Featured Research

ME/CFS, Orthostatic Intolerance, and the Tilt Table Test

Background

Individuals with ME/CFS often report experiencing orthostatic intolerance – symptoms, such as light-headedness and feeling weak, when sitting- or standing up, leading to difficulty tolerating an upright posture. These symptoms are relieved by lying down. Orthostatic intolerance is thought to occur as a result of abnormal blood flow to the brain.

Postural orthostatic tachycardia syndrome (PoTS) is a condition that is characterised by orthostatic intolerance, including a hallmark persistent tachycardia (increased heart rate) upon assuming an upright posture. The tilt table test – the gold standard test for PoTS – involves a person’s heart rate (HR) and blood pressure (BP) being monitored whilst they are strapped to a special table which gradually tilts from flat to upright. Whilst PoTS is a known comorbidity of ME/CFS, many people with ME/CFS do not have the abnormal heart rate-blood pressure (HR-BP) response required for a PoTS diagnosis, despite being impacted by orthostatic intolerance. This could potentially lead to these individuals being overlooked for further investigation and management advice.

Abnormal body responses in ME/CFS without PoTS

A research team, who are predominantly based in the Netherlands, showed that most participants with ME/CFS and normal HR-BP response (i.e. no PoTS) during tilt table testing had other physiological abnormalities occurring during assessment. Specifically, in comparison to healthy controls, cardiac output (how much blood heart pumps) and cerebral blood flow ( how much blood brain receives) were abnormally reduced during the tilt. Cardiac output and cerebral blood flow are not always included in routine tilt table testing.

Analysing the data patterns, the researchers suggested that the results indicated an “absence of compensatory vasodilation in the cerebral vasculature” i.e. blood vessels in the brain are not reacting appropriately to a change in body position. This could be an indicator of endothelial dysfunction – when the lining of blood vessels (endothelium) does not work properly.

The study – in more depth

What was the aim of the study?

The goal was “to test the relationship between [cerebral blood flow] and [cardiac output], which seems to be abnormal in ME/CFS patients and is different from that in [healthy controls].” Orthostatic intolerance is thought to be a consequence of abnormal cerebral blood flow, and according to the researchers – cardiac output “is an important determinant” of cerebral blood flow.

What was involved in the study?

The researchers analysed the medical records of individuals with ME/CFS who underwent tilt table testing between October 2012 and May 2022 at an outpatient clinic and also had data available for cardiac output and cerebral blood flow. Subject to exclusion criteria, they selected individuals with ME/CFS who had a normal HR-BP response (i.e. those with ME/CFS who don’t meet the diagnostic criteria for PoTS) for further analysis. 534 individuals with ME/CFS were included and compared with 49 healthy controls (who also had cerebral blood flow and cardiac output measurements available).

What did they find?

91% of individuals with ME/CFS (and no PoTS diagnosis) had an abnormal cerebral blood flow and cardiac output reduction during the tilt table test. Specifically in this group, cerebral blood flow and cardiac output had an almost 1:1 relationship in terms of percentage reduction. The researchers suggest this pattern most likely indicates endothelial dysfunction of blood vessels in the brain is contributing to abnormal cerebral blood flow regulation during “orthostatic stress” (the strain on the body whilst going from lying to upright).

Limitations

The researchers acknowledge several limitations which could impact on the generalisability of findings, including the fact that the study “is retrospective and referral bias by the general practitioner may have played a role, selectively referring patients with orthostatic symptoms.” However, they mention that this would not have interfered with the relationships observed between cerebral blood flow and cardiac output.

Discussion

Abnormal cerebral blood flow is an indicator of orthostatic intolerance. Many individuals with ME/CFS have orthostatic intolerance, but not PoTS –  a condition that is characterised by orthostatic intolerance but specifically includes an abnormal rise in heart rate upon assuming an upright posture. During tilt table testing (gold standard test for PoTS), cerebral blood flow and the related cardiac output are not routinely measured. This study showed that the majority of individuals with ME/CFS, without PoTS, demonstrated abnormal reductions in cerebral blood flow and cardiac output on tilt table testing. Furthermore, the researchers suggested that the data patterns in this group indicated endothelial dysfunction.

These findings reinforce that many individuals with ME/CFS who do not have PoTS, have orthostatic intolerance. Based on the findings the researchers propose that “circulatory improvement by increased water and salt intake, compression garments, and medications targeted to improve [cardiac output] are the primary targets to improve orthostatic intolerance.” They further state that this needs to be prospectively assessed in randomised, placebo-controlled trials.

Read more about PoTS

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