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Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1
Open accessAbstract
Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
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30 Not checked yet · 10 No basis given · 9 Own interpretation · 1 Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“and the cause of this condition remains unclear.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Background
What the sources say
- Supportedcites Raj and Robertson, 2018 source
The section “Need to Better Understand the Pathophysiologies Underlying POTS” says multiple disorders or mechanisms can lead to POTS and that how they contribute to patients’ symptoms is poorly understood. This supports the paraphrase that the cause of POTS remains unclear. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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- Supported
In the paper
“Postural orthostatic tachycardia syndrome (POTS) is common but the exact prevalence has not been determined”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Background
What the sources say
- Not checked yetcites Raj and Robertson, 2018 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Patients with POTS may simultaneously meet the diagnostic criteria for migraine, hypermobile Ehlers-Danlos syndrome (hEDS), mast cell activation syndrome (MCAS) or chronic fatigue syndrome (CFS) (Kavi et al., 2016; McDonald et al., 2014; Okamoto et al., 2012; Shaw et al., 2019).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Clinical associations & co-morbidities
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“An antecedent history of suspected viral infection is reported in 20–50% of patients (Sandroni et al., 1999; Shaw et al., 2019; Watari et al., 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Epidemiology & natural history
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In a large survey of over 4800 patients with a self- reported POTS diagnosis, the most common age at onset was 14 years (Shaw et al., 2019).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Epidemiology & natural history
What the sources say
- Not checked yetcites Shaw et al., 2019 source
plainn = 4,800- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The onset of POTS may be precipitated by a typical immunological stressor such as viral syndrome (often upper respiratory or gastrointestinal), physical trauma (such as concussion), menarche, pregnancy, or surgery (Boris and Bernadzikowski, 2018; Low et al., 1995; Mathias et al., 2011; Sandroni et al., 1999; Thieben et al., 2007; Watari et al., 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Epidemiology & natural history
What the sources say
- Not checked yetcites Boris and Bernadzikowski, 2018
- Not checked yetcites Low et al., 1995
- Not checked yetcites Mathias et al., 2011 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Despite these observations, a causal role of these autoantibodies in POTS is not established.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Antibodies and immunology of POTS
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“While circulating angiotensin II levels are high, POTS patients have impaired ability of the RAAS to expand blood volume (Li et al., 2015a; Mustafa et al., 2011; Raj et al., 2005; Stewart et al., 2006b).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pathophysiology of plasma volume and renin-angiotensin system
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A recent meta-analysis of ivabradine, a “funny channel” blocker that modulates cardiac sinus node activity, suggested benefit in lowering HR and providing symptomatic relief in POTS patients (Gee et al., 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pharmacologic management of POTS
What the sources say
- Not checked yetcites Gee et al., 2018
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Gastrointestinal symptoms are commonly reported by individuals with autonomic disorders, including POTS (Sullivan et al., 2005).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Gastrointestinal dysfunction in POTS
What the sources say
- Not checked yetcites Sullivan et al., 2005 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Absolute hypovolemia is commonly observed in POTS, with up to 70% of patients exhibiting deficits in plasma volume and red blood cell volume (Fu et al., 2010; Raj et al., 2005; Sheldon et al., 2015; Stewart et al., 2006a).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pathophysiology of plasma volume and renin-angiotensin system
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Several lines of evidence point to an autoimmune mechanism in at least some POTS patients as outlined above.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Role of immunotherapy
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations are not sufficient however.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Role of immunotherapy
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Conversely, orthostatic intolerance and tachycardia can be found in up to 40% of patients with hypermobility spectrum disorder or hypermobile Ehlers-Danlos Syndrome (Miller et al., 2020; Roma et al., 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Clinical associations & co-morbidities
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which is likely responsible for limited data on effective treatments.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Summary
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Further, a number of case reports, and retrospective case series have provided anecdotal evidence suggesting efficacy of IVIG in the treatment of refractory POTS and other forms of suspected autoimmune dysautonomia (Goodman, 2014; Schofield and Chemali, 2019; Weinstock et al., 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Role of immunotherapy
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Clinical diagnostic studies to identify gastrointestinal dysfunction are limited; however, gastrointestinal dysmotility is frequently diagnosed in POTS (DiBaise et al., 2018; Zhang et al., 2019).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Gastrointestinal dysfunction in POTS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Tests that measure the integrity of the cardiovagal and peripheral vasomotor adrenergic responses will be normal in most, but not all, POTS patients (Goodman, 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Clinical evaluation of POTS
What the sources say
- Not checked yetcites Goodman, 2018 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At this point, the clinical, laboratory, or autonomic features that should prompt consideration of immunotherapy are unknown.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Role of immunotherapy
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Along with increased water and salt intake, a progressive exercise program with recumbent aerobic exercise and leg resistance training transitioning to upright exercise has been shown to improve quality of life and reduce orthostatic HR in many patients (Fu and Levine, 2018, 2015; George et al., 2016; Sheldon et al., 2015; Shibata et al., 2012).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Non-pharmacologic management of POTS
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“POTS patients (Vernino and Stiles, 2018) and their close relatives (Boris et al., 2020; Shaw et al., 2019) have a higher than expected prevalence of autoimmune disorders including celiac disease (Penny et al., 2016), Hashimoto’s thyroiditis (Blitshteyn, 2015), Sjögren’s syndrome (Goodman et al., 2017), and systemic lupus erythematosus (SLE) (Tang et al., 2004).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Antibodies and immunology of POTS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- It may state two separate claims as one. 22
- Probably not a substantial claim. 13
In the paper
