Postural tachycardia syndrome: a heterogeneous and multifactorial disorder
Open accessAbstract
Postural tachycardia syndrome (POTS) is defined by a heart rate increment of 30 beats/min or more within 10 minutes of standing or head-up tilt in the absence of orthostatic hypotension; the standing heart rate is often 120 beats/min or higher. POTS manifests with symptoms of cerebral hypoperfusion and excessive sympathoexcitation. The pathophysiology of POTS is heterogeneous and includes impaired sympathetically mediated vasoconstriction, excessive sympathetic drive, volume dysregulation, and deconditioning. POTS is frequently included in the differential diagnosis of chronic unexplained symptoms, such as inappropriate sinus tachycardia, chronic fatigue, chronic dizziness, or unexplained spells in otherwise healthy young individuals. Many patients with POTS also report symptoms not attributable to orthostatic intolerance, including those of functional gastrointestinal or bladder disorders, chronic headache, fibromyalgia, and sleep disturbances. In many of these cases, cognitive and behavioral factors, somatic hypervigilance associated with anxiety, depression, and behavioral amplification contribute to symptom chronicity. The aims of evaluation in patients with POTS are to exclude cardiac causes of inappropriate tachycardia; elucidate, if possible, the most likely pathophysiologic basis of postural intolerance; assess for the presence of treatable autonomic neuropathies; exclude endocrine causes of a hyperadrenergic state; evaluate for cardiovascular deconditioning; and determine the contribution of emotional and behavioral factors to the patient's symptoms. Management of POTS includes avoidance of precipitating factors, volume expansion, physical countermaneuvers, exercise training, pharmacotherapy (fludrocortisone, midodrine, β-blockers, and/or pyridostigmine), and behavioral-cognitive therapy. A literature search of PubMed for articles published from January 1, 1990, to June 15, 2012, was performed using the following terms (or combination of terms): POTS; postural tachycardia syndrome, orthostatic; orthostatic; syncope; sympathetic; baroreceptors; vestibulosympathetic; hypovolemia; visceral pain; chronic fatigue; deconditioning; headache; Chiari malformation; Ehlers-Danlos; emotion; amygdala; insula; anterior cingulate; periaqueductal gray; fludrocortisone; midodrine; propranolol; β-adrenergic; and pyridostigmine. Studies were limited to those published in English. Other articles were identified from bibliographies of the retrieved articles.
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More common than genetic NET deficiency is NET blockade from pharmacological agents, such as NE reuptake inhibitors, tricyclic antidepressants, and other sympathomimetic drugs.
“More common than genetic NET deficiency is NET blockade from pharmacological agents, such as NE reuptake inhibitors (e.g., bupropion), tricyclic antidepressants (e.g., nortriptyline), and other sympathomimetic drugs (e.g., methylphenidate) (15).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [15]
The ARTICLE HIGHLIGHTS passage says that increased norepinephrine levels more commonly reflect pharmacological NET blockade than the genetic NET deficiency described in a case. It names tricyclic antidepressants, selective NET inhibitors, and amphetamine-like drugs including methylphenidate, but does not name bupropion or nortriptyline as the citing sentence does. (LLM, conf=0.85)
Experimental — accuracy not yet measuredBehavioral and cognitive therapy has been used to obtain long-term control of symptoms, particularly when anxiety, hypervigilance, or catastrophizing behaviors are present.
“Behavioral and cognitive therapy has been used to obtain long-term control of symptoms, particularly when anxiety, hypervigilance, or catastrophizing behaviors are present (15).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [15]
In “Why Are Some Patients With POTS So Difficult to Treat?” (page not supplied), the paper identifies somatic hypervigilance as a factor in persistent symptoms and says behavioral-cognitive approaches are more likely than pharmacotherapy to improve quality of life. It does not report that therapy has been used to achieve long-term symptom control or specifically identify catastrophizing behaviors. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMechanisms described in POTS include autonomic denervation, hypovolemia, hyperadrenergic stimulation, deconditioning, and hypervigilance.
