Postural tachycardia syndrome – Diagnosis, physiology, and prognosis
Open accessAbstract
Postural tachycardia syndrome (POTS) is a heterogeneous clinical syndrome that has gained increasing interest over the past few decades due to its increasing prevalence and clinical impact on health-related quality of life. POTS is clinically characterized by sustained excessive tachycardia upon standing that occurs in the absence of significant orthostatic hypotension and other medical conditions and or medications, and with chronic symptoms of orthostatic intolerance. POTS represents one of the most common presentations of syncope and presyncope secondary to autonomic dysfunction in emergency rooms and in cardiology, neurology, and primary care clinics. The most sensitive method to detect POTS is a detailed medical history, physical examination with orthostatic vital signs or brief tilt table test, and a resting 12-lead electrocardiogram. Additional diagnostic testing may be warranted in selected patients based on clinical signs. While the precise etiology remains unknown, the orthostatic tachycardia in POTS is thought to reflect convergence of multiple pathophysiological processes, as a final common pathway. Based on this, POTS is often described as a clinical syndrome consisting of multiple heterogeneous disorders, with several underlying pathophysiological processes proposed in the literature including partial sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, and immune-mediated. These clinical features often overlap, however, making it difficult to categorize individual patients. Importantly, POTS is not associated with mortality, with many patients improving to some degree over time after diagnosis and proper treatment. This review will outline the current understanding of diagnosis, pathophysiology, and prognosis in POTS.
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- Findingreasoning
Clinical features of POTS often overlap, making it difficult to categorize individual patients.
“These clinical features often overlap, however, making it difficult to categorize individual patients.”
Quote in the paperSubstantial claim - Premisecitation
Approximately 50% of POTS patients evaluated at tertiary care centers exhibit a neuropathic phenotype associated with partial sympathetic denervation, usually due to a distal small fiber neuropathy producing sympathetic denervation of the lower limbs.
“approximately 50% of POTS patients evaluated at tertiary care centers exhibit a neuropathic phenotype associated with partial sympathetic denervation, usually due to a distal small fiber neuropathy producing sympathetic denervation of the lower limbs”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Low blood volume or hypovolemia is a common finding in POTS, with many patients reported to have deficits in red cell and plasma volume.
“Low blood volume or hypovolemia is a common finding in POTS, with many patients reported to have deficits in red cell and plasma volume”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
A small randomized placebo-controlled study showed that the norepinephrine transporter inhibitor atomoxetine acutely worsens orthostatic tachycardia and symptoms in POTS.
“A small, randomized, placebo-controlled study showed that the NET inhibitor atomoxetine acutely worsens orthostatic tachycardia and symptoms in POTS”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Green et al., 2013 source
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- Premisecitation
Chronic illness in POTS predisposes to impaired health-related quality of life and functional disability that limit activities of daily living.
“The presence of chronic illness in POTS predisposes to impaired health-related quality of life as well as functional disability that limit activities of daily living”
Quote in the paperNot a substantial claim0 of 2 sources checked
- Premisecitation
POTS diagnosis requires excluding other causes of sinus tachycardia, including acute physiological stimuli, dietary influences, medications, and other medical conditions.
“excluding other causes of sinus tachycardia including acute physiological stimuli (e.g.panic attacks, pain, exercise), dietary influences (e.g.caffeine, alcohol), medications (e.g.sympathomimetics, anticholinergics, rebound effects of β-blocker withdrawal), and other medical conditions”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationnone given
The orthostatic tachycardia in POTS is thought to reflect convergence of multiple pathophysiological processes as a final common pathway.
“While the precise etiology remains unknown, the orthostatic tachycardia in POTS is thought to reflect convergence of multiple pathophysiological processes, as a final common pathway.”