“the epidemiology of the disorder and natural history are not known (Raj and Robertson, 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Background
What the sources say
- Not checked yetcites Raj and Robertson, 2018 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Epidemiology & natural history
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The presentation seems to have two patterns – acute onset after one of the above triggers or with slowly progressive symptoms over a longer period of time (Thieben et al., 2007).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Epidemiology & natural history
What the sources say
- Not checked yetcites Thieben et al., 2007 source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The onset of POTS may be precipitated by immunological stressors such as a viral infection.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Since POTS predominantly affects adolescent or young adult women who would typically be in the midst of education or early careers, the condition can be severely debilitating and economically devastating (Bagai et al., 2011; Bourne et al., 2021a).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Background
What the sources say
- Not checked yetcites Bagai et al., 2011 source
- Not checked yetcites Bourne et al., 2021a
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Abstract
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Epidemiology & natural history
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Abstract
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The syndrome is heterogeneous in the sense that the spectrum of clinical features varies among patients, multiple etiologies may produce similar clinical phenotype and there is overlap with other clinically-defined syndromes.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Background
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“A recent clinical trial found propranolol and bisoprolol to have equal efficacy, with no significant benefit of pyridostigmine added to the beta-blocker (Moon et al., 2018).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pharmacologic management of POTS
What the sources say
- Not checked yetcites Moon et al., 2018
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These pathophysiological mechanisms are neither fully inclusive, nor completely exclusive. Fig. 1 summarizes the heterogenous and overlapping potential pathophysiological mechanisms in POTS. Many patients have features indicative of more than one mechanism.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Potential pathophysiological mechanisms
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The sensitivity and specificity of the pediatric heart rate criteria are not established, and POTS remains undefined under age 12 years despite patients under 12 presenting with similar syndromic findings, particularly in the setting of a familial predisposition.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pediatric considerations
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Current estimates derived from small samples or uncontrolled survey data suggest that approximately 40% of POTS patients experience migraine, 20–30% meet the diagnostic criteria for hypermobile Ehlers-Danlos syndrome (Miller et al., 2020; Roma et al., 2018), and about 15% carry a diagnosis of a co-morbid autoimmune disease.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Clinical associations & co-morbidities
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Serum immunoglobulins isolated from POTS patients have been reported to act as partial agonists to both α- and β-adrenergic receptors in vitro (Fedorowski et al., 2017; Li et al., 2014), a finding independently confirmed by several other groups (Vernino and Stiles, 2018) and expanded to include a wider range of G-protein coupled receptors (GPCRs) as targets (Kharraziha et al., 2020).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Antibodies and immunology of POTS
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“is associated with significant functional disability, such as decreased ability to participate in education, limited ability to work and generate an income, and decreased quality of life.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Summary
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Focused research studies on the pathophysiology and treatment of POTS have the potential to improve the lives of patients with POTS.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Summary
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“Fludrocortisone is frequently used in the treatment of POTS patients for the purposes of volume expansion, though evidence supporting its use is quite limited (Fortunato et al., 2014).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pharmacologic management of POTS
What the sources say
- Not checked yetcites Fortunato et al., 2014 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cardiovascular deconditioning (objectively demonstrated by low cardiac stroke volume and reduced cardiac mass) may also contribute in a significant way to the pathophysiology of POTS and exacerbate the symptomatology (Fu et al., 2010).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Potential pathophysiological mechanisms
What the sources say
- Not checked yetcites Fu et al., 2010
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Many POTS patients have a blood volume that is lower than expected for their size and sex, suggesting that hypovolemia may underlie some of the hemodynamic findings of POTS (Fu et al., 2010; Mar and Raj, 2014; Raj et al., 2005).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Potential pathophysiological mechanisms
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As many as 14% of POTS patients have a family member with POTS, 31% have a family member with orthostatic intolerance, 20% have a family member with joint hypermobility, and 45% have a family member with autoimmune disease (Boris et al., 2020).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Genetics
What the sources say
- Not checked yetcites Boris et al., 2020 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Beyond the expected placebo effects, intravenous infusion might provide a temporary increase in plasma volume independent of immunomodulatory effects.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Role of immunotherapy
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Midodrine, an oral alpha-adrenoceptor agonist prodrug, is used to promote venoconstriction and vasoconstriction in POTS patients and has shown benefit in small studies (Lai et al., 2009; Zhang et al., 2012).”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Pharmacologic management of POTS
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“POTS primarily affects females starting around puberty and through their child-bearing age”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Summary
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The pathophysiology is incompletely understood”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Summary
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Although there is no evidence for a monogenetic cause of POTS, increased POTS prevalence in family members suggests the presence of genetic predisposition.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Genetics
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Clinical observations may show a post-viral onset (Low et al., 1995; Schondorf and Low, 1993) suggesting the possibility of an immunological cause.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Potential pathophysiological mechanisms
What the sources say
- Not checked yetcites Low et al., 1995
- Not checked yetcites Schondorf and Low, 1993 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At this time, there are no data that long-term prognosis or response to therapies differ based on specific pathophysiological features.”
§ Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 > Potential pathophysiological mechanisms
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper relies on this without support.
POTS is common.
“Postural orthostatic tachycardia syndrome (POTS) is common but the exact prevalence has not been determined”
The paper relies on this without support.
Misdiagnosis of POTS is common.
“Although there is a consensus clinical definition for POTS, misdiagosis is common.”
The paper relies on this without support.
Clinical evaluation and treatment approaches for POTS are not standardized.
“The clinical evaluation of patients with suspected POTS is not standardized, nor are treatment approaches.”
The paper relies on this without support.
There is a lack of familiarity with POTS in the medical community.
“There is a lack of familiarity with POTS in the medical community”
The paper relies on this without support.
A majority of POTS patients report chronic symptoms with recurrent exacerbations.
“Significant symptomatic recovery has been reported by a subset of patients, but a majority report chronic symptoms with recurrent exacerbations.”
The paper relies on this without support.
No FDA-approved medications exist for the treatment of POTS.
“there are currently no FDA-approved medications for the treatment of POTS”
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?
The cited source says what the claim attributes to it.
In the citing paper
“Postural orthostatic tachycardia syndrome is a heterogeneous syndrome, with multiple causes that can produce a similar clinical phenotype.”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [8]
In the citing paper
“POTS has been shown to have a prevalence of 0.2% in cohort studies31–33 and predominately affects females at a 5:1 ratio.31,34–36”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [33]
Citations
Cites
The enteric nervous system and neurogastroenterology
Furness, J. B. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.32 · Cited by 1,619 · cited 2×
“Further research is needed about how the autonomic, ENS and immune systems interact with each other and with the host microbiota, in order to develop better diagnostic tests and potential new treatments.”
BackgroundFreeman, R., Wieling, W., Axelrod, F. B., Benditt, D. G., Benarroch, E., Biaggioni, I., Cheshire, W. P., Chelimsky, T., Cortelli, P., Gibbons, C. H., et al. (2011) · Autonomic Neuroscience · doi:10.1016/j.autneu.2011.02.004 · Cited by 1,243
Self-citationSheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W.-K., Calkins, H., Brignole, M., Raj, S. R., Krahn, A. D., Morillo, C. A., Stewart, J. M., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.03.029 · Cited by 1,013
Self-citationOrthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency
Shannon, J. R., Flattem, N. L., Jordan, J., Jacob, G., Black, B. K., Biaggioni, I., Blakely, R. D., & Robertson, D. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002243420803 · Cited by 594
Self-citationPadilla‐Walker, L. M., & Nelson, L. J. (2012) · Journal of Adolescence · doi:10.1016/j.adolescence.2012.03.007 · Cited by 558
Idiopathic postural orthostatic tachycardia syndrome: An attenuated form of acute pandysautonomia?
Schondorf, R., & Low, P. A. (1993) · Neurology · doi:10.1212/wnl.43.1_part_1.132 · Cited by 548
Postural orthostatic tachycardia syndrome: the Mayo clinic experience
Thieben, M. J., Sandroni, P., Sletten, D. M., Benrud-Larson, L. M., Fealey, R. D., Vernino, S., Low, P. A., Lennon, V. A., & Shen, W.-K. (2007) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(11)61027-6 · Cited by 516
Self-citation2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya‐Mitjans, À., de Lange, F. J., Deharo, J., Elliot, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martiın, A., et al. (2018) · Kardiologia Polska · doi:10.5603/kp.2018.0161 · Cited by 475
Self-citationThe neuropathic postural tachycardia syndrome
Jacob, G., Costa, F., Shannon, J. R., Robertson, R. M., Wathen, M., Stein, M., Biaggioni, I., Ertl, A., Black, B., & Robertson, D. (2000) · New England Journal of Medicine · doi:10.1056/nejm200010053431404 · Cited by 398
Self-citationPostural tachycardia syndrome: a heterogeneous and multifactorial disorder
Benarroch, E. E. (2012) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2012.08.013 · Cited by 370 · cited 1×
“…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).”