“A number of mechanisms have been described in patients with POTS,18 including autonomic denervation, hypovolemia, hyperadrenergic stimulation, deconditioning, and hypervigilance”
The pathophysiological mechanisms underlying POTS are thought to be heterogeneous.
“The pathophysiological mechanisms underlying POTS are thought to be heterogeneous (15).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [15]
Midodrine can cause urinary retention.
“Improvement in symptoms and orthostatic tachycardia can be associated with scalp tingling and goosebumps [58], and midodrine can cause urinary retention [67].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [67]
POTS-related syncope differs from classic vasovagal syncope.
“POTS-related syncope differs from classic vasovagal syncope (VVS), as the underlying symptoms are present constantly with occasional syncope associated with a preceding tachycardia and associated adrenergic symptoms. In contrast, VVS typically features episodic syncope and asymptomatic periods between attacks.1,4,7”
From Antiadrenergic autoimmunity in postural tachycardia syndrome (2017) · cites this paper as [1]
These contrasting effects provide an appealing explanation for the cardiovascular effects associated with upright posture in those so afflicted.
“These contrasting effects provide an appealing explanation for the cardiovascular effects associated with upright posture in those so afflicted.1,8”
From Antiadrenergic autoimmunity in postural tachycardia syndrome (2017) · cites this paper as [1]
These are recognized symptoms of POTS.
“These are recognized symptoms of POTS 5, 32, 33, 34.”
From The face of postural tachycardia syndrome – insights from a large cross‐sectional online community‐based survey (2019) · cites this paper as [33]
There is general consensus that POTS pathophysiology and clinical presentation are complex.
“There is a general consensus that POTS pathophysiology is complex as also is syndrome's clinical presentation [2,5].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [2]
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“…persistent symptoms such as low energy, headache, cognitive impairment, muscle fatigue, chest pain, non-specific generalized weakness, along with numerous gastrointestinal symptoms (Benarroch, 2012; Brignole et al., 2018; Fedorowski, 2019; Freeman et al., 2011; Raj, 2013; Sheldon et al., 2015).”
BackgroundPostural Orthostatic Tachycardia Syndrome
Bryarly, M., Phillips, L. T., Fu, Q., Vernino, S., & Levine, B. D. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.059 · Cited by 245 · see citing works
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Postural tachycardia syndrome: beyond orthostatic intolerance
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Antiadrenergic autoimmunity in postural tachycardia syndrome
Fedorowski, A., Li, H., Yu, X., Koelsch, K. A., Harris, V. M., Liles, C., Murphy, T. A., Quadri, S. M. S., Scofield, R. H., Sutton, R., et al. (2017) · EP Europace · doi:10.1093/europace/euw154 · Cited by 151 · see citing works
“It often leads to debilitating symptoms and uncertain long-term prognosis.(1) A number of treatment options have been proposed in POTS but their efficacy in the more severe forms is limited and often questioned.”
