The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index; none of the 30 sources its claims cite is checked for support yet.
Cardiovascular autonomic dysfunction in Ehlers–Danlos syndrome—Hypermobile type
Open accessAbstract
Autonomic dysfunction contributes to health‐related impairment of quality of life in the hypermobile type of Ehlers–Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS‐related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt‐table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non‐pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short‐term physiological studies. Pharmacologic therapy is indicated for patients with moderate‐severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho‐social well‐being may generate a need for a more general evaluation and on‐going management and support. © 2017 Wiley Periodicals, Inc.
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37 No basis given · 21 Not checked yet · 7 Own interpretation · 1 Sources not found
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In the paper
“The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Abstract
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.
- Based: passes — The paper gives a reason why it holds.
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
“Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“and an intriguing association reported between multi-systemic pathologies including autonomic disturbances and germline duplications and triplications of the TSPAB1 gene encoding alpha 1 tryptase [Lyons et al., 2016].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > EVIDENCE FOR UNDERLYING MECHANISMS IN hEDS
What the sources say
- Not checked yetcites Lyons et al., 2016
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Symptoms can be highly debilitating in hEDS [Rowe et al., 1999;Hakim and Grahame, 2004;Mathias et al., 2011;De Wandele et al., 2014b].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
What the sources say
- Not checked yetcites Rowe et al., 1999
- Not checked yetcites Hakim and Grahame, 2004
- Not checked yetcites Mathias et al., 2011
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.
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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
“The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Abstract
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: unclear — It is unclear why the paper says it holds.
In the paper
“MVP is not common (approx.6%) in patients with hEDS [Dolan et al., 1997;McDonnell et al., 2006;Atzinger et al., 2011], and in most cases this is unlikely to be of clinical significance.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CONTROVERSIES Screening for Mitral Valve Prolapse
What the sources say
- Not checked yetcites Dolan et al., 1997;McDonnell et al., 2006;Atzinger et al., 2011
plain- 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
“In some cases this may also be a contributing factor”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > EVIDENCE FOR UNDERLYING MECHANISMS IN hEDS
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.
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
“MVP is not common (approx.6%) in patients with hEDS [Dolan et al., 1997;McDonnell et al., 2006;Atzinger et al., 2011], and in most cases this is unlikely to be of clinical significance.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CONTROVERSIES Screening for Mitral Valve Prolapse
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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In the paper
“Gazit et al. [2003] identified evidence of alpha-adrenergic and betaadrenergic hyper-responsiveness.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
What the sources say
- Not checked yetcites Gazit et al. [2003]
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — 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
“High circulating levels of histamine may be another mechanism contributing to cardiovascular dysfunction”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > EVIDENCE FOR UNDERLYING MECHANISMS IN hEDS
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. 28
- Probably not a substantial claim. 33
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
“Equally the causal relationships in hEDS are unclear though there are plausible mechanisms, and the evidence for the management in hEDS is lacking in that there are no published clinical trials.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
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.
- 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
“However, there are no clinical trials of treatment in hEDS, either in general or in specific subgroups based on pathophysiology.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Symptoms can be highly debilitating in hEDS.
plain- Asserted: passes — The authors put it forward as true.
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- 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.
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
“There has been no general hEDS population cohort study of cardiovascular autonomic dysfunction, and there has been one published case-control study of symptom reporting.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
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: unclear — It is unclear why the paper says 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
“Equally the causal relationships in hEDS are unclear though there are plausible mechanisms, and the evidence for the management in hEDS is lacking in that there are no published clinical trials.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
plain- 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: passes — The paper gives a reason why it holds.
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
“The causes of cardiovascular autonomic dysfunction in hEDS are unclear.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
plain- 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.
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
“In the general literature on the management of autonomic dysfunction there is evidence for the effectiveness of treatment strategies.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Symptoms can be highly debilitating in hEDS.
plaindirect- 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.
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
“Even where evidence exists, it is confounded by imprecision in definitions and diagnostic methods that further confound extrapolation from data to individual patients.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > MANAGEMENT AND CARE GUIDELINES
plaindirect- 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. 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
“There is no evidence that specific treatments should be targeted at subgroups of patients with hEDS.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
plain- 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.
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
“Level IV evidence of the associations with EDS arises from small cohort studies, case reports, and expert opinion.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > MANAGEMENT AND CARE GUIDELINES
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“As such guidance is principally based on expert consensus, but draws on Level I to III guidance published by international groups on the assessment and management of POTS and OI per se [Grubb et al., 2006;Lahrmann et al., 2006;Sheldon et al., 2015].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > MANAGEMENT AND CARE GUIDELINES
What the sources say
- Not checked yetcites Grubb et al., 2006;Lahrmann et al., 2006;Sheldon et al., 2015
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. 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 incidence, prevalence, and natural history of cardiovascular autonomic dysfunction in the hEDS population are unknown, as are the distribution and types of (co-associated) mechanisms that may trigger or influence these phenomena.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > WHAT WE NEED TO KNOW
plain- Asserted: passes — The authors put it forward as true.