- Also stated in: § 4. Pathophysiology of POTS · hedged
“While the precise etiology remains unknown, orthostatic tachycardia in POTS is thought to reflect the convergence of multiple pathophysiological processes, as a final common pathway”
Quote in the paperSubstantial claim - Also stated in: § 4. Pathophysiology of POTS · hedged
- Premisecitation
Approximately 50% of POTS patients are reported to exhibit a hyperadrenergic phenotype characterized by excessive orthostatic tachycardia, standing plasma norepinephrine ≥600 pg/mL, a systolic blood pressure increase ≥10 mm Hg, or symptoms of sympathetic activation on standing.
“Approximately 50% of POTS patients are reported to exhibit a hyperadrenergic phenotype characterized by similar excessive orthostatic tachycardia, standing plasma norepinephrine ≥600 pg/mL, an increase in systolic BP ≥10 mm Hg, or symptoms of sympathetic activation”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
In patients under 19 years of age, the POTS heart rate threshold is higher: an increment of at least 40 bpm or an absolute upright heart rate of at least 120 bpm, because of physiological orthostatic tachycardia in adolescents and children.
“In patients < 19 years of age, there is a higher HR threshold for POTS (increment ≥ 40 bpm or absolute upright HR ≥ 120 bpm) due to physiological orthostatic tachycardia in adolescents and children”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Singer et al., 2012 source
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- Premisecitation
A loss-of-function single point mutation in the norepinephrine transporter gene SLC6A2 was identified in one family with orthostatic tachycardia.
“A loss of function single point mutation in the NET gene SLC6A2 was identified in one family with orthostatic tachycardia”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationcitation
This impairment can contribute to physical deconditioning.
“Many POTS patients have impaired health-related quality of life and functional disability (Benrud-Larson et al., 2003;Benrud-Larson et al., 2002), which can contribute to physical deconditioning.”
Quote in the paperNot a substantial claim - Premisecitation
A study by Mustafa et al. found blunted pressor responses to angiotensin II infusion in POTS with intact renal plasma flow, aldosterone secretion, and renal sodium reabsorption.
“Blunted pressor responses to angiotensin II infusion were observed in POTS with intact renal plasma flow, aldosterone secretion, and renal sodium reabsorption.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mustafa et al., 2012 source
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- Premisecitation
In an initial study, approximately 15% of POTS patients had low serum titers of ganglionic acetylcholine receptor antibodies.
“An initial study reported a low titer of ganglionic acetylcholine receptor (AChR) antibodies in the serum of approximately 15% of POTS patients (Thieben et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Thieben et al., 2007 source
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- Premisecitation
Autoantibodies targeting α1- and β-adrenergic receptors, as well as cardiac lipid raft-associated proteins, have been found in POTS patients.
“Circulating antibodies to α1-and β-adrenergic receptors and cardiac lipid raft-associated proteins have also been discovered in POTS (Fedorowski et al., 2017;Wang et al., 2013;Li et al., 2014).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
Long-term outcome studies in POTS generally indicate some symptom and quality-of-life improvement over time following appropriate diagnosis and treatment.
“A handful of studies have examined long-term outcomes in POTS, and have generally shown some improvement in symptoms and quality of life over time after appropriate diagnosis and treatment.”
Quote in the paperSubstantial claim - Premisecitation
In POTS, the physiological reactions to orthostatic stress are similar to those seen in deconditioning from prolonged bed rest or space flight, including tachycardia, exercise intolerance, and lower left ventricular mass, stroke volume, and blood volume.
“The physiological responses to orthostatic stress in POTS often resemble the clinical phenotype of patients with deconditioning from prolonged bed rest or space flight (e.g.tachycardia, exercise intolerance, and reductions in left ventricular mass, stroke volume, blood volume) (Fu et al., 2010a;Levine et al., 1997;Tank et al., 2011).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Some POTS patients may present with flushing and orthostatic intolerance in the absence of mast cell activation disorder.
“Some POTS patients may present with flushing and orthostatic intolerance in the absence of mast cell activation disorder”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shibao et al., 2005 source
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- Premisecitation
About 60% of adolescent POTS patients in a Mayo Clinic study reported general health improvement at a mean of approximately 20 months after initial evaluation and treatment with midodrine and β-blockers.