BackgroundInfluentialWhat is brain fog? An evaluation of the symptom in postural tachycardia syndrome
Ross, A. J., Medow, M. S., Rowe, P. C., & Stewart, J. M. (2013) · Clinical Autonomic Research · doi:10.1007/s10286-013-0212-z · Cited by 141 · see citing works
Ehlers–Danlos syndrome: how to diagnose and when to perform genetic tests
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Ehlers–Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study
Wallman, D., Weinberg, J., & Hohler, A. D. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.03.002 · Cited by 100 · see citing works
Autoimmune postural orthostatic tachycardia syndrome
Watari, M., Nakane, S., Mukaino, A., Nakajima, M., Mori, Y., Maeda, Y., Masuda, T., Takamatsu, K., Kouzaki, Y., Higuchi, O., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.524 · Cited by 94 · see citing works
“Postural orthostatic tachycardia syndrome (POTS) is the most common form of orthostatic intolerance characterized by lightheadedness, presyncope and palpitations, and nonorthostatic symptoms, such as fatigue, abnormalities of sleep, myofascial pain, nausea, and migraine headache.(2) Gastrointestinal (GI) disturbances…”
BackgroundInfluentialEvaluation of postural tachycardia syndrome (POTS)
Goodman, B. P. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.04.004 · Cited by 77 · see citing works
Efficacy of Therapies for Postural Tachycardia Syndrome: A Systematic Review and Meta-analysis
Wells, R., Elliott, A. D., Mahajan, R., Page, A., Iodice, V., Sanders, P., & Lau, D. H. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2018.01.025 · Cited by 67 · see citing works
Moon, J., Kim, D.-Y., Byun, J.-I., Sunwoo, J.-S., Lim, J.-A., Kim, T.-J., Shin, J.-W., Lee, W.-J., Lee, H. S., Jun, J.-S., et al. (2016) · Health and Quality of Life Outcomes · doi:10.1186/s12955-016-0548-x · Cited by 66 · see citing works
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“Orthostatic Intolerance and Postural Orthostatic”
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Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review
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Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome
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The genesis and presentation of anxiety in disorders of autonomic overexcitation
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Joint hypermobility syndrome subclassification in paediatrics: a factor analytic approach
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Domany, K. A., Hantragool, S., Smith, D. F., Xu, Y., Hossain, M., & Simakajornboon, N. (2018) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7058 · Cited by 29 · see citing works
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Aziz, Q., Harris, L. A., Goodman, B. P., Simrén, M., & Shin, A. (2025) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2025.02.015 · Cited by 27 · see citing works
Spectrum of gastrointestinal manifestations in joint hypermobility syndromes
Botrus, G., Baker, O., Borrego, E., Ngamdu, K. S., Teleb, M., Gonzales Martinez, J. L., Maldonado, G., Hussein, A. M., & McCallum, R. (2018) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2018.03.001 · Cited by 26 · see citing works
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Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine
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“22,23 The heterogeneous nature of POTS represents a challenge not only in understanding the disease but also in developing an effective treatment.”
Synergistic but separable sensory changes in postural tachycardia syndrome and chronic migraine
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Gleno-humeral abduction measurement in patients with Ehlers-Danlos syndrome
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Loganathan, P., Herlihy, D., Gajendran, M., Gonzalez, Z., Chavez, L. O., Espino, K., & McCallum, R. W. (2024) · Journal of Investigative Medicine · doi:10.1177/10815589231210486 · Cited by 8 · see citing works
- Authors
- Benarroch, E. E.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Benarroch, Eduardo E.
- Venue
- Mayo Clinic Proceedings
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 87
- Issue
- 12
- Pages
- 1214-1225
- ISSN
- 0025-6196 (ISSN-L)
- PMC
- PMC3547546
- OpenAlex
- W2030172951
- Semantic Scholar
- 733b1c775511cae660b88f7ed1902f36fdb338c4
- Cited by
- 370
- References
- 98
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 29 · 2023: 28 · 2022: 32 · 2021: 35 · 2020: 36 · 2019: 26 · 2018: 37 · 2017: 29 · 2016: 26 · 2015: 23 · 2014: 23 · 2013: 5
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Mayo Clinic Proceedings (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic intolerance, autonomic dysfunction, sympathoexcitation, vasoconstriction, hypovolemia, cardiovascular deconditioning, chronic fatigue, chronic dizziness, fibromyalgia, sleep disorders, anxiety and depression, fludrocortisone, midodrine, propranolol, pyridostigmine, exercise training, cognitive behavioral therapy, differential diagnosis, pathophysiology
- MeSH terms
- Drinking, Ehlers-Danlos Syndrome, Fibromyalgia, Gastrointestinal Motility, Headache, Humans, Sleep Initiation and Maintenance Disorders, Norepinephrine, Oxygen Consumption, Patient Education as Topic, Sodium, Dietary, Stroke Volume, Sympathetic Nervous System, Water, Exercise, Fatigue Syndrome, Chronic, Hypovolemia, Stockings, Compression, Postural Orthostatic Tachycardia Syndrome, Visceral Pain
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