Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance

Abstract:

Central nervous system dysfunction with myalgic encephalomyelitis (ME) has been suggested as the main cause of chronic fatigue syndrome. Fluctuation of the symptom severity and hierarchy is a characteristic feature in ME patients. The characteristics of the sympathetic activation may differ between the “good days” and “bad days” in them.

Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a “good day” and a “bad day”, defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the “bad days” than on the “good days”. During the standing test on a “bad day”, 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a “good day” all the 24 patients maintained it.

Postural orthostatic tachycardia (POT) (increase in heart rate ≥30 beats/min) or severe POT (heart rate ≥120 beats/min) was observed on the “bad days” in 10 patients (43 %) who did not suffer from the severe tachycardia on the “good days”, suggesting the exaggerated sympathetic nervous activation.

In contrast, POT did not occur or severe POT was attenuated on the “bad days” in 5 patients (21 %) who developed POT or severe POT on the “good days”, suggesting the impaired sympathetic activation. Echocardiography revealed significantly lower mean values of both the left ventricular end-diastolic diameter and stroke volume index on the “bad days” compared with the “good days”.

In conclusion, in ME patients with orthostatic intolerance, the exaggerated activation of the sympathetic nervous system while standing appears to switch to the impaired sympathetic activation after the system is loaded with the additional accentuated stimuli associated with the preload reduction.

 

Source: Miwa K. Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. Heart Vessels. 2016 Sep;31(9):1522-8. doi: 10.1007/s00380-015-0744-3. Epub 2015 Sep 15. https://www.ncbi.nlm.nih.gov/pubmed/26374335

 

High flow variant postural orthostatic tachycardia syndrome amplifies the cardiac output response to exercise in adolescents

Abstract:

Postural orthostatic tachycardia syndrome (POTS) is characterized by chronic fatigue and dizziness and affected individuals by definition have orthostatic intolerance and tachycardia. There is considerable overlap of symptoms in patients with POTS and chronic fatigue syndrome (CFS), prompting speculation that POTS is akin to a deconditioned state.

We previously showed that adolescents with postural orthostatic tachycardia syndrome (POTS) have excessive heart rate (HR) during, and slower HR recovery after, exercise – hallmarks of deconditioning. We also noted exaggerated cardiac output during exercise which led us to hypothesize that tachycardia could be a manifestation of a high output state rather than a consequence of deconditioning.

We audited records of adolescents presenting with long-standing history of any mix of fatigue, dizziness, nausea, who underwent both head-up tilt table test and maximal exercise testing with measurement of cardiac output at rest plus 2-3 levels of exercise, and determined the cardiac output () versus oxygen uptake () relationship. Subjects with chronic fatigue were diagnosed with POTS if their HR rose ≥40 beat·min(-1) with head-up tilt.

Among 107 POTS patients the distribution of slopes for the , relationship was skewed toward higher slopes but showed two peaks with a split at ~7.0 L·min(-1) per L·min(-1), designated as normal (5.08 ± 1.17, N = 66) and hyperkinetic (8.99 ± 1.31, N = 41) subgroups. In contrast, cardiac output rose appropriately with in 141 patients with chronic fatigue but without POTS, exhibiting a normal distribution and an average slope of 6.10 ± 2.09 L·min(-1) per L·min(-1). Mean arterial blood pressure and pulse pressure from rest to exercise rose similarly in both groups.

We conclude that 40% of POTS adolescents demonstrate a hyperkinetic circulation during exercise. We attribute this to failure of normal regional vasoconstriction during exercise, such that patients must increase flow through an inappropriately vasodilated systemic circulation to maintain perfusion pressure.

© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

 

Source: Pianosi PT, Goodloe AH, Soma D, Parker KO, Brands CK, Fischer PR. High flow variant postural orthostatic tachycardia syndrome amplifies the cardiac output response to exercise in adolescents. Physiol Rep. 2014 Aug 28;2(8). pii: e12122. doi: 10.14814/phy2.12122. Print 2014 Aug 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246579/ (Full article)

 

Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) are frequently diagnosed with comorbid postural orthostatic tachycardia syndrome (POTS), suggesting a shared pathogenesis. The aim of this study was to examine the relationship between demographic characteristics, autonomic functioning and fatigue levels amongst CFS patients with and without comorbid POTS.

