Autonomic Dysfunction (POTS) Studies

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Extended List of Studies (by year)

2015-2018

Cardiovascular characteristics of chronic fatigue syndrome. [Full Text] [PDF]
Bozzini S, Albergati A, Capelli E, Lorusso L, Gazzaruso C, Pelissero G, Falcone C. Biomed Rep. 2018

Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. [Full Text] [PDF]
Cambras T, Castro-Marrero J, Zaragoza MC, Díez-Noguera A, Alegre J. PLoS One. 2018

Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. [FullText] [PDF]
Castro-Marrero J, Zaragozá MC, González-Garcia S, Aliste L, Sáez-Francàs N, Romero O, Ferré A, Fernández de Sevilla T, Alegre J. J Sleep Res. 2018

Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome. [Full Text] [PDF]
Lynn M, Maclachlan L, Finkelmeyer A, Clark J, Locke J, Todryk S, Ng WF, Newton JL, Watson S.
Mediators Inflamm. 2018

The etiologic relation between disequilibrium and orthostatic intolerance in patients with myalgic encephalomyelitis (chronic fatigue syndrome). [Full Text] [PDF]
Miwa K, Inoue Y. J Cardiol. 2018

Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls. [Full Text] [PDF]
Orjatsalo M, Alakuijala A, Partinen M. J Clin Sleep Med. 2018

Lower regulatory frequency for postural control in patients with fibromyalgia and chronic fatigue syndrome. [Full Text] [PDF]
Rasouli O, Vasseljen O, Fors EA, Lorås HW, Stensdotter AK. PLoS One. 2018

Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection. [Full Text] [PDF]
Richardson AM, Lewis DP, Kita B, Ludlow H, Groome NP, Hedger MP, de Kretser DM, Lidbury BA.
J Transl Med. 2018

[HIGHLIGHT] Passive standing tests for the office diagnosis of postural tachycardia syndrome: New methodological considerations. [PDF]
Roma M, Marden CL, Rowe PC. Fatigue. 2018
We conclude that a minor methodological modification of the 10 min in-clinic passive standing test—namely the inclusion of a 2-minute supine post-test HR measure to help ascertain the representative supine HR—has the potential to improve the rates of diagnosing POTS among those with chronic orthostatic symptoms, and thus would increase the proportion of individuals who would qualify for treatment. Given the substantially lower diagnostic yield of abbreviated standing tests, we recommend a full 10 min of standing for the diagnosis of POTS.

Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case-Control Study.
[Full Text] [PDF]
Ruiz-Núñez B, Tarasse R, Vogelaar EF, Janneke Dijck-Brouwer DA, Muskiet FAJ. Front Endocrinol (Lausanne). 2018

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia. [Full Text]
Serrador JM, Quigley KS, Zhao C, Findley T, Natelson BH. NeuroRehabilitation. 2018

Low Sensitivity of Abbreviated Tilt Table Testing for Diagnosing Postural Tachycardia Syndrome in Adults With ME/CFS. [FullText] [PDF]
van Campen CLMC, Rowe PC, Visser FC. Front Pediatr. 2018

Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome. [*PDF]
Barnden LR, et al. Neuroimage Clin. 2016.

Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study. [PDF]
Newton JL, Finkelmeyer A, Petrides G, Frith J, Hodgson T, Maclachlan L, MacGowan G, Blamire AM.
Open Heart. 2016

Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. [Full Text]
Miwa K. Heart Vessels. 2015
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.

2010-2014

Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome. [Full Text]
Medow MS, Sood S, Messer Z, Dzogbeta S, Terilli C, Stewart JM. J Appl Physiol (1985). 2014
Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions.

[HIGHLIGHT] Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review. [Full Text]
Van Cauwenbergh D, Nijs J, Kos D, Van Weijnen L, Struyf F, Meeus M. Eur J Clin Invest. 2014
Via a systematic literature review, the authors concluded that there are differences in autonomous response between patients with CFS and healthy controls. The heart rate dynamic response during the head-up tilt test differs between patients with CFS and healthy controls, supporting the increased prevalence of postural orthostatic tachycardia syndrome.

Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. [PDF]
Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, De Wandele I, Da Silva H, Calders P.
Semin Arthritis Rheum. 2013

[HIGHLIGHT] Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. [PDF]
Nijs J, Ickmans K. J Intern Med. 2013
Postural orthostatic tachycardia syndrome and its relationship to CFS is discussed.

Several studies have been conducted to examine the presence of hyperexcitability of the central nervous system (i.e. central sensitization) in CFS, and all studies point in the same direction. Indeed, studies showed generalized hyperalgesia in CFS for a variety of sensory stimuli and in various tissues, including the skin, muscle tissue and the lungs. Other important scientific observations suggestive of CFS being a central nervous system disorder includes decreased grey matter volume in the brain evidence for brainstem dysfunction (white matter changes, hypoperfusion and hypometabolism in a manner that is consistent with autonomic nervous system dysfunction and dysfunctional endogenous analgesia, deregulated serotonergic neurotransmission in the rostral anterior cingulate, and the deficient hypothalamus pituitary adrenal‐axis functioning.

Heart Rate Variability During Sleep and Subsequent Sleepiness in Patients with Chronic Fatigue Syndrome. [PDF]
Togo F, Natelson BH. Autonomic Neuroscience: Basic & Clinical. 2013

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. [PDF]
Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. PLoS One. 2012
In a cognitive task study, patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive heart rate variability; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge.

Impaired blood pressure variability in chronic fatigue syndrome–a potential biomarker.
Frith J, Zalewski P, Klawe JJ, Pairman J, Bitner A, Tafil-Klawe M, Newton JL. QJM. 2012
At rest, low frequency heart rate variability (sympathetic) was significantly increased in CFS compared to controls, while parasympathetic markers were significantly reduced. Total diastolic blood pressure spectral power was increased across all domains, with a shift towards sympathetic and away from parasympathetic SBPV. On standing, overall systolic response was significantly reduced with reductions in both sympathetic and parasympathetic components.

Large and small artery endothelial dysfunction in chronic fatigue syndrome. [PDF]
Newton DJ, Kennedy G, Chan KK, Lang CC, Belch JJ, Khan F. Int J Cardiol. 2012

Chronic Fatigue Syndrome and the Autonomic Nervous System. [PDF]
Okamoto LE, Raj SR, Biaggioni I. Primer on the Autonomic Nervous System (Third Edition). 2012

Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes.
[Full Text] [PDF]
Okamoto LE, Raj SR, Peltier A, Gamboa A, Shibao C, Diedrich A, Black BK, Robertson D, Biaggioni I.
Clin Sci (Lond). 2012
The authors compared CFS and POTS (postural tachycardia syndrome) patients, concluding that most POTS patients met the 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.

Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging.
[Full Text] [PDF]
Hollingsworth KG, Hodgson T, Macgowan GA, Blamire AM, Newton JL. J Intern Med. 2011
Patients with CFS have markedly reduced cardiac mass and blood pool volumes, particularly end-diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls. The CFS group appeared to have a delay in the release of torsion.

Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome. [PDF]
Miwa K, Fujita M. Clin Cardiol. 2011

Increasing orthostatic stress impairs neurocognitive functioning in Chronic Fatigue Syndrome with Postural Tachycardia Syndrome. [PDF]
Ocon AJ, Messer Z, Medow M, Stewart J. Clin Sci (Lond). 2011
Increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy, and information processing in CFS/postural orthostatic tachycardia syndrome, but this is not related to changes in cerebral blood flow velocity. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress. [PDF]
Wyller VB, Barbieri R, Saul JP. Eur J Appl Physiol. 2011
CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress.

[HIGHLIGHT] Impaired cardiovascular response to standing in Chronic Fatigue Syndrome. [PDF]
Hollingsworth KG, Jones DE, Taylor R, Blamire AM, Newton JL. Eur J Clin Invest. 2010
Heart problems in CFS cause orthostatic intolerance, meaning that symptoms get worse when standing up. Impaired skeletal muscle metabolism is recognized in chronic fatigue syndrome (CFS). This study examined the relationship between skeletal and cardiac muscle function and symptoms on standing in CFS using magnetic resonance spectroscopy (MRS) and impedance cardiography.

