Hoad A, Spickett G, Elliott J, Newton J
Northern CFS/ME Clinical Network; and Falls and Syncope Service, Institute of Cellular Medicine, Newcastle University, Newcastle; and ME NorthEast, County Durham, UK
Funding by ME Research UK and the Local CFS/ME Clinical Network
It has been suggested that postural orthostatic tachycardia syndrome (POTS) be considered in the differential diagnosis of those with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Currently, measurement of haemodynamic response to standing is not recommended in the UK NICE CFS/ME guidelines.
To determine the prevalence of POTS in patients with CFS/ME.
Fifty-nine patients with CFS/ME (Fukuda criteria) and 52 age- and sex-matched controls underwent formal autonomic assessment in the cardiovascular laboratory with continuous heart rate and beat-to-beat blood pressure measurement (Task Force, CNSystems, Graz Austria). Haemodynamic responses to standing over 2 min were measured. POTS was defined as symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of >30 beats per minute or to a heart rate of >120 beats per minute on standing.
Maximum heart rate on standing was significantly higher in the CFS/ME group compared with controls (106 ± 20 vs. 98 ± 13; P = 0.02). Of the CFS/ME group, 27% (16/59) had POTS compared with 9% (5) in the control population (P = 0.006). This difference was predominantly related to the increased proportion of those in the CFS/ME group whose heart rate increased to >120 beats per minute on standing (P = 0.0002). Increasing fatigue was associated with increase in heart rate (P = 0.04; r² = 0.1).
POTS is a frequent finding in patients with CFS/ME. We suggest that clinical evaluation of patients with CFS/ME should include response to standing. Studies are needed to determine the optimum intervention strategy to manage POTS in those with CFS/ME.
Postural orthostatic tachycardia syndrome (POTS) is a condition which causes a very large increase in heart rate and fall in blood pressure when people change from lying down to standing up. The consequences of this can include weakness, muscle aches and pains, and substantial disability. POTS is due to dysfunction of the autonomic nervous system, which controls many of the involuntary activities of the body.
Since many ME/CFS patients have problems with standing, and suffer symptoms such as dizziness, altered vision, nausea and fatigue, it has been suggested that some may also have POTS. We measured the change in heart rate on standing in 59 patients with ME/CFS, and found that 27% of them had POTS, compared with just 9% of healthy controls.
POTS is relatively common in ME/CFS patients, and their clinical evaluation should include autonomic function tests such as the response to standing.
Comment by ME Research UK
Disorders of the autonomic nervous system can have severe consequences, one of which is orthostatic intolerance; i.e., the inability to remain standing for long without suffering ill effects. Since one of the key difficulties that ME/CFS patients face is standing, most especially standing still, without experiencing symptoms such as dizziness, altered vision, nausea, fatigue, etc., it has been speculated that a thorough assessment of autonomic function might be a way to identify a specific definable subset of patients, or might even be diagnostic if the underlying mechanisms could be understood.
For a number of years, Prof. Julia Newton of the School of Clinical Medical Sciences, University of Newcastle, has been investigating fatigue in people with the autoimmune liver disease primary biliary cirrhosis, and has uncovered abnormalities of the autonomic nervous system contributing to their fatigue, which is itself related to low blood pressure and abnormalities of sleep. In addition, the fatigue in these patients is associated with excess mortality, which could also be linked to autonomic abnormalities. Could, she wondered, these abnormalities also be found in ME/CFS patients who experience many similar symptoms?
In a previous ME Reseach UK-funded study (read the report here), Prof. Newton examined a large group of people with ME/CFS using a well-validated battery of autonomic function tests which, by assessing heart rate and blood pressure responses to a variety of manoeuvres, can test cardiovascular reflexes. The Cardiovascular Laboratory in which the tests were done is one of the largest autonomic testing labs in Europe with all the necessary equipment and expertise for comprehensive autonomic testing. In the scientific paper reporting this work (published in the Quarterly Journal of Medicine, August 2007), Prof. Newton reported a clear association between ME/CFS and the symptoms of autonomic dysfunction. In three-quarters of the patients, autonomic dysfunction was present, and it was found that a COMPASS score greater than 32.5 appeared to be a robust, reproducible and objective diagnostic tool for identifying that significant sub-population of ME/CFS patients in whom autonomic dysfunction is a prominent disease feature. Also, the strong relationship between COMPASS scores and heart rate variability (an objective measure of autonomic function) gave good confirmatory evidence that the COMPASS scores are indeed identifying autonomic dysfunction. The researchers stressed, however, that a minority of patients did not have elevated COMPASS scores, suggesting that they might have identified subgroups of ME/CFS with potentially different origins for their illness.
In the most recent report from Prof. Newton’s group, the researchers have described the results of their efforts to assess the prevalence of one simple-to-measure aspect of dysautonomia, namely, postural orthostatic tachycardia syndrome (POTS), defined as symptoms of orthostatic intolerance associated with an increase in heart rate on moving from lying to standing. Importantly, the major finding was that significant POTS could be measured in a high proportion (27%) of the patients recruited via the specialist ME/CFS service, but in only 9% of the controls. Moreover, the POTS observed in the ME/CFS group was associated mainly with an increased heart rate to more than 120 beats per minute on standing, while increasing fatigue was significantly associated with the increase in heart rate.
The central finding is an important one: POTS is a relatively frequent finding in patients attending the Newcastle specialist CFS/ME service, leading the authors to suggest that the clinical evaluation of patients presenting with this illness should include heart rate responses to standing, a clear and easily measurable clinical sign. It remains unclear, however, whether the observed POTS should be viewed as a separate clinical entity distinct from ME/CFS, or whether patients experiencing POTS represent a particular subset of ME/CFS patients with the most marked symptoms. But whatever the case, the authors remark that the diagnosis of POTS (a potentially treatable condition) could be being missed in those attending clinical services as currently set-up for people with ME/CFS. And they suggest that at the very minimum a haemodynamic assessment of the response to standing should be included in the clinical assessment of patients attending ME/CFS clinical services.
POTS is the most common form of orthostatic intolerance without orthostatic hypotension, and can produce substantial disability among otherwise healthy people. One large series of patients with POTS (Thieben et al., Mayo Clinic Proceedings, 2007) reported the symptom burden to be significant and to include weakness, muscle aches and pains, and its findings also suggested a neuropathic basis for at least half the cases of POTS, and an autoimmune component for a substantial percentage of cases. Other studies have shown POTS to be accompanied by a range of autonomic nervous system abnormalities including vagal withdrawal and enhanced sympathetic modulation, and can be associated with findings consistent with pooling in the lower limbs, similar to pathophysiological mechanisms occurring in a proportion of people diagnosed with ME/CFS (see Standing Up for ME for a fuller discussion). Given these associations, it is important that POTS be recognised and managed, whether in ME/CFS or other groups of patients, and Prof. Newton’s findings suggest that current treatment regimes (which can include a range of pharmacological and non-pharmacological strategies) for the management of orthostatic hypotension and POTS should be incorporated into ME/CFS management programmes.
Read more (pdf 500 KB) in the Spring 2009 issue of Breakthrough.