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- 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. 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
“Using the standard nomenclature for guidelines Level I to III evidence for the management of cardiovascular autonomic dysfunction in hEDS is lacking; there are no published clinical trials.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > MANAGEMENT AND CARE GUIDELINES
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.
It may state two separate claims as one.
In the paper
“Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation.”
- Also stated in: § INTRODUCTION AND METHODS · plain
“While many symptoms of autonomic dysfunction have been observed clinically in hEDS, including cardiovascular, pupil, bladder, sweating dysfunction, and gastrointestinal dysmotility (see”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Abstract
What the sources say
- Not checked yetcites Aziz et al.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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.
- Also stated in: § INTRODUCTION AND METHODS · plain
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
“Mitral valve prolapse (MVP) can be associated with excessive catecholamines, orthostatic intolerance, and occasionally with dysrhythmias.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CONTROVERSIES Screening for Mitral Valve Prolapse
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Rowe et al. [1999] suggested that in some cases the association of OI with hEDS could be attributed to abnormal connective tissue in dependent blood vessels with veins distending excessively in response to ordinary hydrostatic pressures.This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
What the sources say
- Not checked yetcites Rowe et al. [1999]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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
“There is recognition of an association of POTS with fatigue [Schondorf et al., 1999], reduced quality of life [Benrud-Larson et al., 2002], and a greater incidence of migraine and syncope with POTS in patients with joint hypermobility syndrome compared to those without [Kanjwal et al., 2010].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
What the sources say
- Not checked yetcites Schondorf et al., 1999
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.
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
“When poorly controlled, these symptoms may also restrict treatment strategies for other symptomatic management including physical therapies.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
hedgedconditional- 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: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Histamine can induce hypotension and tachycardia [Frieri et al., 2013].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > EVIDENCE FOR UNDERLYING MECHANISMS IN hEDS
What the sources say
- Not checked yetcites Frieri et al., 2013
plaindirect- 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.
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
“There is growing recognition of an association between autonomic dys-function and Ehlers-Danlos syndrome -hypermobile type (hEDS).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > INTRODUCTION AND METHODS
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies by Mathias et al. [2011] and De Wandele et al. [2014a] suggest that neuropathy, connective tissue laxity, and vasoactive medication play a role in development of cardiovascular dysfunction in hEDS.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
What the sources say
- Not checked yetcites Mathias et al. [2011]
- Not checked yetcites De Wandele et al. [2014a]
hedgedconditional- 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 could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Also in the general literature, research has identified potentially pathogenic adrenergic [Fedorowski et al., 2016], muscarinic [Yu et al., 2012;Dubey et al., 2016], and other neural autoantibodies [Thieben et al., 2007;Li et al., 2014;Singer et al., 2016] in a significant percentage of cases with POTS and a subset of those with OH.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
What the sources say
- Not matchedcites Fedorowski et al., 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Yu et al., 2012;Dubey et al., 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Thieben et al., 2007;Li et al., 2014;Singer et al., 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- 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.
- Not matched
In the paper
“There is recognition of an association of POTS with fatigue [Schondorf et al., 1999], reduced quality of life [Benrud-Larson et al., 2002], and a greater incidence of migraine and syncope with POTS in patients with joint hypermobility syndrome compared to those without [Kanjwal et al., 2010].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
What the sources say
- Not checked yetcites Kanjwal et al., 2010
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: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“There is recognition of an association of POTS with fatigue [Schondorf et al., 1999], reduced quality of life [Benrud-Larson et al., 2002], and a greater incidence of migraine and syncope with POTS in patients with joint hypermobility syndrome compared to those without [Kanjwal et al., 2010].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > LITERATURE REVIEW
What the sources say
- Not checked yetcites Benrud-Larson et al., 2002
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In support of the hypothesis that this is one mechanism in hEDS, a study by Thieben et al. [2007] identified a hyperadrenergic state in 29% of cases of POTS from a general cohort though cases of hEDS were not specifically identified.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
What the sources say
- Not checked yetcites Thieben et al. [2007] source
plaincorrelational- 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.
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
“Also, normal cardiac anatomy does not rule out cardiovascular dysfunction.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CONTROVERSIES Screening for Mitral Valve Prolapse
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 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
“Suggested mechanisms include (listed based on clinical experience and in order of most common occurrence): Low blood pressure, increased peripheral venous dilation and blood pooling, low circulating blood volume, medications with side effects that trigger or impair autonomic responses, for example tricyclics, elevated circulating catecholamines, auto-immunity, particularly auto-antibodies directed”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CAUSAL ASSOCIATIONS WITH hEDS
hedgedconditional- 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: passes — The paper gives a reason why it holds.