Elevated nocturnal blood pressure and heart rate in adolescent chronic fatigue syndrome. [PDF]
Hurum H, Sulheim D, Thaulow E, Wyller VB. Acta Paediatr. 2010

Autonomic hyper-vigilance in post-infective fatigue syndrome.
Kadota Y, Cooper G, Burton AR, Lemon J, Schall U, Lloyd A, Vollmer-Conna U. Biol Psychol. 2010
Post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges.

2005-2009

Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function. [Full Text]
Hurwitz BE, Coryell VT, Parker M, Martin P, Laperriere A, Klimas NG, Sfakianakis GN, Bilsker MS.
Clin Sci (Lond). 2009
This study indicates that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition.

[HIGHLIGHT] Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS.
Maes M, et al. Neuro Endocrinol Lett. 2009.
ME/CFS is a multisystemic metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular disorders...Recently, Jason et al (2006) reported that the mean age of patients with myalgic encephalomyelitis/chronic fatigue syndrome dying from heart failure, i.e. 58.7 years, is significantly lower than the age of those dying from heart failure in the general US population, i.e. 83.1 years. These findings implicate that ME/CFS is a risk factor to cardio-vascular disorder. This review demonstrates that disorders in various IO&NS pathways provide explanations for the earlier mortality due to cardiovascular disorders in ME/CFS.

Lower ambulatory blood pressure in chronic fatigue syndrome. [Full Text]
Newton JL, Sheth A, Shin J, Pairman J, Wilton K, Burt JA, Jones DE. Psychosom Med. 2009
CFS patients have lower blood pressure and abnormal blood pressure regulation.

Enhanced vagal withdrawal during mild orthostatic stress in adolescents with chronic fatigue. [PDF]
Wyller VB, Barbieri R, Thaulow E, Saul JP. Ann Noninvasive Electrocardiol. 2008
CFS patients have heart problems, emerging during mild orthostatic stress.  Possible underlying mechanisms include low blood volume and abnormalities of reflex mechanisms.

Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study. [Full Text] [PDF]
Boneva RS, Decker MJ, Maloney EM, Lin JM, Jones JF, Helgason HG, Heim CM, Rye DB, Reeves WC.
Auton Neurosci. 2007

Symptoms of autonomic dysfunction in chronic fatigue syndrome.
Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DE. QJM. 2007
Symptoms of autonomic dysfunction were associated with CFS and correlated with the severity of the fatigue.

2000-2004

Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome. [PDF]
Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O’Neill W. In Vivo. 2004
The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 out of 87 patients (11.5%). With stress exercise, 21 patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 of these CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 out of 191 patients (2%) (p=0.0018).

Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications. [PDF]
Naschitz JE, Yeshurun D, Rosner I. Med Hypotheses. 2004
The authors hypothesize that dysautonomia is pivotal in the pathophysiology CFS and that manipulating the autonomic nervous system may be an effective treatment.

Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome. [PDF]
Khan F, Spence V, Kennedy G, Belch JJ. Clin Physiol Funct Imaging. 2003
Prolongation of acetylcholine-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.

The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome.
Streeten DH, Thomas D, Bell DS. Am J Med Sci. 2000
Delayed orthostatic hypotension and/or tachycardia caused by excessive gravitational venous pooling, which is correctable with external lower-body compression, together with subnormal circulating erythrocyte volume, are very frequent, although not invariably demonstrable, findings in moderate to severe CFS.

Pre-2000

Vestibular function test anomalies in patients with chronic fatigue syndrome.
Ash-Bernal R, Wall C 3rd, Komaroff AL, Bell D, Oas JG, Payman RN, Fagioli LR. Acta Otolaryngol. 1995
Researchers performed vestibular function testing performed on 11 CFS patients and concluded that results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction.

Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort. [PDF]
Lerner AM, Lawrie C, Dworkin HS. Chest. 1993
A group of patients with CFS (age 50 or younger, no risk factors for coronary artery disease) all had abnormal Holter readings, while 22.4 percent patients without CFS had abnormal readings (p < 0.01). Mild left ventricular dysfunction was noted in 8 of 60 patients. All 60 showed repetitively flat to inverted T waves alternating with normal T waves. Stress multiple gated acquisitions (MUGAs) (labeled erythrocytes with stannous pyrophosphate) were abnormal in eight patients. Although resting ejection fractions (EFs) were normal, with increasing workloads, gross left ventricular dysfunction occurred.