Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome, Roerink et al. 2016

[Evergreen]

Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome​

M. E. Roerink, J. W. M. Lenders, I. C. Schmits, A. M. A. Pistorius, J. W. Smit, H. Knoop, J. W. M. van der Meer
First published: 02 October 2016

https://doi.org/10.1111/joim.12564

Abstract​

Background​

Postural orthostatic tachycardia syndrome (POTS) is considered a diagnostic marker for chronic fatigue syndrome (CFS).

Objectives​

The aims of this study were to (i) compare POTS prevalence in a CFS cohort with fatigued patients not meeting CFS criteria, and (ii) assess activity, impairment and response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS-CFS) and without POTS (non-POTS-CFS).

Methods​

Prospective cohort study at the Radboud University Medical Centre in the Netherlands. Between June 2013 and December 2014, 863 consecutive patients with persistent fatigue were screened. Patients underwent an active standing test, filled out questionnaires and wore an activity-sensing device for a period of 12 days.

Results​

A total of 419 patients with CFS and 341 non-CFS fatigued patients were included in the study. POTS prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P = 0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P = 0.93). Adult patients with POTS-CFS were younger (30 ± 12 vs. 40 ± 13 years, P = 0.001) and had a higher supine heart rate (71 ± 11 vs. 65 ± 9 beats per min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity patterns did not differ between groups. In patients with CFS, criteria for Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of adolescents. In these patients with CFS fulfilling the SEID criteria, the prevalence of POTS was not different from that in the overall CFS population. POTS-CFS adolescents had less clinically significant improvement after CBT than non-POTS-CFS adolescents (58% vs. 88%, P = 0.017).

Conclusion​

In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

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[Evergreen]

Here's another study relevant to prevalence of POTS in CFS.

It was done on consecutive patients presenting to a specialist service. This service does not have a special interest in POTS or orthostatic intolerance. It's a CBT service.

They used active stand rather than head-up tilt to provoke and define POTS:

POTS was defined as an increase in heart rate of at least 30 bpm compared to the supine position, or a standing heart rate of ≥120 bpm for any of the measurements within the first 10 min after attaining an upright position

This is the conclusion of the abstract:

In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

This is the nitty-gritty:

POTS prevalence in CFS, SEID and non-CFS patients​

The prevalence of POTS was 8.4% (35/419) within the total CFS population, and 5.7% for adults (19/331) and 18.2% for adolescents (16/88). The POTS prevalence was not different between patients with (BDI ≥4) and without a clinically significant level of depressive symptoms (5.8% vs. 5.7%, P = 0.96). In patients with CFS fulfilling the SEID criteria, POTS was present in 5.2% of adults (13/251) and 22.0% of adolescents (13/59), which was not significantly different from the POTS prevalence in the overall CFS population (P = 0.77 and P = 0.57, respectively). In the non-CFS fatigued population, POTS was present in 6.9% (22/318) of adults and 17.4% (4/23) of adolescents, which was not statistically different from patients with CFS (P = 0.54 and P = 0.93, respectively).

Response to CBT:

Amongst adults, POTS-CFS and non-POTS-CFS patients responded similarly to CBT. However, fewer adolescents with POTS-CFS recovered after CBT compared with non-POTS-CFS patients (58% vs. 88%, P = 0.017).

Bottom line:

In this study, the prevalence of POTS in a large CFS cohort of adults and adolescents was 5.7% and 18.2%, respectively, which is much lower than the 27% reported in the review by the IOM. POTS prevalence was not different in patients with CFS who fulfilled the SEID criteria.

 

[Evergreen]

See also my post here on a few studies by Newton's team on the prevalence of POTS in (ME/)CFS.

 

[Turtle]

Would have been nice if the authors had some knowledge about POTS.
Doing the blood pressure measurement 5 to 8 minutes into the standing test.
They missed the most important timeslot at the beginning of the standing test.
No wonder prevalence was low.
Standing test only. No tilt table test and the use of a doppler was not yet known.
The recovery rate after CBT is staggering.

 

[Evergreen]

The key difference between this study and others is that people with CFS (Fukuda) are being compared with people with chronic fatigue who did not meet Fukuda criteria, rather than healthy controls.

Just wanted to highlight that.