DESIGN AND SETTING: All patients presenting to the CFS Discovery Clinic between 2009 and 2012 completed a 20-min standing task as part of their initial assessment. Heart rate and pulse pressure were recorded at baseline, at 2-min intervals poststanding, at the end of the task and following a recovery period. Average heart rate and pulse pressure variability were calculated from this data. Age, gender, length of illness and self-reported fatigue scores were also recorded. POTS patients were diagnosed by an orthostatic increase in heart rate >30 beats per min, concomitant symptoms of orthostatic intolerance and no orthostatic hypotension. Differences in autonomic functioning between POTS and CFS patients were compared using independent samples t-tests, whilst logistic and linear regressions were performed to examine the contribution of autonomic functioning to task completion and perceived fatigue, respectively.

RESULTS:Comorbidity of CFS and POTS (CFS-POTS) was observed in 11% (33/306) of patients. CFS-POTS patients were significantly younger (P < 0.001), had a shorter length of illness (P = 0.034), experienced greater task difficulty (P = 0.002) and were able to stand for significantly shorter periods compared to the CFS-only patients (P < 0.001). CFS-POTS patients experienced significantly lower baseline diastolic blood pressure (P = 0.002), significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes (P = 0.002) and overall heart rate change (P < 0.001) were significant predictors of completion status, whereas heart rate variability (P < 0.001) and female gender (P < 0.001) were significant predictors of increased perceived task difficulty.

CONCLUSIONS:Haemodynamic and demographic differences between CFS-POTS and CFS-only patients suggest that the former group reflects a distinct subgroup of the CFS population. The findings highlight the utility of screening younger patients with fatigue for POTS, and identified heart rate variability as an important marker of fatigue for CFS patients in general.

© 2013 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Reynolds GK, Lewis DP, Richardson AM, Lidbury BA. Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort. J Intern Med. 2014 Apr;275(4):409-17. doi: 10.1111/joim.12161. Epub 2013 Nov 29. http://onlinelibrary.wiley.com/doi/10.1111/joim.12161/full (Full article)

 

Cognitive impairments associated with CFS and POTS

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994). Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS), is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009). Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment.

A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow) have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.

 

Source: Shanks L, Jason LA, Evans M, Brown A. Cognitive impairments associated with CFS and POTS. Front Physiol. 2013 May 16;4:113. doi: 10.3389/fphys.2013.00113. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655280/ (Full article)

 

Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning

In this issue of the Journal of Internal Medicine, Lewis and colleagues [1] provide compelling data for a novel subgroup within the chronic fatigue syndrome (CFS) population. They show that approximately 13% (24/179) of CFS patients have postural orthostatic tachycardia syndrome (POTS), a form of dysautonomia implying that when patients change their body position from supine to upright, their heart rate will increase abnormally (tachycardia). POTS is associated with several symptoms often seen in CFS patients: fatigue, lightheadedness, dizziness, neurocognitive deficits and exercise intolerance. Importantly, this was a confirmatory study of a previously published pilot study that found a prevalence rate for POTS of 29% in a smaller sample (n = 63) of CFS patients [2]. Another significant finding is the differences in fatigue severity, depressive thoughts and daytime hypersomnolence between CFS patients with and without POTS, providing evidence for the clinical importance of POTS in CFS.

You can read the full comment here: http://onlinelibrary.wiley.com/doi/10.1111/joim.12034/full

Comment on: Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. [J Intern Med. 2013]

 

Source: Nijs J, Ickmans K. Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. J Intern Med. 2013 May;273(5):498-500. doi: 10.1111/joim.12034. Epub 2013 Feb 8. http://onlinelibrary.wiley.com/doi/10.1111/joim.12034/full (Full article)

 

Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome

Abstract:

OBJECTIVES: A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.

METHODS: A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.

RESULTS: CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.

CONCLUSIONS: The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

© 2013 The Association for the Publication of the Journal of Internal Medicine.

Comment in: Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. [J Intern Med. 2013]

 

Source: Lewis I, Pairman J, Spickett G, Newton JL. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. J Intern Med. 2013 May;273(5):501-10. doi: 10.1111/joim.12022. Epub 2013 Jan 7. http://onlinelibrary.wiley.com/doi/10.1111/joim.12022/full (Full article)

 

Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome

Abstract:

Neurocognition is impaired in chronic fatigue syndrome (CFS). We propose that the impairment relates to postural cerebral hemodynamics.

