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Cited by 245Cardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic ControlLong-Term Effects of COVID-19

Postural Orthostatic Tachycardia Syndrome

Open access
Bryarly, Meredith, Phillips, Lauren T., Fu, Qi, Vernino, Steven, Levine, Benjamin D.·2019·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2018.11.059
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Abstract

Postural orthostatic tachycardia syndrome (POTS), the most common form of orthostatic intolerance in young people, affects approximately 500,000 people in the United States alone, typically young women at the peak of their education and the beginning of their working lives. This is a heterogeneous disorder, the pathophysiology and mechanisms of which are not well understood. There are multiple contributing factors and numerous potential mimics. This review details the most current views on the potential causes, comorbid conditions, proposed subtypes, differential diagnoses, evaluations, and treatment of POTS from cardiological and neurological perspectives.

AI snapshot

Written from the paper’s full text.

TL;DR

POTS is a heterogeneous syndrome of orthostatic intolerance, most common in young people, defined by a standing heart rate increment of ≥30 bpm (≥40 bpm in ages 12–19) without orthostatic hypotension, accompanied by symptoms. This review synthesizes proposed mechanisms, subtypes, differential diagnosis, evaluation, and management, emphasizing cardiovascular deconditioning and exercise-based reconditioning as central.

Key findings

  • POTS has a reported prevalence of 0.2%, affecting an estimated 500,000 Americans based on a 1999 report; the typical demographic is young women (mean age 30.2 ± 10.3 years, 86% women) with an average supine-to-upright heart rate increment of 44.2 ± 13.2 beats/min.
  • Onset can be subacute (13.8%), insidious (5.9%), or acute (12.5%), and is frequently preceded by a viral illness (42%) or occurs post-operatively (9.5%).
  • Cardiovascular deconditioning appears universally present: reduced cardiac size/mass by 16%, reduced blood volume by 20%, reduced stroke volume, and reduced peak oxygen uptake versus matched sedentary controls; a 3-month progressive exercise program leads to improvement or remission in the majority and was superior to propranolol for restoring upright hemodynamics and quality of life.
  • Proposed subtypes include neuropathic, hyperadrenergic (30%–60% of patients; standing norepinephrine >600 pg/ml), volume dysregulation (approximately 30% with <100 mEq 24-h urinary sodium), mast cell activation disorder, and autoimmunity; in one study, >50% of POTS patients had loss of distal lower-extremity sweat function.

Methods

  • Narrative review (JACC Focus Seminar); no primary cohort, systematic search, or meta-analysis is described.
  • Synthesizes prior literature and consensus statements (2011 and 2015) on pathophysiology, proposed subtypes, differential diagnosis, evaluation, and treatment.
  • Main analysis is qualitative synthesis; no new statistical analysis is reported.

Limitations

  • Stated: pathophysiology and mechanisms are not well understood; the disorder is heterogeneous; proposed subtypes are not mutually exclusive or clearly independent; autoantibody associations have not been convincingly proven pathophysiologically or diagnostically; the role of mast cell activation is controversial; no medication is FDA approved for POTS, and clinical trials supporting efficacy are absent.
  • Evident: as a narrative review, it lacks systematic search/selection criteria and relies on cited studies of varying designs, including small and retrospective studies; some cited findings have not been reproduced (e.g., the significance of nondipping is unclear).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jacc.2018.11.059

Cites

119 of 119 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

64 of 148 cited sources checked · 31 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Direct testing of autonomic function in POTS patients is often normal or appropriate for the hemodynamic stress.

    “direct testing of autonomic function in this patient population is often normal/appropriate for the hemodynamic stress (4).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol source
  • Premisecitation

    The pathophysiological mechanisms underlying POTS are thought to be heterogeneous.