 

[Evergreen]

Doing the blood pressure measurement 5 to 8 minutes into the standing test.
They missed the most important timeslot at the beginning of the standing test.

I think you're right to look carefully at how they defined POTS. But they weren't trying to capture changes in blood pressure, they were trying to capture changes in heart rate. To be considered POTS, blood pressure needs to remain stable:

Only patients without signs of orthostatic hypotension within the first 10 min, defined as a decrease in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg, could be identified as having POTS.

It's actually unclear to me from the text exactly when they measured heart rate. But we know they measured it a number of times in the 10 mins after standing. And to be considered POTS, the heart rate has to stay up. So even if they missed that it shot up at 2 mins, it would still have been up on the later measurements if the person had POTS.

 

[Evergreen]

The recovery rate after CBT is staggering.

Isn't it? 88%. As if.

 

[InitialConditions]

To be considered POTS, blood pressure needs to remain stable:

Ok, but that means you have to measure blood pressure, which it sounds like they didn't do for half the test.

Active stand rather than TTT will likely explain the low POTS rates.

I don't trust anyting from Knoop + co having looked into some of his work.

 

[Evergreen]

Active stand rather than TTT will likely explain the low POTS rates

There will definitely be more postural tachy detected on tilt because it removes your ability to use your legs. But whether tilt is more accurate than active stand is debatable. Active stand is more like real life.

I don't trust anyting from Knoop + co having looked into some of his work.

Yes, they have been prominent in BPS/CBT. But we have to be just as sceptical of work that comes up with daft proportions of pwME/CFS having X, Y or Z.

What proportion of pwME/CFS do we think have POTS?

Oh wow, here's what AI says:

Studies estimate that approximately 25% to 50% of people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) also have Postural Orthostatic Tachycardia Syndrome (POTS), a form of autonomic dysfunction (dysautonomia). Prevalence estimates for POTS in the ME/CFS population vary widely, with reports ranging from 6% to as high as 70% in certain studies.

I don't thnk 25-50% of pwME/CFS have POTS.

 

[InitialConditions]

Oh wow, here's what AI says:
I don't thnk 25-50% of pwME/CFS have POTS.

This survey estimated 27%: https://meassociation.org.uk/2023/1...hostatic-tachycardia-syndrome-survey-results/

 

[Evergreen]

This survey estimated 27%: https://meassociation.org.uk/2023/1...hostatic-tachycardia-syndrome-survey-results/

Yes, and the methodology is exactly why they got 27% - similar to the 29% Newton's group found when they recruited patients in a similar way. But when Newton's group came back with better methodology - consecutive patients - that figure went down to 13%, and that was in a centre which would have attracted more patients with orthostatic intolerance and POTS because they had a special interest in it that was well-known. Note the jump from 2.5% to 13% in a few years at the service - at least some of that will be because of that special interest:

In Hoad et al. 2008 Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome, participants were selected like this:
and they found 29% had POTS.

In a study of their own service, 2.5% (4/157) of those referred and diagnosed with CFS 2008-2009 were found to have POTS. I note that 20% were reported to have CFS "precipitated by an infective episode" which seems unusually low.

The team came back in 2012 and did another study, Lewis et al. 2012 Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatictachycardia syndrome, where patients were selected like this:
and they found 13% had POTS.

Newton's team's interest in POTS, and orthostatic intolerance more generally, was big news in the UK ME/CFS world at the time. So the 13% is likely to be inflated by selection bias.

The same has been claimed about Sjögren's. The numbers shrink when the methodology improves.

As a reminder, the Nishikai and Sirois studies reported 29%-32% of CFS patients met 1993 diagnostic criteria for Primary Sjögren's Syndrome. Now we’re down to less than 7% on 2002 criteria in a cohort we’d expect to be biased towards Sjögren's, and some fraction of 3.5% in a cohort we’d expect to be less biased.

@ME/CFS Science Blog has a table summarising prevalence of POTS in ME/CFS studies in their blog.

 

[InitialConditions]

@ME/CFS Science Blog has a table summarising prevalence of POTS in ME/CFS studies in their blog.

Yes, I remember now. OI comon in ME/CFS but it's not always PoTS.

 

[Evergreen]

This is incredible, from Lee et al. 2020 (including Vernon, Bateman) which used the NASA lean test:

OH was defined as a decrease in SBP of 20 mm Hg or more, or a decrease in DBP of 10 mm Hg or more in the first 3 min standing compared to resting supine values.