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
“Many of the common symptoms relate to changes in posture.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > History
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.
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 prognosis remains uncertain with the outcomes ranging from virtually complete resolution of symptoms to long-term disability, which may be so severe as to affect education, employment, or socialization.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > SUMMARY
hedged- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Fu et al. [2011] and George et al. [2016] have shown that after a 3-month training programme, moderate gradual endurance and strength training can decrease upright heart rate, improve baroreflex sensitivity and heart rate variability, and improve quality of life.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CONTROVERSIES Screening for Mitral Valve Prolapse
What the sources say
- Not checked yetcites Fu et al., 2011
- Not checked yetcites George et al., 2016
plaindirect- 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.
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
“Physical deconditioning and poor aerobic fitness are common findings in patients chronically unwell with hEDS.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > CONTROVERSIES Screening for Mitral Valve Prolapse
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.
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
“Symptoms of OI can overlap with some features of cardiac dysrhythmias.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Physical examination
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.
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
“Fludrocortisone is a first line drug therapy for OI at doses of 100-200 mg daily (Level III evidence).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
plaindirect- 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.
- Rests on an assumption: Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
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
“Dihydroxyphenylserine titrated 100-200 mg three times daily reduces OH (Level I evidence).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
boosteddirect- 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.
- Rests on an assumption: Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
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 simple clinic room standing test can help assess whether a brief period of standing can provoke orthostatic symptoms in those with NMH, but provocation of hypotension usually requires more prolonged tilt table testing.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Physical examination
plainconditional- 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.
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
“Individuals with hEDS can develop cardiovascular autonomic dysfunction.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > SUMMARY
plainconditional- 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 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
“They occur when changing from a lying or sitting to a standing position, or with maintaining upright posture, and are improved but not always completely relieved by sitting or lying down.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > History
plaindirect- 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.
In the paper
“Pyridostigmine is a peripheral acetylcholinesterase inhibitor that increases synaptic acetylcholine in the autonomic ganglia and at peripheral muscarinic receptors [Raj et al., 2005].The drug can be effective for neurally mediated syncope and for POTS (Level I evidence).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
What the sources say
- Not checked yetcites Raj et al., 2005
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.
- Rests on an assumption: Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
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 diagnosis of NMH that is associated with recurrent syncope can be made clinically, and in most cases does not require formal tilt table testing.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Physical examination
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.
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 diagnosis is predominantly based upon taking a detailed personal and family history of symptoms, provoking circumstances, and accompanying complaints.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > 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: 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 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
“Simple clinic room tests can provide support for the diagnosis and other tests may be useful to exclude other diseases that can present in a similar manner.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > SUMMARY
hedgedcorrelational- 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.
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
“Specific conditions include POTS and NMH.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > SUMMARY
plain- 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.
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
“None of the treatments available is universally effective, and several treatments, used together, are likely to be needed.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
hedged- 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. 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, OH, and some forms of OI can be diagnosed in clinic without the need for complex tests.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Physical examination
plain- 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.
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
“Midodrine significantly reduces POTS symptoms and reduces the frequency of neurally mediated syncope (Level I evidence).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
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.
- Rests on an assumption: Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
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
“Ivabradine slows sinus heart rate without affecting blood pressure, and has been reported to be helpful in those with POTS (Level III evidence).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
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
“Its manifestations include symptoms related to inadequate cerebral perfusion and symptoms of heightened adrenergic tone.”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > SUMMARY
plaincorrelational- 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.
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
“Beta blockers can help with management of recurrent syncope, NMH, POTS, and OI (Level I evidence).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Treatment
plainconditional- 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.
- Rests on an assumption: Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
The paper relies on this without support.
Treatments shown to be effective for POTS and OI in the general population are also effective for cardiovascular autonomic dysfunction in hEDS.
“Such treatments have been applied to individual cases of hEDS, based on physiological findings.However, there are no clinical trials of treatment in hEDS, either in general or in specific subgroups based on pathophysiology.”
“As such guidance is principally based on expert consensus, but draws on Level I to III guidance published by international groups on the assessment and management of POTS and OI per se [Grubb et al., 2006;Lahrmann et al., 2006;Sheldon et al., 2015].”
The paper relies on this without support.
The consensus definitions of POTS, OH, NMH, and OI developed for general populations are valid for diagnosing these conditions in hEDS.
