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Cited by 352Cardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic ControlLong-Term Effects of COVID-19

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management

Open access
Fedorowski, A.·2019·Journal of Internal Medicine
DOI 10.1111/joim.12852
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Abstract

Postural orthostatic tachycardia syndrome ( POTS ) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affects younger individuals 15–45 years old with a distinct female predominance (≈80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, ‘brain fog’, dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head‐up tilt test with a non‐invasive beat‐to‐beat haemodynamic monitoring. Although long‐term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1–3 years. After the diagnosis has been established, patient should be thoroughly educated about non‐pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.

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Claims the paper makes

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  • Premisecitation

    In a specialized syncope unit, nearly one-third of patients aged 18-40 with unexplained syncope and pronounced orthostatic intolerance may satisfy POTS diagnostic criteria.

    “In a specialized syncope unit, almost one-third of patients aged 18-40 years with a history of unexplained syncope and pronounced orthostatic intolerance may meet the diagnostic POTS criteria [22].”
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  • Premisecitation

    The major consensus documents agree on most parts of the POTS diagnostic criteria.

    “The criteria are consistent in major parts across various consensus documents, although many authors emphasize the fact that overlap between POTS and other disorders, in particular orthostatic hypotension, vasovagal syncope, panic disorders, psychogenic pseudosyncope, chronic fatigue syndrome, Ehlers-Danlos syndrome and cardiac arrhythmias may exist and should be considered in complex cases [3][4]”
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  • Premisecitation

    The POTS diagnostic criteria have been endorsed by major international neurologic, autonomic, and cardiologic societies with slight modifications.

    “These criteria were subsequently endorsed by major international neurologic, autonomic and cardiologic societies with slight modifications [1,3,4]”
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  • Interpretationreasoning

    The heterogeneous symptoms, young age at onset, and presumptive triggers in POTS patients have led to various hypotheses about the syndrome's origin.

    “The heterogenous symptomatology, young age at onset and the presence of presumptive triggers in patient's history have led to the development of various hypotheses regarding syndrome's origin.”
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  • Premisecitation

    A substantial proportion of POTS patients (20-50%) share diagnoses with chronic fatigue syndrome and Ehlers-Danlos syndrome.

    “Interestingly, a substantial proportion of POTS patients (20-50%) share diagnoses with chronic fatigue syndrome (CFS) and Ehlers-Danlos syndrome (EDS) [31,33].”
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    Premisecitation

    POTS is a cardiovascular autonomic disorder variant marked by an excessive standing heart rate rise, orthostatic intolerance symptoms, and occasional syncope.

    “Postural orthostatic tachycardia syndrome (POTS) is a common, although not so well-known variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing, symptoms of orthostatic intolerance and occasional syncope [1][2][3][4].”
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    Premisecitation

    POTS affects younger people and shows a marked female predominance of about 80%.

    “The syndrome affects younger individuals, with a distinct predominance of women (%80%) [3,5].”
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    Premisecitation

    A typical POTS patient is a young woman around 25 years old whose first symptoms appear near age 15, although onset can extend into the fifth decade and about one-fifth of patients are men.

    “A characteristic patient with POTS is a young woman about 25 years old, reporting first symptoms at age around 15 years, although the range of disease onset may extend until fifth decade of life and one-fifth are men [21,22].”
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    Premisecitation

    POTS may overlap with orthostatic hypotension, vasovagal syncope, panic disorders, psychogenic pseudosyncope, chronic fatigue syndrome, Ehlers-Danlos syndrome, and cardiac arrhythmias, and this overlap should be considered in complex cases.

    “overlap between POTS and other disorders, in particular orthostatic hypotension, vasovagal syncope, panic disorders, psychogenic pseudosyncope, chronic fatigue syndrome, Ehlers-Danlos syndrome and cardiac arrhythmias may exist and should be considered in complex cases [3][4][5]20].”
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    Premisecitation

    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].”
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    Approximately 30-50% of all POTS patients faint.

    “Moreover, approximately 30-50% of all POTS patients faint [33,[35][36][37].”
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    Premisecitation

    POTS patients with chronic fatigue syndrome are typically younger and have shorter disease duration.

    “These patients are typically younger and have shorter disease duration [59].”
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    Premisecitation

    Positive antinuclear antibody tests occur in one of four POTS patients, and 20% report a history of autoimmune disorders such as Hashimoto's thyroiditis, rheumatoid arthritis, or Sjögren syndrome.