“In one study from the Mayo Clinic, about 60% of adolescent POTS patients reported general improvement in health at an approximate mean of 20 months following initial evaluation and treatment with medications such as midodrine and β-blockers (Lai et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lai et al., 2009 source
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- Premisecitation
A subgroup of POTS patients has been reported to present with episodic flushing and comorbid mast cell activation disorder.
“a subgroup of POTS patients has been reported to present with episodic flushing and comorbid mast cell activation disorder”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shibao et al., 2005 source
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- Premisecitation
In contrast, β-adrenergic autoantibodies from POTS serum acted agonistically on arteriole contractility, potentially facilitating tachycardia.
“In contrast, β-adrenergic autoantibodies elicited an agonistic effect on arteriole contractility, which could facilitate tachycardia.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Li et al., 2014
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- Premisecitation
The reported prevalence of deconditioning in POTS varies widely, from 20% to 90% of patients, depending on recruitment site and exercise protocol.
“The true prevalence of deconditioning in POTS also remains unclear, with studies showing large variations ranging from 20 to 90% of patients depending on site of patient recruitment and exercise protocols (Parsaik et al., 2012;Burkhardt et al., 2011;Arnold et al., 2013).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
In a small ex vivo study, α1-adrenergic autoantibodies from POTS serum partially antagonized contractility in rat cremaster arterioles, potentially causing compensatory sympathoneural activation and tachycardia.
“In a small ex vivo study with serum from POTS patients, α1-adrenergic autoantibodies exerted a partial peripheral antagonist effect on contractility in rat cremaster arterioles, which could elicit compensatory sympathoneural activation and tachycardia.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Li et al., 2014
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- Premisecitation
Other studies found excessive reductions in middle cerebral artery blood velocity during head-up tilt in POTS, possibly due to sympathetic or hypocapnic cerebral vasoconstriction.
“Others have shown excessive reductions in middle cerebral artery blood velocity measured by transcranial Doppler in POTS during HUTT, perhaps related to sympathetic-or hypocapnic-mediated cerebral vasoconstriction (Ocon et al., 2009;Medow et al., 2014;Del Pozzi et al., 2014;Jordan et al., 1998).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
A large proportion of POTS patients experience reduced health-related quality of life and functional disability.
“Many POTS patients have impaired health-related quality of life and functional disability (Benrud-Larson et al., 2003;Benrud-Larson et al., 2002), which can contribute to physical deconditioning.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Some studies found preserved dynamic cerebral perfusion and autoregulation in POTS patients during orthostatic stress.
“Some studies have shown that dynamic cerebral perfusion and autoregulation are preserved in POTS patients during orthostatic stress (Schondorf et al., 2005;Endo et al., 2014).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
In a small series, adolescents with severe POTS showed substantial improvement after diagnosis and treatment, with a mean follow-up of 92 months.
“In another small series, adolescents with florid POTS reported substantial improvement after diagnosis and treatment with a mean follow-up time of 92 months (Sousa et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sousa et al., 2012 source
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- Premisecitation
POTS patients appear to have a renin-aldosterone paradox in response to both hypovolemia and orthostatic challenge.
“POTS patients appear to have a “renin-aldosterone paradox” in response to both hypovolemia and orthostatic challenge.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Raj et al., 2005 source
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- Interpretationcitation
Many POTS patients may experience some improvement over time after diagnosis and appropriate treatment.
“Overall, these data suggest that many POTS patients may see some improvement over time following diagnosis and appropriate treatment.”
Quote in the paperSubstantial claim
- May combine two claims. 28
- Classified as probably not a substantial claim. 6
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Findingown dataDuring head-up tilt testing, orthostatic tachycardia is exaggerated, with mean heart rate increase over 30 bpm in both healthy subjects and POTS patients, suggesting that HUTT is less sensitive for diagnosis than active standing.
“Orthostatic tachycardia is exaggerated with HUTT, with the mean HR value over 30 bpm in both groups, suggesting less sensitivity of this method for diagnosis compared with active standing.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataDuring head-up tilt testing, healthy subjects show only a modest heart rate increase with no significant blood pressure change, whereas POTS patients show an excessive heart rate rise with stable blood pressure.
