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

Ravn

Ravn

Senior Member (Voting Rights)
Provisionally accepted 26 Feb 2019, full text soon

Chronotropic incompetence: an overlooked determinant of symptoms and activity limitation in myalgic encephalomyelitis/chronic fatigue syndrome?
Davenport et al
Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM. In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS. Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor. In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship. However, s maller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic incompetence (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate. The purposes of this review are to (1) define CI and discuss its applications to clinical populations; (2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and (3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice.
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https://www.frontiersin.org/articles/10.3389/fped.2019.00082/abstract
 
Broken up for easier reading:

Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion.

Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM. In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS.

Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor.

In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship.

However, smaller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic incompetence (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate.

The purposes of this review are to

(1) define CI and discuss its applications to clinical populations;

(2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and

(3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice.​
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I wonder what spiritual over-exertion is.

Given that this is a plan for a systematic review of existing studies, this suggests there is evidence already in published papers of chronotropic incompetence in pwME. I wonder if anyone can point us to such studies. I'm curious.

Edited to add 'plan for a'

Second edit: I see it's the Workwell people. That's good, it means they have access to their own raw data.
 
Trish said:
Given that this is a plan for a systematic review of existing studies, this suggests there is evidence already in published papers of chronotropic incompetence in pwME. I wonder if anyone can point us to such studies.
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It's something that was noted in most of the regular (single day) exercise studies. I wondered what's it's about and why nobody was writing about it. One of the largest 1 day CPET studies for examples wrote:
"The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. [...] It is a peculiar finding that, although most of our patients reached the respiratory anaerobic threshold, far fewer of them also reached their THR. This would also indicate that suboptimal cardiac function is a major limiting factor in exercise capacity in patients with CFS."
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There is a section about this on the MEpedia PEM page. It provides references and reads:
A Canadian team under the guidance of Terrence Montague noted that during a maximal exercise test, ME/CFS patients have a lower maximal heart rate than controls. The authors noted that:“...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.”[113]A significantly lower peak heart rate has been repeatedly observed in CPET-studies with ME/CFS patients.[114][115][116] In one of the largest of these into exercise performance, the authors noted the same phenomenon as Montague et al.“The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects.”
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Cook et al. (2003), the research team of Benjamin Natelson, even suggested that this indicates that HR may not be the most adequate physiological measure to prevent PEM.
our CFS subjects had significantly lower peak heart rates. Thus, heart rate may not be a good indicator of exertion in the CFS patient.
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This was all a long time ago. Don't know why these findings weren't followed up on. Will be interesting to read what the Workwell Foundation team has to say about this...
 
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I'll comment again in more depth when I've read the full paper, but I think this paper is barking up the wrong tree for most patients (there are other reasons for the lower HR peak). But it is equally disappointing that researchers have been mentioned chronotropic incompetence for years, but no one has actually bothered to measured EMG signalling and whether there is increased latency of HR rise or reduced rate of increase.
Simply finding patients HR didn't reach predicted norms is insufficient since there are a wide variety of reasons for this, beyond being limited by insufficient sympathetic drive.

There is a paper that will hopefully be published soon which examined rate of change of heart rate rises/reductions/recovery associated with the 2 day CPET and the results were normal.

That said, in a small minority of patients, there may be specific disease (particularly genetic issues) causing chronotropic incompetence and this needs to be diagnosed...

Oh and some additional reading while you wait:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065291/
 
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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?
 
When I started wearing a heart rate monitor I was amazed to see that my heart rate was higher at those times I felt I had to lie down since there had never been any physical test that matched what I felt.

On a usual day my HR is about 85 to 90 at rest down to about 75 when lying down motionless and up to 105 when I am doing something. However I have found from experience that if I am experiencing a crash my HR goes down to the 60's or even 50's if it is bad. I assume it is because I do not have the energy available to speed up my heart.

My blood pressure also does strange things.

Over the past few years my symptoms vary but I have episodes of severe POTS, particularly in hot weather where my heart rate goes up to 150 when I am upright, with all the vertigo, nausea and so on associated with it.

I think that we may have a secondary POTS which could be different from normal, more associated with a malfunctioning hypothalamus. With ME I believe the availability of ATP at any given moment determines how well every system works. It would explain why everything is normal when tested but then doesn't work when it is needed.
 
Before CFS the basal ganglia and the hypothalamus were implicated in ME. The lack of homeostasis was seen as being an important symptom with temperature regulation and so on being very bad for most people. I always thought that POTS is a form of this but I am not very knowledgeable about the science.
 
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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Check my conversation with Todd Davenport:

 
Snow Leopard said:
it is equally disappointing that researchers have been mentioned chronotropic incompetence for years, but no one has actually bothered to measured EMG signalling and whether there is increased latency of HR rise or reduced rate of increase.
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I'm very curious- what could be determined if EMG signalling is measured? On which nerve(s) would the EMG be conducted?

What would an increased latency or reduced rate of HR rise indicate?

If you’ve addressed this elsewhere, just point me in the right direction...

ETA:
Ok, I have gone back and read some of your previous posts, @Snow Leopard .

Do you think the lowered HR increase is secondary to impaired muscle tissue metabolism, perhaps by dysautonomic failure to recruit sufficient muscle fibers or perhaps by dysautonomic failure to dilate the arterioles supplying the muscle fibers with oxygen?
 
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I'm confused by that graph:

HR-graph-3-330x271.png


Why aren't PWME's heart rates going about 60 bpm? I thought our problem was struggling to keep our HRs below our aerobic (or something) thresholds?
 
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