    “The pathophysiological mechanisms underlying POTS are thought to be heterogeneous (15).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [15] Benarroch, 2012, Postural tachycardia syndrome: a heterogeneous and multifactorial disorder, Mayo Clin Proc source
  • Premisecitation

    In patients under 20 years of age, the HR increment with upright posture should exceed 40 beats/min to be considered clinically significant.

    “in patients under 20 years of age, the HR increment with upright posture should exceed 40 beats/min in order to be considered clinically significant (1,3).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] Sheldon, 2015, 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source

      The POTS Definition (Section 1; page not provided) gives a heart-rate increase of ≥40 beats/min on standing for individuals aged 12–19. The claim broadens that age range to everyone under 20 and says the increase must exceed 40, whereas the source includes exactly 40. It also presents the threshold as a general measure of clinical significance rather than one criterion of POTS. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [3] Freeman, 2011, Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome, Auton Neurosci source
  • Premisecitation

    There is a tight relationship between stroke volume and HR in men, healthy women, and women with POTS.

    “Figure 2B shows the tight relationship between stroke volume and HR in men, healthy women, and women with POTS (4,12).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [4] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol source

      The Discussion (page not provided) links smaller stroke volume to higher heart rate in POTS patients and describes a similar mechanism in young women. It does not establish a tight stroke-volume–heart-rate relationship across all three groups. The Methods (page not provided) report only one healthy male control, so the claim about men is not supported by this study. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [12] Fu, 2009, Menstrual cycle effects on sympathetic neural responses to upright tilt, J Physiol source

      The ‘Responses during upright tilt’ section reports that heart rate increased while stroke volume decreased in healthy men and women. It does not establish a tight stroke-volume–heart-rate relationship, and the ‘Study limitations’ section says all subjects were healthy, so the claim about women with POTS is not supported by this paper. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    Postflight orthostatic intolerance on return to Earth has been noted following both short- and long-term flights, especially in women astronauts.

    “Since the inception of space missions, a postflight orthostatic intolerance on return to Earth has been noted following both short-and long-term flights, especially in women astronauts.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [16] Fritsch-Yelle, 1996, Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight, J Appl Physiol (1985) source
    • cites [17] Buckey, 1996, Orthostatic intolerance after spaceflight, J Appl Physiol (1985) source
    • cites [18] Levine, 2002, Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight, J Physiol source

      The Discussion states that orthostatic intolerance has been observed after both short- and long-duration missions since the inception of the manned space program. It does not say it occurs especially in women; the Methods (Subjects) report that this study included only six male crew members. No page number is available for these passages. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • May combine two claims. 56
  • Classified as probably not a substantial claim. 27

  • May combine two claims.

    Premisecitation

    Nondipping POTS patients demonstrate significantly greater orthostatic HR increment and a significantly greater orthostatic plasma NE rise compared with matched dipping controls.

    “These patients also demonstrate significantly greater orthostatic HR increment and a significantly greater orthostatic plasma NE rise compared with matched dipping controls (56),”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [56] Figueroa, 2014, Decreased orthostatic adrenergic reactivity in non-dipping postural tachycardia syndrome, Auton Neurosci source

      The Results (Autonomic Function Tests, BP monitoring, and Laboratory Data; page not provided) report the opposite direction: dipping POTS patients had significantly greater orthostatic heart-rate increments and plasma norepinephrine increases than non-dippers. The Discussion likewise describes lower adrenergic reactivity in non-dippers. (LLM, conf=0.95)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    POTS has a prevalence of 0.2%.

    “with a prevalence of 0.2% (1)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Sheldon, 2015, 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source

  • May combine two claims.

    Premisecitation

    Healthy women have smaller stroke volumes and higher HRs compared with healthy men, whereas women with POTS have both an exaggerated fall in stroke volume and an apparent compensatory rise in HR.