“Panel A: In a healthy subject, heart rate increases only modestly with HUTT, with no significant change in blood pressure.Panel B: In postural tachycardia syndrome (POTS), there is an excessive rise in HR during HUTT, with stable blood pressure.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationSyncope is not a predominant feature of POTS; only about 20-30% of patients pass out, usually due to vasovagal syncope.
“Syncope is not a predominant feature of POTS (only ~20-30% actually pass out, and this is usually thought to be due to vasovagal syncope)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shen et al., 2017 source
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PremisecitationPOTS diagnosis requires absence of sustained orthostatic hypotension, defined as a blood pressure drop greater than 20/10 mm Hg.
“in the absence of sustained orthostatic hypotension (drop in BP > 20/10 mm Hg)”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
Premisenone givenPOTS is a chronic disorder; acute POTS-like features with a viral infection usually resolve in a few days and are not POTS.
“Third, POTS is a chronic disorder.Many people can experience “POTS-like” features acutely with a viral infection, and this usually resolves in a few days.This acute presentation is not POTS.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThe minimal requirements to detect POTS on initial evaluation are a detailed medical history, physical examination with orthostatic vital signs, and a resting 12-lead electrocardiogram.
“The minimal requirements to detect POTS on initial evaluation are a detailed medical history, physical examination with orthostatic vitals, and a resting 12-lead electrocardiogram (ECG)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sheldon et al., 2015 source
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PremisecitationAcute restoration of blood volume with intravenous saline or the vasopressin analog desmopressin attenuates standing heart rate and improves symptom burden in POTS.
“acute restoration of blood volume with either intravenous saline or the vasopressin analog desmopressin attenuates standing HR and improve symptom burden in these patients”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationPOTS diagnosis requires a sustained heart rate increase of at least 30 bpm within 10 minutes of upright posture in adults, often with an absolute upright heart rate of at least 120 bpm.
“a sustained increase in HR of at least 30 bpm within 10 min of assuming the upright posture (often with absolute upright HR ≥ 120 bpm)”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationA study by Raj et al. showed an approximate 13% deficit in plasma volume in POTS patients using a nuclear medicine test, while matched healthy subjects had no deficit.
“A study by Raj et al. showed an approximate 13% deficit in plasma volume in POTS patients using a nuclear medicine test ( 131 Ilabeled human serum albumen), while matched healthy subjects had no deficit.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Raj et al.
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PremisecitationHead-up tilt table testing is sensitive for diagnosing POTS using the ≥30 bpm threshold, but it produces greater tachycardia and has less diagnostic specificity than standing.
“while HUTT is sensitive to diagnose POTS using the ≥30 bpm diagnostic threshold, it produces greater tachycardia and has less diagnostic specificity compared with standing”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Plash et al., 2013 source
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PremisecitationThere is significant diurnal variability in POTS, with greater orthostatic tachycardia and a higher percentage of patients meeting heart rate criteria in the morning than in the afternoon or evening.
“there can be significant diurnal variability in POTS, with the degree of orthostatic tachycardia and percentage of patients meeting HR criteria being higher in the morning compared with the afternoon or evening”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Brewster et al., 2012 source
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InterpretationreasoningPOTS is a clinical syndrome, not merely a physiological finding; the diagnosis cannot be made without typical symptoms that worsen upright and improve with recumbence.
“Finally, and most importantly, POTS is a clinical syndrome and not just a physiological finding.The diagnosis cannot be made in the absence of typical symptoms that are worse in the upright posture and better with recumbence.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationPOTS diagnosis requires symptoms of orthostatic intolerance for at least 6 months that are relieved by recumbence.
“with symptoms of orthostatic intolerance for at least 6 months that are relieved by recumbence”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThe hyperadrenergic state in POTS is usually secondary to hypovolemia or partial sympathetic denervation; in about 10% of patients the underlying cause is excessive central sympathetic discharge.