    “For instance, positive tests for antinuclear antibodies can be found in one of four POTS patients, whereas 20% report history of autoimmune disorders such as Hashimoto's thyroiditis, rheumatoid arthritis or Sj€ ogren syndrome [40]”
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    Premisecitation

    This mast cell activation POTS subset is characterized by flushing, dyspnoea, headache, excessive diuresis, and gastrointestinal symptoms such as diarrhoea, nausea, and vomiting, with elevated urine methylhistamine.

    “This specific subset of POTS is characterized by episodes of flushing, dyspnoea, headache, excessive diuresis and gastrointestinal symptoms such as diarrhoea, nausea and vomiting, accompanied by elevated urine methylhistamine [57].”
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    Premisecitation

    Cardiovascular POTS symptoms relate to inadequate and exaggerated standing heart rate increase, global postural haemodynamic instability with hypertensive or hypotensive tendency, cerebral hypoperfusion, venous pooling, and vascular tone dysregulation in specific areas.

    “This group of symptoms is related to an inadequate and exaggerated heart rate increase on standing, global postural haemodynamic instability, either hypertensive or hypotensive tendency, cerebral hypoperfusion, venous pooling, and disorders of vascular tone regulation in specific areas such as head, coronary arteries, skin, extremities [20,32,34,35] (Table 2).”
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    Premisecitation

    The hyperadrenergic subtype is characterized by high circulating norepinephrine during orthostasis, a tendency to orthostatic hypertension, and frequent extremity tremor, anxiety, migraine, and angina-like chest pain.

    “In this form, which is characterized by high level of circulating norepinephrine during orthostasis, patients demonstrate tendency to orthostatic hypertension and often complain of extremity tremor, anxiety, migraine and angina-like chest pain [55].”
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    Premisenone given

    According to the autonomic dysregulation hypothesis, increased central sympathetic outflow would explain inadequate sinus tachycardia, while venous pooling and reduced preload leading to compensatory heart rate elevation would be due to peripheral sympathetic denervation.

    “According to this hypothesis, increased central sympathetic outflow would explain inadequate sinus tachycardia, whereas venous pooling and reduced preload leading to compensatory heart rate elevation would be due to peripheral sympathetic denervation (Fig. 1).”
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    Premisecitation

    In a series of 38 POTS patients with gastrointestinal dysmotility, antiphospholipid antibodies were found in 76% and novel Sjögren antibodies in 42%.

    “In a series of 38 patients with POTS and gastrointestinal dysmotility, antiphospholipid antibodies were found in 76%, whereas novel Sjogren antibodies in 42% of all subjects [41].”
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    A hyperadrenergic subtype of POTS has been proposed.

    “In opposite to the 'hypovolemic' subtype, another form of POTS, the 'hyperadrenergic' subtype was proposed [55].”
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    Premisecitation

    Other proposed POTS pathomechanisms include autonomic cardiovascular regulation disorders, both abnormally increased sympathetic activity and circulating catecholamine excess, and peripheral sympathetic denervation leading to central hypovolaemia.

    “Other proposed pathomechanisms include disorders of autonomic cardiovascular regulation, both abnormally increased sympathetic activity and circulating catecholamine excess [7,50] and peripheral sympathetic denervation leading to central hypovolaemia [51][52][53].”
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    Premisecitation

    A subset of POTS patients show relative hypovolaemia and impaired renin-angiotensin-aldosterone regulation.

    “Further, a subset of POTS patients demonstrate relative hypovolaemia and impaired renin-angiotensin-aldosterone regulation [54].”
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    Premisecitation

    The female predominance and temporal association of POTS with antecedent viral infection, vaccination, or trauma resemble typical features of autoimmune disease.

    “First, the predominance of women and temporal association with an antecedent viral infection, vaccination or trauma are similar to the typical features of autoimmune disease [39].”
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    A specific focus has been on cardiovascular G-protein-coupled membrane complexes, including adrenergic, muscarinic, and angiotensin II type-1 receptors.

    “A specific focus was given cardiovascular G-protein-coupled membrane complexes, such as adrenergic, muscarinic and angiotensin II type-1 receptors The symptoms of POTS, especially [43,45] (Fig. 1).”
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    Premisecitation

    Chronic orthostatic intolerance is the predominant and pathognomonic feature of POTS, usually worsened by high ambient temperature, insufficient fluid intake, dehydration, physical strain, morning hours, or fever.