Twenty-five CFS subjects and twenty control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75° with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFV). We used an n-back task with n ranging from 0 to 4 (increased n = increased task difficulty) to test working memory and information processing. We measured n-back outcomes by the number of correct answers and by reaction time. We measured CBFV, critical closing pressure (CCP), and CBFV altered by neuronal activity (activated CBFV) during each n value and every tilt angle using transcranial Doppler ultrasound.

N-back outcome in control subjects decreased with n valve but was independent of tilt angle. N-back outcome in CFS subjects decreased with n value but deteriorated as orthostasis progressed. Absolute mean CBFV was slightly less than in control subjects in CFS subject at each angle. Activated CBFV in control subjects was independent of tilt angle and increased with n value.

In contrast, activated CBFV averaged 0 in CFS subjects, decreased with angle, and was less than in control subjects. CCP was increased in CFS subjects, suggesting increased vasomotor tone and decreased metabolic control of CBFV. CCP did not change with orthostasis in CFS subjects but decreased monotonically in control subjects, consistent with vasodilation as compensation for the orthostatic reduction of cerebral perfusion pressure.

Increasing orthostatic stress impairs neurocognition in CFS subjects. CBFV activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS subjects; the increased CCP and vasomotor tone may indicate an uncoupling of the neurovascular unit during orthostasis.

 

Source: Stewart JM, Medow MS, Messer ZR, Baugham IL, Terilli C, Ocon AJ. Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1185-94. doi: 10.1152/ajpheart.00994.2011. Epub 2011 Dec 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311460/ (Full article)

 

Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome

Abstract:

CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as ‘mental fog’. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity).

A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups.

There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores.

Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

 

Source: Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci (Lond). 2012 Mar;122(5):227-38. doi: 10.1042/CS20110241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368269/ (Full article)

 

Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes

Abstract:

Several studies recognized an overlap between CFS (chronic fatigue syndrome) and POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal phenotype of POTS patients with CFS (CFS-POTS) to those without CFS (non-CFS-POTS), to determine whether CFS-POTS represents a unique clinical entity with a distinct pathophysiology.

We recruited 58 patients with POTS, of which 47 were eligible to participate. A total of 93% of them reported severe fatigue [CIS (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30) fulfilled criteria for CFS (CFS-POTS). The prevalence of CFS symptoms (Centers for Disease Control and Prevention criteria) was greater in the CFS-POTS group, but the pattern of symptoms was similar in both groups.

Physical functioning was low in both groups (RAND-36 Health Survey, 40±4 compared with 33±3; P=0.153), despite more severe fatigue in CFS-POTS patients (CIS fatigue subscale 51±1 compared with 43±3; P=0.016). CFS-POTS patients had greater orthostatic tachycardia than the non-CFS-POTS group (51±3 compared with 40±4 beats/min; P=0.030), greater low-frequency variability of BP (blood pressure; 6.3±0.7 compared with 4.8±1.0 mmHg2; P=0.019), greater BP recovery from early to late phase II of the Valsalva manoeuvre (18±3 compared with 11±2 mmHg; P=0.041) and a higher supine (1.5±0.2 compared with 1.0±0.3 ng/ml per·h; P=0.033) and upright (5.4±0.6 compared with 3.5±0.8 ng/ml per h; P=0.032) PRA (plasma renin activity).

In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.

 

Source: Okamoto LE, Raj SR, Peltier A, Gamboa A, Shibao C, Diedrich A, Black BK, Robertson D, Biaggioni I. Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes. Clin Sci (Lond). 2012 Feb;122(4):183-92. doi: 10.1042/CS20110200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203411/ (Full article)

 

Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome

Abstract:

BACKGROUND: 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.

OBJECTIVES: To determine prevalence of POTS in patients with CFS/ME.

DESIGN: Observational cohort study.

METHODS: 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.

RESULTS: 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; r(2) = 0.1).

CONCLUSION: 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.

 

Source: Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Dec;101(12):961-5. doi: 10.1093/qjmed/hcn123. Epub 2008 Sep 19. http://qjmed.oxfordjournals.org/content/101/12/961.long (Full article)