“This hyperadrenergic state is usually secondary to hypovolemia or partial sympathetic denervation; however, in ~10% of patients the underlying cause is excessive central sympathetic discharge”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Raj, 2006
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PremisecitationThe heart rate increase in POTS must be sustained; a transient increase immediately on standing that improves after about 45 seconds is likely a variant of initial orthostatic hypotension and is not itself POTS.
“First, the HR increase must be sustained.Many people will have a transient increase in HR immediately on standing that gets better after the first 45 s.This likely relates to a variant of initial orthostatic hypotension”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wieling et al., 2007 source
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PremisecitationPOTS is a heterogeneous clinical syndrome defined by sustained excessive sinus tachycardia on standing, without significant orthostatic hypotension, and with chronic orthostatic intolerance symptoms.
“Postural tachycardia syndrome (POTS) is a heterogeneous clinical syndrome that has gained increasing interest over the past few decades due to its increasing prevalence and clinical impact on health-related quality of life.POTS is clinically characterized by sustained excessive tachycardia upon standing that occurs in the absence of significant orthostatic hypotension and other medical conditions”
- Also stated in: § 1. Introduction · plain
“This is a heterogeneous clinical syndrome that is characterized by sustained and excessive sinus tachycardia upon standing, in the absence of orthostatic hypotension and with chronic symptoms of orthostatic intolerance”
Quote in the paperSubstantial claim0 of 2 sources checked- Also stated in: § 1. Introduction · plain
May combine two claims.
PremisereasoningPOTS is often described as a clinical syndrome consisting of multiple heterogeneous disorders, with proposed underlying processes including partial sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, and immune-mediated mechanisms.
“Based on this, POTS is often described as a clinical syndrome consisting of multiple heterogeneous disorders, with several underlying pathophysiological processes proposed in the literature including partial sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, and immune-mediated.”
Quote in the paperSubstantial claimMay combine two claims.
Premisenone givenPOTS has a strong female predominance of about 4-5:1 and primarily affects women of childbearing age.
“POTS has a strong female predominance (4-5:1), and primarily affects women of childbearing age.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe estimated prevalence of POTS is between 0.1% and 1% of the United States population.
“it is estimated to affect between 0.1 and 1% of the United States population”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Interpretationown dataIn the authors' experience, adult POTS patients can clinically improve, but cure is very unusual.
“In our experience, while adult POTS patients can clinically improve,”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningAutoantibodies may contribute to the pathophysiology of POTS in some patients, though their clinical significance remains uncertain.
“These collective data suggest that autoantibodies could contribute to pathophysiology of POTS in some patients, but further research is needed to understand the clinical significance of this finding.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationA follow-up study detected low levels of AChR antibodies in 5% of POTS patients and found no difference in seropositive rate or antibody levels compared with matched healthy controls.
“A follow-up study showed low AChR antibody levels in 5% of POTS patients, with no differences in seropositive rate or antibody levels from matched healthy subjects (Vernino et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vernino et al., 2016
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PremisecitationIn a Mayo Clinic study with an average 5-year follow-up, about 19% of POTS patients reported recovery, but a significant proportion reported ongoing functional disability.
“In another Mayo Clinic study looking at an average of 5 years of follow-up from initial evaluation, about 19% of patients reported that they had”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bhatia et al., 2016 source
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PremisecitationCirculating angiotensin II levels are approximately 2-fold higher in POTS, perhaps due to reduced levels or activity of its degrading enzyme ACE2.
“Circulating angiotensin II levels are approximately 2-fold higher in POTS, perhaps due to reduced levels or activity of its degrading enzyme ACE2”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Raj et al., 2005 source
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PremisecitationIn a 17-patient study, about one-third were symptom-free at follow-up, half had improved significantly, 12% remained highly symptomatic, and 62% were still taking medication.
“In this 17 patient study, approximately one-third of patients were completely asymptomatic, half reported significant improvement, 12% remained highly symptomatic, and 62% remained on pharmacological therapy on follow-up consistent with favorable disease progression.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sousa et al., 2012 source
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PremisecitationIn a prospective one-year follow-up study, over one-third of adult POTS patients no longer met POTS criteria during head-up tilt testing, and orthostatic symptoms improved.
