Review: Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome. Nelson et al. 2019

[John Mac]

Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome
A systematic review and meta-analysis

Nelson, Maximillian J. PhDa,∗; Bahl, Jasvir S. BAppScia; Buckley, Jonathan D. PhDa; Thomson, Rebecca L. PhDa,b; Davison, Kade PhDa

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition with no reliable diagnostic biomarkers. Studies have shown evidence of autonomic dysfunction in patients with ME/CFS, but results have been equivocal. Heart rate (HR) parameters can reflect changes in autonomic function in healthy individuals; however, this has not been thoroughly evaluated in ME/CFS.

Methods: A systematic database search for case-control literature was performed. Meta-analysis was performed to determine differences in HR parameters between ME/CFS patients and controls.

Results: Sixty-four articles were included in the systematic review. HR parameters assessed in ME/CFS patients and controls were grouped into ten categories:
resting HR (RHR),
maximal HR (HRmax),
HR during submaximal exercise,
HR response to head-up tilt testing (HRtilt),
resting HR variability (HRVrest),
HR variability during head-up tilt testing (HRVtilt),
orthostatic HR response (HROR),
HR during mental task(s) (HRmentaltask),
daily average HR (HRdailyaverage),
and HR recovery (HRR)

Meta-analysis revealed
RHR (MD ± 95% CI = 4.14 ± 1.38, P < .001),
HRtilt (SMD ± 95% CI = 0.92 ± 0.24, P < .001),
HROR (0.50 ± 0.27, P < .001),
and the ratio of low frequency power to high frequency power of HRVrest (0.39 ± 0.22, P < .001) were higher in ME/CFS patients compared to controls,
while HRmax (MD ± 95% CI = –13.81 ± 4.15, P < .001),
HR at anaerobic threshold (SMD ± 95% CI = –0.44 ± 0.30, P = 0.005) and the high frequency portion of HRVrest (–0.34 ± 0.22, P = .002) were lower in ME/CFS patients.

Conclusions: The differences in HR parameters identified by the meta-analysis indicate that ME/CFS patients have altered autonomic cardiac regulation when compared to healthy controls. These alterations in HR parameters may be symptomatic of the condition.

https://journals.lww.com/md-journal..._altered_cardiac_autonomic_regulation.36.aspx

 

[DokaGirl]

Thank you for posting this @John Mac.

Great to see the review - at long last.

PwME, knowledgeable clinicians and ME researchers have known for decades we have autonomic cardiac problems.

Most others seem to have dismissed this.

I note the authors didn't include: https://www.amjmedsci.com/article/S0002-9629(15)34232-4/abstract in their reference list.

 

[Snow Leopard]

None of these findings are a smoking gun (and there are few questionable statements in the review), but it does suggest a particular hypothesis should be ruled out...

Interestingly, of the studies which reported maximal HR in ME/CFS patients, the majority that also reported VO2max (10 of 17) found a lower VO2max in ME/CFS patients compared to controls, which could suggest that deconditioning is common in ME/CFS. However, of these studies, four of them were those which used a criterion approach to determine if a valid maximal effort had been given, and these studies found no difference in VO2max between ME/CFS and controls, implying that many ME/CFS patients may not be deconditioned compared to controls, but are unable to produce a valid voluntary maximal effort, possibly due to kinesiophobia.

This mention of kinesiophobia is total nonsense as these are patients who agreed to participate in a maximal CPET study. There may be a few patients with kinesiophobia, but those patients would refuse to participate in a study like this by definition.

In addition to ME/CFS patients having a higher RHR, they exhibited differences in HRVrest that also suggest the presence of reduced parasympathetic and increased sympathetic cardiac autonomic modulation. ME/CFS patients had lower HFP and RMSSD, with both parameters representing primarily parasympathetic cardiac modulation.[92,93] ME/CFS patients also had a higher LF/HF ratio than controls, indicating increased sympathetic and decreased parasympathetic HR modulation compared to controls.[94] The effect sizes for the differences between ME/CFS patients and controls were consistently small (albeit significant), and this may explain why no significant effect was found for other HRVrest parameters which had fewer included studies. LFP, for example, reflects a combination of parasympathetic and sympathetic modulation of HR vagal cardiac modulation in a similar manner to HFP, however the small number of included studies for this parameter may limited the ability for the current meta-analysis to identify a significant effect.

They claim the presence of 'increased sympathetic cardiac autonomic modulation' (during rest), yet the meta analysis found no difference in low frequency power (LFP), but did find a decrease in high frequency power (HFP). Notably, one of the studies that found an increase in LFP also found a increase in HFP. Hence the difference in LF/HF ratio is likely due to lowered parasympathetic activity, rather than increased sympathetic activity, which rules out Wyller's "Sustained arousal" hypothesis. Secondly, Light et al.'s post exercise gene expression studies found an increase in genes for beta-adrenergic receptors suggesting blunted post-exercise parasympathetic activity.

Of course most of these findings can simply be explained by deconditioning, though there remains the possibility of a minority of patients with a POTS type condition that may explain their symptoms.

The authors state.

LaManca et al[50] measured stroke volume during HUTT in ME/CFS patients, and found stroke volume decreased in a similar manner to that seen in other deconditioned populations,[112] and suggested the increased HRtilt witnessed during that study attempted to counteract a hypovolaemic state which had led to decreased preload and decreased stroke volume. Similar observations have been made by other studies in ME/CFS populations.[43,66]

Which seems reasonable to me...

 

[lansbergen]

This mention of kinesiophobia is total nonsense as these are patients who agreed to participate in a maximal CPET study. There may be a few patients with kinesiophobia, but those patients would refuse to participate in a study like this by definition.

Yep

 

[NelliePledge]

Yes- apologies all but kinesiophobia my arse - might as well go the whole hog and say catastrophising, fear avoidance and all the other BS terms Chalder & co use. Just imagine them reading this paper -literally the only thing they would register is that mention of kinesiophobia.

 

[rvallee]

Yep

When all it takes is basic common sense to discredit a theory...

 

[Ravn]

Yes- apologies all but kinesiophobia my arse - might as well go the whole hog and say catastrophising, fear avoidance and all the other BS terms Chalder & co use. Just imagine them reading this paper -literally the only thing they would register is that mention of kinesiophobia.

They do (my bolding).

As ME/CFS patients (similarly to most chronic health conditions) have been shown to catastrophize their symptoms of pain, leading to a negative effect on exercise performance,[102] the use of regular verbal encouragement during maximal exercise tests in ME/CFS may be particularly important in order to elicit a valid maximal response in this population.

reducing the capacity for participation in physical activity which may be further compounded by active avoidance of activity even when able, for fear of inducing post-exertional malaise and severe exacerbation of symptoms.

In fairness, they do conclude:

that deconditioning cannot explain all of the variance in HR parameters between ME/CFS patients and controls. Rather, it is likely that an altered cardiac autonomic balance is present in ME/CFS patients, typified by increased sympathetic and decreased parasympathetic cardiac autonomic control.

 

[NelliePledge]

Oh great

 

[rvallee]

They do (my bolding).



In fairness, they do conclude:

I will forever be puzzled at how smart people are so confused by the simple fact that people who have previously touched a very hot stove are motivated by not touching the very hot stove again and insist that people should instead be motivated at touching the very hot stove.

False attribution errors are so cheap and stupid.

 

[Sean]

False attribution errors are so cheap and stupid.

But very convenient, for some.

 

[Kitty]

Well, at least we'll all know when science does finally catch up with ME. The studies will all be blaming patients for making themselves worse by pig-headedly doing stuff they know they probably shouldn't.