POTS was defined as an increase of HR greater than 30 bpm or a HR of greater than 120 bpm, based on the average of the last three minutes standing. (e.g., if the standing portion of the test was terminated at 6 min, we calculated the mean of the data recorded during the 3rd, 4th and 5th minutes).

The 10-minute NLT induced OI manifestations of POTS and OH in 54% of ME/CFS participants and 49% of HCs (Table 2).

Further, HR increased in all groups for each minute of standing so that by 10 min 33% of HCs, 42% < 4 MECFS and 38% > 10 MECFS met POTS criteria. [<4 years and >10 years duration of illness]

Now, 33% of healthy controls do not have debilitating tachycardia on standing that should be treated. They just don't. That would suggest that most of those with ME/CFS meeting POTS criteria might not either.

Where the groups did differ was in symptoms: people with ME/CFS felt a lot worse than healthy controls when standing.

 

[rvallee]

Here's another study relevant to prevalence of POTS in CFS.

It was done on consecutive patients presenting to a specialist service. This service does not have a special interest in POTS or orthostatic intolerance. It's a CBT service.

I can't really see studies like this as useful because there is too much selection effect. Almost all relevant services exclude severe patients and would make no accommodations for them, so they will never see those cases. They exclusively focus on the mildest cases because it gets them the same overall effect as potato socks during a cold: free/fake success. Put a potato in your socks, and bam!, a few days later no cold. Mind-body-potato for the win!

When I had POTS 3 years ago, meeting those criteria, you would never have seen me in such a clinic, I was way too impaired. Especially with the knowledge I already had of how poorly we get treated, there is no way I would have been considered it worth it. When people are very ill and have to go through difficult treatments or processes, they do it because they think it's worth it. Why would anyone so impaired think it would be worth going to such a clinic? Even in the best case, there is every expectation that it would be wasted.

Similar reason why most clinicians who work at such services constantly minimize severe ME, generally don't even think it exists: they exclude them, and so never see them. Out of sight, on purpose, out of mind, on purpose.

 

[Evergreen]

When I had POTS 3 years ago, meeting those criteria, you would never have seen me in such a clinic, I was way too impaired. Especially with the knowledge I already had of how poorly we get treated, there is no way I would have been considered it worth it. When people are very ill and have to go through difficult treatments or processes, they do it because they think it's worth it. Why would anyone so impaired think it would be worth going to such a clinic? Even in the best case, there is every expectation that it would be wasted.

Yes, you make a good point - but you may not be typical. I think many people would seek help when very symptomatic with POTS because it's just so debilitating. Plenty of people would expect to get help for POTS, because it's presented as one of the few things that's treatable.

 

[Evergreen]

This is from Raj 2006, which as far as I can gather is considered an/the ur-text on POTS:

POTS is defined (Table 1) as the presence of symptoms of orthostatic intolerance for at least 6 months accompanied by a heart rate increase of at least 30 beats/min within 5-30 minutes of assuming an upright posture. This should occur in the absence of orthostatic hypotension (a fall in blood pressure >20/10 mmHg). The syndrome must occur in the absence of prolonged bed rest, medications that impair autonomic regulation (such as vasodilators, diuretics, antidepressants or anxiolytic agents), or any other chronic debilitating disorders that might cause tachycardia (such as dehydration, anemia or hyperthyroidism). It is important to recognize that this syndrome is typically disabling. Hence, the mere observation of orthostatic tachycardia is not, by itself, sufficient to make the diagnosis of POTS.

That would cut a lot of people with ME/CFS out of contention.

 

[Felis Catus]

Yes, you make a good point - but you may not be typical. I think many people would seek help when very symptomatic with POTS because it's just so debilitating. Plenty of people would expect to get help for POTS, because it's presented as one of the few things that's treatable.

It might depend on the location.

My GP acknowledged the possibility of POTS raised by a private doctor but said there were no POTS specialists in the area to refer me to. Case closed.

I've heard of local people going to the nearest major city for private appointments but that's at least 2h of door-to-door travel in one direction. Some cardiologists do remote online appointments but privately. PoTS UK website doesn't list any NHS specialists in my ICB area. I guess we could still be referred to a cardiologist but... well, I wasn't.