“The following consensus definitions 1 [Freeman et al., 2011;Sheldon et al., 2015] are applied:”
“This document uses definitions already proposed by international consensus and published in the general literature.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clinical features of HSD and hEDS are not limited to musculoskeletal and cutaneous symptoms (9). Associations exist with cardiovascular autonomic dysfunction (12), gastrointestinal difficulties (13), fatigue (12) and pain syndromes (14), gynecological and obstetric problems (15, 16), and mental health concerns (17–19).”
From Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain (2022) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Symptoms of orthostatic intolerance can be debilitating (12).”
From Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain (2022) · cites this paper as [12]
In the citing paper
“Cardiovascular autonomic dysfunction can include orthostatic hypotension, orthostatic intolerance, neurally‐mediated hypotension and postural orthostatic tachycardia syndrome (PoTS), the latter of which is commonly associated with HSD/hEDS. 66”
From Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know (2022) · cites this paper as [66]
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > EVIDENCE FOR UNDERLYING MECHANISMS IN hEDS
“germline duplications and triplications of the TSPAB1 gene encoding alpha 1 tryptase [Lyons et al., 2016].”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > References
“Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Physical examination
“(iii) the absence of orthostatic hypotension (>20 mm Hg drop in systolic blood pressure).”
§ Cardiovascular Autonomic Dysfunction in Ehlers-Danlos Syndrome-Hypermobile Type > Physical examination
“OH: a sustained reduction of systolic blood pressure by at least 20 mm Hg systolic or diastolic blood pressure of at least 10 mm Hg within 3 min of standing or head-up tilt to at least 60° angle on a tilt table.”
Citations
Cites
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“The following consensus definitions1 [Freeman et al., 2011; Sheldon et al., 2015] are applied: POTS: is a clinical syndrome usually characterized by: (i) frequent symptoms that occur with standing, such as lightheadedness, palpitations, tremor, generalized weakness, blurred vision, exercise…”
MethodSheldon, 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
Postural orthostatic tachycardia syndrome: the Mayo clinic experience
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Dysautonomia in the joint hypermobility syndrome
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EFNS guidelines on the diagnosis and management of orthostatic hypotension
Lahrmann, H., Cortelli, P., Hilz, M., Mathias, C. J., Struhal, W., & Tassinari, M. (2006) · European Journal of Neurology · doi:10.1111/j.1468-1331.2006.01512.x · Cited by 334 · cited 2×
“As such guidance is principally based on expert consensus, but draws on Level I to III guidance published by international groups on the assessment and management of POTS and OI per se [Grubb et al., 2006; Lahrmann et al., 2006; Sheldon et al., 2015].”
BackgroundCardiac origins of the postural orthostatic tachycardia syndrome
Fu, Q., VanGundy, T. B., Galbreath, M. M., Shibata, S., Jain, M., Hastings, J. L., Bhella, P. S., & Levine, B. D. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.02.043 · Cited by 329
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Autoimmune Basis for Postural Tachycardia Syndrome
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Postural tachycardia syndrome—current experience and concepts
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“Symptoms can be highly debilitating in hEDS [Rowe et al., 1999; Hakim and Grahame, 2004; Mathias et al., 2011; De Wandele et al., 2014b].”
BackgroundOrthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome
Rowe, P. C., Barron, D. F., Calkins, H., Maumenee, I. H., Tong, P. Y., & Geraghty, M. T. (1999) · The Journal of Pediatrics · doi:10.1016/s0022-3476(99)70173-3 · Cited by 230
Self-citationQuality of Life in Patients With Postural Tachycardia Syndrome
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Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome
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Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome
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Antiadrenergic autoimmunity in postural tachycardia syndrome
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Metadata
- Authors
- Hakim, A., O'Callaghan, C., De Wandele, I., Stiles, L., Pocinki, A., & Rowe, P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Hakim, Alan
- Venue
- American Journal of Medical Genetics Part C: Seminars in Medical Genetics
- Publisher
- Wiley
- Published
- 2017-02-04
- Volume
- 175
- Issue
- 1
- Pages
- 168-174
- ISSN
- 1552-4868 (ISSN-L)
- 1552-4876
- OpenAlex
- W2586005000
- Cited by
- 163
- References
- 45
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 17 · 2023: 14 · 2022: 19 · 2021: 40 · 2020: 15 · 2019: 11 · 2018: 5 · 2017: 7
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Medical Genetics Part C Seminars in Medical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- cardiac autonomic dysfunction, orthostatic intolerance, orthostatic hypotension, postural orthostatic tachycardia syndrome, gastrointestinal motility disorders, bladder dysfunction, tilt table test, catecholamine levels, non-pharmacological treatment, pharmacotherapy, quality of life
- MeSH terms
- Cardiovascular Diseases, Ehlers-Danlos Syndrome, Humans, Disease Management
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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.
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