    “Although the predominant and pathognomonic feature of POTS is chronic orthostatic intolerance, usually exacerbated by additional factors such as high ambient temperature, insufficient fluid intake, dehydration, physical strain, morning hours or fever, POTS patients typically present”
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    Premisecitation

    Early clinical observations indicated that POTS often began with an acute infection, typically viral, and that its onset resembled Guillain-Barré syndrome.

    “Early clinical observations pointed to the fact that illness often started with an acute infection, typically viral, and that the onset was similar to Guillain-Barr e syndrome [7,17].”
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    Premisecitation

    In joint hypermobility syndrome, a variant of Ehlers-Danlos syndrome, POTS onset may be insidious and symptoms may develop over years starting in the teenage years.

    “In patients with joint hypermobility syndrome, a variant of Ehlers-Danlos Syndrome, the onset of POTS may be insidious and the symptoms may develop over years beginning with teenage [27].”
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    Premisecitation

    In a UK study, POTS patients waited about four years from presentation to correct diagnosis, and suspicion of a psychiatric condition was common.

    “In an UK study, patients waited approximately 4 years from presentation to obtain the correct diagnosis and a suspicion about psychiatric condition was common [33].”
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    The prevalence of different POTS symptoms varies widely, with some being more frequent and others less common.

    “The prevalence of different symptoms varies a lot, with some being more frequent, and other being less common [32,38].”
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    Interpretationreasoning

    These autoantibodies cannot satisfactorily explain the characteristic plethora of POTS symptoms; rather, they suggest overall immune system dysfunction and susceptibility to autoimmune disorders.

    “However, the presence of these autoantibodies cannot satisfactorily explain the characteristic plethora of POTS symptoms, which rather suggests the overall immune system dysfunction and susceptibility to autoimmune disorders.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning

    POTS therapy relies on patient education, non-pharmacological measures against orthostatic intolerance, and drugs directed at controlling heart rate, increasing peripheral vasoconstriction, and increasing intravascular volume, with limited efficacy in severe manifestations.

    “The therapy of POTS relies on patients' education, non-pharmacological measures against orthostatic intolerance and drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume with limited efficacy in severe manifestations.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Exercise training may be very effective and has been shown to alleviate symptoms of POTS-related deconditioning.

    “Exercise training may be very effective and has been shown to alleviate the symptoms of POTS-related deconditioning [66,67].”
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    Premisecitation

    In Ehlers-Danlos syndrome, characteristic POTS symptoms can be found in up to 40% of patients, and onset is typically not precipitated by viral infection.

    “In EDS, characteristic POST symptoms can be found in up to 40% of patients and the onset is typically not precipitated by viral infection [60].”
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    Premisenone given

    The gold standard for POTS diagnosis is head-up tilt test with non-invasive beat-to-beat haemodynamic monitoring.

    “The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring (Fig. 2).”
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    Premisecitation

    Ivabradine is usually regarded as an alternative to beta-blockers in POTS.

    “It is usually seen as an alternative to beta-blockers.”
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    Interpretationnone given

    POTS predominantly affects young women of reproductive age.

    “The syndrome affects predominantly young women in reproductive age.”
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    Ephedrine and pseudoephedrine are direct and indirect alpha1-adrenoreceptor agonists.

    “Direct and indirect a1-adrenoreceptor agonist.”
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    Droxidopa is a peroral norepinephrine precursor.

    “Peroral norepinephrine precursor.”
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    In POTS, echocardiography can reveal structural cardiac changes.

    “Structural cardiac changes”
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    Premisecitation

    The only Class IIA recommendations are exercise training against chronic symptoms and acute saline infusion in decompensated POTS, both with positive effects on plasma volume.

    “the only Class IIA recommendations are exercise training against chronic symptoms and acute saline infusion in decompensated POTS [3] both with positive effects on plasma volume [72].”
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    Class IIB recommendations include increased fluid and salt intake, midodrine, beta-blockers, fludrocortisone, pyridostigmine, clonidine, and alpha-methyldopa.

    “Among Class IIB recommendations are increased fluid and salt intake, midodrine, beta-blockers, fludrocortisone, pyridostigmine, clonidine and alpha-methyldopa [3].”
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    The long-term prognosis of POTS is not well explored.

    “The long-term prognosis of POTS is not well explored.”
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    Premisecitation

    Pyridostigmine is an acetylcholinesterase inhibitor.

    “Acetylcholinesterase inhibitor.”
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    Evidence for desmopressin in POTS is sparse and its efficacy is uncertain.

