1463–70.
"these results could indicate either cardiac or peripheral insufficiency embedded in the pathology of CFS patients.
CONCLUSION: We conclude that indexes from cardiopulmonary exercise testing may be used as objective discriminatory indicators for evaluation of patients complaining of chronic fatigue syndrome."

61. Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP. Aerobic work capacity in patients with chronic fatigue syndrome. BMJ. (1990) 301:953–6.
"CONCLUSIONS: Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity."

64. Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, et al. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. (1996) 100:634–40.
"CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness."

Not sure all 8 justify deconditioning. Seems only the Fulcher and White paper does. Quelle surprise!
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All of these discussions about deconditioning completely avoid the fluctuating course of the disease, not only long-term but shockingly short-term. There is no such thing as fluctuating deconditioning, an otherwise healthy person cannot be deconditioned in the morning but not in the afternoon, or any variation of this. Some patients experience a very rapid deterioration, within days, into a severe state, for which a deconditioning hypothesis makes no sense.

This decades-long discussion makes me think of people puzzling for years over why a machine does not work, completely ignoring the passersby pointing out that it isn't even plugged in. There can be many explanations but deconditioning is one that should have been discarded at step 1. Science without common sense can be so damn stupid sometimes.
 
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