“This study showed orthostatic symptom improvement and that over one-third of patients no longer met criteria for POTS during HUTT at follow-up (Kimpinski et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kimpinski et al., 2012 source
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PremisecitationIn POTS patients, short-term structured exercise reduces orthostatic tachycardia and improves quality of life, systemic hemodynamics, blood volume, left ventricular mass, and exercise tolerance.
“Regardless, structured short-term exercise programs can reduce orthostatic tachycardia and improve quality of life, systemic hemodynamics, blood volume, left ventricular mass, and exercise tolerance in POTS patients (Shibata et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Shibata et al., 2012 source
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InterpretationreasoningPOTS subtypes described in the literature often have overlapping clinical features, lack clearly accepted definitions, and are not currently useful as individual patient labels.
“While several”
- Also stated in: § 6. Conclusions · plain
“In reality, these”
Quote in the paperNot a substantial claim- Also stated in: § 6. Conclusions · plain
May combine two claims.
PremisecitationPOTS is thought to be a chronic condition not associated with significant mortality.
“While there is limited data on natural history, POTS is thought to reflect a chronic condition that is not associated with significant mortality (Sheldon et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sheldon et al., 2015 source
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Interpretationnone givenPOTS involves frequent near-fainting episodes that can lead to major reductions in health-related quality of life and functional disability in otherwise healthy young people.
“This syndrome is associated with frequent presyncopal episodes that can produce substantial impairment in health-related quality of life and functional disability in otherwise healthy young individuals.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationnone givenPOTS appears to result from convergence of multiple pathophysiological processes, and its precise etiology remains unknown.
“POTS appears to reflect convergence of multiple pathophysiological processes, and thus the precise etiology remains unknown.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationOcon et al. observed lower cerebral blood flow and impaired autoregulation in POTS patients with normal carbon dioxide levels, which may argue against hyperventilation as the cause.
“Possibly arguing against hyperventilation as the underlying cause, Ocon et al. showed reduced cerebral blood flow and autoregulation in normocapnic POTS patients (Ocon et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ocon et al., 2009 source
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The paper relies on this without support.
POTS is not associated with mortality.
“Importantly, POTS is not associated with mortality”
The paper relies on this without support.
Many POTS patients improve to some degree over time after diagnosis and proper treatment.
“with many patients improving to some degree over time after diagnosis and proper treatment”
The paper relies on this without support.
Many POTS patients report that their symptoms began after an acute viral illness.
“Many POTS patients report onset following an acute viral illness, perhaps suggesting a contribution of autoimmune factors.”
The paper relies on this without support.
POTS patients have symptoms of orthostatic intolerance despite normal blood pressure.
“POTS patients exhibit symptoms of orthostatic intolerance in the presence of normal BP, perhaps suggesting deficits in cerebrovascular autoregulation.”
The paper relies on this without support.
There is limited data on the natural history of POTS.
“While there is limited data on natural history, POTS is thought to reflect a chronic condition that is not associated with significant mortality (Sheldon et al., 2015).”
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 [1]
The Introduction estimates that POTS affects 0.1–1% of the United States population, while noting that its true prevalence is unknown. It calls POTS one of the most common presentations of presyncope and syncope secondary to autonomic dysfunction—not one of the most common autonomic nervous system disorders overall. The citing sentence broadens that comparison and omits the geographic qualifier. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPOTS can lead to impaired quality of life and functional disability, which can be economically devastating.
“Patients may experience impaired quality of life and functional disability, which can be economically devastating.1–3”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [1]
The Introduction and section 4.8 state that POTS can impair health-related quality of life and cause functional disability. The copy does not address whether those effects can be economically devastating; a search for economic and financial consequences found no supporting passage. Page numbers were not available in the copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrevalence estimates for POTS range from 0.2% to 1% of the US population, suggesting approximately 1-3 million affected persons.