    “Sparse evidence exists. Efficacy uncertain [102]”
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    Clonidine is a centrally acting alpha2-adrenoreceptor agonist with an overall sympatholytic effect.

    “Centrally acting a2-adrenoreceptor agonist with overall sympatholytic effect.”
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    Interpretationcitation

    The overall effects of pharmacological therapy for POTS are modest, and most symptomatic patients remain severely affected even when combinations of drugs are used.

    “However, the overall effects of pharmacological therapy are modest and the most symptomatic patients remain severely affected by the disease even if combination of different drugs is applied [3,71].”
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    Interpretationnone given

    The aetiology of POTS is unknown, and autoimmunity, hyperadrenergic state, chronic hypovolaemia, and autonomic neuropathy have been proposed as underlying pathomechanisms.

    “The aetiology of POTS is unknown and autoimmunity, hyperadrenergic state, chronic hypovolaemia as well as autonomic neuropathy have been proposed as underlying pathomechanisms.”
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    Premisecitation

    Verapamil is a calcium channel blocker with a negative chronotropic effect.

    “This calcium channel blocker with negative chronotropic effect”
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    Verapamil can be tested in the hyperadrenergic POTS type associated with higher blood pressure, migraine, and chest pain.

    “can be tested in 'hyperadrenergic' type associated with higher BP, migraine, and chest pain [31].”
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43 of 43

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • POTS is one of the most common disorders of the autonomic nervous system, with an estimated prevalence of 0.1%-1%.

    “Postural orthostatic tachycardia syndrome is one of the most common disorders of the autonomic nervous system, with an estimated prevalence of 0.1%–1%.1,12,13”

    From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [12]

    The Introduction describes POTS as a common cardiovascular autonomic disorder, but does not rank it among the most common autonomic nervous system disorders. It gives an imprecise prevalence estimate of 0.2%–1.0% for the US population, rather than 0.1%–1%. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • POTS is a multisystem disorder that can be associated with a variety of comorbidities.

    “POTS is clearly a multisystem disorder that can be associated with a variety of comorbidities 5, 22.”

    From The face of postural tachycardia syndrome – insights from a large cross‐sectional online community‐based survey (2019) · cites this paper as [5]

  • 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 [5]

  • Multi-organ damage in acute COVID-19 is usually associated with transient sinus tachycardia, which resolves as the patient recovers.

    “Multi-organ damage in acute coronavirus disease-19 (COVID-19) is usually associated with transient sinus tachycardia164, which resolves as the patient recovers; however, prolonged tachycardia that persists after COVID-19 can pose a diagnostic conundrum.”

    From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [164]

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Da Costa J, 1871, On irritable heart: a clinical study of a form of a functional cardiac disorder and its consequences, Am J Med Sci, 61, 17
  2. Bjure A, 1927, Abnormal static circulatory phenomena and their symptoms: arterial orthostatic anemia as neglected clinical picture, Upsala läkaref förh, 33, 1
  3. Streeten DH, 1988, Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling, J Lab Clin Med, 111, 326
  4. Kavi L, 2016, A profile of patients with postural tachycardia syndrome and their experience of healthcare in the UK, Br J Cardiol, 23, 1
  5. Brinth L, 2015, Suspected side effects to the quadrivalent human papilloma vaccine, Dan Med J, 62, A5064

Cited by

Sorted by citations

Authors
Fedorowski, A.
Affiliations
Lund University (SE)
Corresponding author
Fedorowski, A.
ORCID
Fedorowski, A.
Venue
Journal of Internal Medicine
Publisher
Wiley
Published
2018-11-23
Volume
285
Issue
4
Pages
352-366
ISSN
  • 0954-6820 (ISSN-L)
  • 1365-2796
DOI
10.1111/joim.12852
OpenAlex
W2899473886
Semantic Scholar
6b74fda670513b048a38bbdf418f3f3e81cb8554
Cited by
352
References
100
Citations by year
2026: 37 · 2025: 61 · 2024: 54 · 2023: 53 · 2022: 60 · 2021: 36 · 2020: 32 · 2019: 19
FWCI
4.84
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
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 › Neurology › Long-Term Effects of COVID-19
Keywords
postural orthostatic tachycardia syndrome, cardiac autonomic dysfunction, orthostatic intolerance, head-up tilt, sympathetic denervation, reflex tachycardia, catecholamine excess, exercise training, non-pharmacological treatment, pharmacotherapy, symptom management, prognosis
MeSH terms
Cardiovascular System, Humans, Postural Orthostatic Tachycardia Syndrome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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