Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS, 2023, van Campen et al.

[SNT Gatchaman]

Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS
van Campen; Verheugt; Rowe; Visser

Background:
Orthostatic intolerance (OI) is a core diagnostic criterion in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). The majority of ME/CFS patients have no evidence of hypotension or postural orthostatic tachycardia syndrome (POTS) during head-up tilt, but do show a significantly larger reduction in stroke volume index (SVI) when upright compared to controls. Theoretically a reduction in SVI should be accompanied by a compensatory increase in heart rate (HR). When there is an incomplete compensatory increase in HR, this is considered chronotropic incompetence. This study explored the relationship between HR and SVI to determine whether chronotropic incompetence was present during tilt testing in ME/CFS patients.

Methods:
From a database of individuals who had undergone tilt testing with Doppler measurements for SVI both supine and end-tilt, we selected ME/CFS patients and healthy controls (HC) who had no evidence of POTS or hypotension during the test. To determine the relation between the HR increase and SVI decrease during the tilt test in patients, we calculated the 95% prediction intervals of this relation in HC. Chronotropic incompetence in patients was defined as a HR increase below the lower limit of the 95 th % prediction interval of the HR increase in HC.

Results:
We compared 362 ME/CFS patients with 52 HC. At end-tilt, tilt lasting for 15 (4) min, ME/CFS patients had a significantly lower SVI (22 (4) vs. 27 (4) ml/m2 ; p<0.0001) and a higher HR (87 (11) vs. 78 (15) bpm; p<0.0001) compared to HC. There was a similar relationship between HR and SVI between ME/CFS patients and HC in the supine position. During tilt ME/CFS patients had a lower HR for a given SVI; 37% had an inadequate HR increase. Chronotropic incompetence was more common in more severely affected ME/CFS patients.

Conclusion:
These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing in ME/CFS patients.

Link | PDF (IBRO Neuroscience Reports)

 

[SNT Gatchaman]

Highlights:

• Adults with ME/CFS experience a 3-fold greater reduction in cerebral blood flow during endtilt tilt compared to healthy controls, confirming orthostatic intolerance.
• During tilt testing we found that in 134/362 (37%) patients with ME/CFS without POTS or hypotension, the heart rate increase was below the lower limit of the 95% prediction interval of the heart rate increase of controls, indicative of orthostatic chronotropic incompetence.
• These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing, confirming another abnormality in the circulatory response to upright posture in ME/CFS.

 

[Sid]

So much for anxiety about standing.

 

[Andy]

"During the first visit, we determined by history taking of the treating physician whether patients satisfied the criteria for CFS (Fukuda et al., 1994) and ME (Carruthers et al., 2011), taking the exclusion criteria into account. "

"All patients fulfilled the CFS criteria and 261 had typical ME (72%), 101 (28%) had atypical ME. "

 

[Ravn]

"All patients fulfilled the CFS criteria and 261 had typical ME (72%), 101 (28%) had atypical ME. "

Huh?

Haven't read the paper but a word search for typical & atypical didn't bring up any definitions. Have the authors defined 'atypical ME' elsewhere?

 

[Hoopoe]

If I remember right atypical ME in the context of the Canadian criteria means no infectious onset.

 

[Andy]

Have the authors defined 'atypical ME' elsewhere?

Nope, not that I could find.

However, "All patients fulfilled the CFS criteria and 261 had typical ME (72%), 101 (28%) had atypical ME."; I understand that to mean that 261 (72%) met the ICC and that the balance has atypical ME, which is just those who only met Fukuda, which they describe as the "CFS" criteria...

If I remember right atypical ME in the context of the Canadian criteria means no infectious onset.

I just checked and couldn't find any reference in the CCC to "atypical" ME.

 

[cassava7]

“Atypical” ME is an oddity of the international consensus criteria, which define it as: “meets criteria for postexertional neuroimmune exhaustion but has a limit of two less than required of the remaining criterial symptoms. Pain or sleep disturbance may be absent in rare cases.”

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2011.02428.x (see Table 1)

 

[SNT Gatchaman]

Cross-posting with @cassava7

This left 362 ME/CFS patients (55 male, 307 female) with no evidence of POTS or hypotension on tilt testing for analysis.

All patients fulfilled the CFS criteria and 261 had typical ME (72%), 101 (28%) had atypical ME. Using the ICC definition of disease severity, 117 patients were graded as having mild, 198 patients as moderate and 47 patients as severe ME/CFS.

To classify ME/CFS severity, we used the ICC criteria. Mild severity required an approximate 50% reduction in pre-illness activity level. Moderate severity required patients to be mostly housebound. Severe patients were mostly bedridden and very severe patients were totally bedridden and needed help with basic functions. Very severe patients were excluded because they were unable to tolerate tilt testing.

261 + 101 = 362
117 + 198 + 47 = 362

So I read as all fulfilled "CFS" (Fukuda). All fulfilled ICC for either typical or atypical.

261/362 were typical (ie PENE + 3 neuro symptoms + 3 immune/gastro/genitourinary symptoms + 1 cardiovascular symptom)
101/362 were atypical (ie PENE + 1 neuro symptom + 1 immune/gastro/genitourinary symptom).

 

[Mij]

If I remember right atypical ME in the context of the Canadian criteria means no infectious onset.

I don't think so. The M.E specialist I saw who co-authored the Canadian criteria diagnosed me with 'atypical' M.E. I had a sudden viral infectious onset, but in the early years I didn't have OI, insomnia, cognitive issues or pain. There was no definition for PEM back then and was never mentioned. I didn't have PEM as far as I knew back then either.

I was eventually diagnosed after r./o MS and having a relapse from returning to work.

 

[John Mac]

It would have been interesting to know what would have happened if they had included sedentary controls as well as healthy controls i.e. cause versus effect.

 

[ME/CFS Skeptic]

It would have been interesting to know what would have happened if they had included sedentary controls as well as healthy controls i.e. cause versus effect.

Yes there were also reports of chronotropic intolerance in exercise tests of ME/CFS but those seem to disappear when controls were matched for fitness. So I wonder if the results in this paper may simply be due to deconditioning/the ME/CFS patients being less fit than the controls.