“Estimates, based largely on clinical experience, range from 0.2% and 1% of the US population, which would suggest approximately 1–3 million affected persons (Arnold et al., 2018; Low et al., 2009; Sheldon et al., 2015).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Arnold et al., 2018
A typical POTS patient is a female aged 12 to 50 years, with a female-to-male ratio greater than 4:1.
“A typical patient with POTS is a 12 to 50 years old female (F:M ratio > 4:1) (Arnold et al., 2018; Sheldon et al., 2015).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Arnold et al., 2018
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].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [5]
Noncardiovascular POTS symptoms are not directly related to the observed haemodynamic disorders.
“These symptoms are not directly related to the observed haemodynamic disorders [3,5,7,20,35].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [5]
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 [5]
The chronotropic response during active standing testing may be blunted by a patient using the muscle pump.
“The chronotropic response may be blunted by patient using muscle pump [4,5,74]”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Adolescent heart-rate criteria differ between text and table
MinorThe text permits an absolute upright heart rate of at least 120 bpm as an alternative to a 40 bpm increase. Table 1 says a 40 bpm increase is required.
“In patients < 19 years of age, there is a higher HR threshold for POTS (increment ≥ 40 bpm or absolute upright HR ≥ 120 bpm)”
“Heart rate increase of ≥40 bpm within 10 min is required in adolescents age 12-19 years.”
Orthostatic hypotension thresholds disagree at the boundary
MinorThe diagnostic criteria in the text use a blood-pressure drop greater than 20/10 mm Hg, while Table 1 uses greater than or equal to 20/10 mm Hg. They classify a drop exactly at that threshold differently.
“in the absence of sustained orthostatic hypotension (drop in BP > 20/10 mm Hg)”
“Absence of orthostatic hypotension defined as a sustained drop in blood pressure ≥ 20/10 mm Hg within 3 min of upright posture.”
Tilt testing is assigned opposite diagnostic limitations
MinorThe text says tilt testing is sensitive but less specific than standing. The figure caption instead says the same result indicates less sensitivity.
“while HUTT is sensitive to diagnose POTS using the ≥30 bpm diagnostic threshold, it produces greater tachycardia and has less diagnostic specificity compared with standing”
“Orthostatic tachycardia is exaggerated with HUTT, with the mean HR value over 30 bpm in both groups, suggesting less sensitivity of this method for diagnosis compared with active standing.”
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References 83 · Cited by 186
Research works printed but not linked: 5
- Doherty, 2018, Mast cell activation disorder in pots, Auton. Neurosci.
- Goodman, 2018, Evaluation of a pots patient, Auton. Neurosci.
- Kirbis, 2013, Comparison of active standing test, head-up tilt test and 24-h ambulatory heart rate and blood pressure monitoring in diagnosing postural tachycardia, Funct. Neurol., 28, 39
- Newton, 2018, Managing fatigue in pots, Auton. Neurosci.
- Vernino, 2018, Autoimmunity and autoantibodies in pots: current state, Auton. Neurosci.
- Authors
- Arnold, A. C., Ng, J., & Raj, S. R.
- Affiliations
- Pennsylvania State University (US)
- University of Calgary (CA)
- Corresponding author
- Raj, Satish R.
- Venue
- Autonomic Neuroscience
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 215
- Pages
- 3-11
- ISSN
- 1566-0702 (ISSN-L)
- PMC
- PMC6113123
- OpenAlex
- W2791951917
- Cited by
- 186
- References
- 83
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 25 · 2023: 26 · 2022: 30 · 2021: 22 · 2020: 21 · 2019: 16 · 2018: 9
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autonomic Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HL122507)
- Canadian Institutes of Health Research (MOP142426)
- Cardiac Arrhythmia Network of Canada (SRG-15-P01-001, SRG-17-P27-001)
- 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, orthostatic intolerance, autonomic dysfunction, orthostatic tachycardia, tilt table test, pathophysiology, sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, prognosis, syncope
- MeSH terms
- Humans, Postural Orthostatic Tachycardia Syndrome
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