Background
Research works printed but not linked: 1
- Orban, 2020, Immunogenetic risk markers in postural orthostatic tachycardia syndrome [abstract]. Clin. Auton, Res, 30, 492
Cited by
Sorted by citations
Long COVID: pathophysiological factors and abnormalities of coagulation
Turner, S., Khan, A., Putrino, D. F., Woodcock, A. A., Kell, D. B., & Pretorius, E. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.03.002 · Cited by 247
Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden
Fedorowski, A., Fanciulli, A., Raj, S. R., Sheldon, R. S., Shibao, C. A., & Sutton, R. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00962-3 · Cited by 143
“In particular, there is substantial overlap with myalgic encephalitis/chronic fatigue syndrome (ME/CFS), a condition that is frequently encountered in both long COVID 1,11 and postural orthostatic tachycardia syndrome (POTS) 12 .”
InfluentialSelf-citationDiagnosis and management of postural orthostatic tachycardia syndrome
Raj, S. R., Fedorowski, A., & Sheldon, R. S. (2022) · Canadian Medical Association Journal · doi:10.1503/cmaj.211373 · Cited by 95
Self-citationKwan, A. C., Ebinger, J. E., Wei, J., Le, C. N., Oft, J. R., Zabner, R., Teodorescu, D. L., Botting, P. G., Navarrette, J., Ouyang, D., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00177-8 · Cited by 80
Metadata
- Authors
- Vernino, S., Bourne, K. M., Stiles, L. E., Grubb, B. P., Fedorowski, A., Stewart, J. M., Arnold, A. C., Pace, L. A., Axelsson, J., Boris, J. R., Moak, J. P., Goodman, B. P., Chémali, K. R., Chung, T. H., Goldstein, D. S., Diedrich, A., Miglis, M. G., Cortez, M. M., Miller, A. J., Freeman, R., Biaggioni, I., Rowe, P. C., Sheldon, R. S., Shibao, C. A., Systrom, D. M., Cook, G. A., Doherty, T. A., Abdallah, H. I., Darbari, A., & Raj, S. R.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Calgary (CA)
- Stony Brook University (US)
- University of Toledo Medical Center (US)
- Lund University (SE)
- New York Medical College (US)
- Pennsylvania State University (US)
- University of Utah (US)
- Karolinska University Hospital (SE)
- George Washington University (US)
- Mayo Clinic (US)
- Eastern Virginia Medical School (US)
- Johns Hopkins University (US)
- National Institutes of Health (US)
- Stanford Medicine (US)
- Beth Israel Deaconess Medical Center (US)
- Vanderbilt University Medical Center (US)
- Brigham and Women's Hospital (US)
- Uniformed Services University of the Health Sciences (US)
- University of California San Diego (US)
- Children's National (US)
- Corresponding author
- Raj, Satish R.
- ORCID
- Vernino, Steven
- Bourne, Kate M.
- Stiles, Lauren E.
- Grubb, Blair P.
- Fedorowski, Artur
- Stewart, Julian M.
- Arnold, Amy C.
- Pace, Laura A.
- Axelsson, Jonas
- Boris, Jeffrey R.
- Moak, Jeffrey P.
- Chémali, Kamal R.
- Chung, Tae H.
- Goldstein, David S.
- Miglis, Mitchell G.
- Cortez, Melissa M.
- Miller, Amanda J.
- Freeman, Roy
- Biaggioni, Italo
- Rowe, Peter C.
- Sheldon, Robert S.
- Shibao, Cyndya A.
- Systrom, David M.
- Cook, Glen A.
- Doherty, Taylor A.
- Abdallah, Hasan I.
- Darbari, Anil
- Raj, Satish R.
- Venue
- Autonomic Neuroscience
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 235
- Pages
- 102828
- ISSN
- 1566-0702 (ISSN-L)
- PMC
- PMC8455420
- OpenAlex
- W3170339939
- Cited by
- 304
- References
- 124
- Citations by year
- 2026: 59 · 2025: 77 · 2024: 75 · 2023: 46 · 2022: 44 · 2021: 2
- FWCI
- 39.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Autonomic Neuroscience (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Keywords
- postural orthostatic tachycardia syndrome, orthostatic intolerance, pathophysiology, diagnosis, non-pharmacological treatment, pharmacotherapy, autonomic dysfunction, fatigue, exercise intolerance, gastrointestinal symptoms
- MeSH terms
- Adolescent, Female, Heart Rate, Humans, National Institutes of Health (U.S.), United States, Consensus, Orthostatic Intolerance, 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.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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.
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