    “healthy women have smaller stroke volumes and higher HRs compared with healthy men, whereas women with POTS have both an exaggerated fall in stroke volume and an apparent compensatory rise in HR.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [4] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol source

      The Discussion (page unavailable) reports smaller upright stroke volume and greater heart rate in POTS patients than in healthy controls, and describes the tachycardia as an apparent compensatory response. It also says healthy women have smaller hearts than men, but does not establish that healthy women have smaller stroke volumes and higher heart rates than men. Nor does it directly establish an exaggerated fall in stroke volume in the POTS patients studied, as distinct from a smaller upright stroke volume. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [12] Fu, 2009, Menstrual cycle effects on sympathetic neural responses to upright tilt, J Physiol source

      The Responses during upright tilt section reports lower stroke volumes in healthy women than men, while heart rates only tended to be higher. The Study limitations section says all participants were healthy; the paper does not support the claim about an exaggerated stroke-volume fall or compensatory heart-rate rise in women with POTS. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Pre-syncope is much more common than syncope in POTS, but POTS coexists with episodes of neurally mediated (reflex) syncope.

    “Pre-syncope is much more common than syncope in POTS, but it is not infrequent that POTS coexists with episodes of neurally mediated (reflex) syncope (1).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Sheldon, 2015, 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source

  • May combine two claims.

    Premisecitation

    Some POTS patients have persistently low plasma volumes, which evidence suggests is perhaps secondary to impaired function of the renin-angiotensin-aldosterone system.

    “Some POTS patients have been noted to have persistently low plasma volumes (32,(42)(43)(44), which evidence suggests is perhaps secondary to impaired function of the renin-angiotensin-aldosterone system.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [32] Raj, 2007, Blood volume perturbations in the postural tachycardia syndrome, Am J Med Sci source
    • cites [42] Stewart, 2009, Defects in cutaneous angiotensin-converting enzyme 2 and angiotensin-(1-7) production in postural tachycardia syndrome, Hypertension source

      The Introduction (page unavailable) describes a low-flow POTS subgroup with hypovolemia. The Discussion (page unavailable) suggests an ACE2-related angiotensin defect, but links it to excessive vasoconstriction, not to the cause of low plasma volume. The paper also does not establish that the low volume is persistent. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [43] Li, 2015, [Relationship between 24-hour urinary sodium and renin-angiotensin-aldosterone system in children with postural tachycardia syndrome], Zhonghua Yi Xue Za Zhi

  • May combine two claims.

    Premisecitation

    Exercise training has been demonstrated to expand blood volume and increase cardiac size and mass in POTS patients and result in a prominent decrease in symptoms.

    “the positive response these patients have to exercise training, which has been demonstrated to expand blood volume and increase cardiac size and mass in POTS patients and result in a prominent decrease in symptoms (4,63,64).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [4] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol source
    • cites [63] Dorfman, 2007, Cardiac atrophy in women following bed rest, J Appl Physiol (1985) source
    • cites [64] George, 2016, The international POTS registry: Evaluating the efficacy of an exercise training intervention in a community setting, Heart Rhythm source

  • May combine two claims.

    Premisecitation

    In POTS patients, cardiac output and stroke volume were lower, and total peripheral vascular resistance higher, during the early-follicular phase.

    “However, in POTS patients, cardiac output and stroke volume were lower, and total peripheral vascular resistance higher, during the early-follicular phase.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [45] Fu, 2010, Menstrual cycle affects renal-adrenal and hemodynamic responses during prolonged standing in the postural orthostatic tachycardia syndrome, Hypertension source

      The Results (EFP versus MLP; page not provided) report lower cardiac output and stroke volume and greater total peripheral resistance in POTS women during the early-follicular phase than the mid-luteal phase. The claim omits the condition that these differences appeared only after 30 minutes of standing; supine measurements and responses during the initial 30 minutes did not differ between phases. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Multiple parameters associated with deconditioning have been demonstrated in POTS patients, including reduced cardiac size and mass (by 16%), reduced blood volume (by 20%), reduced stroke volume, and reduced peak oxygen uptake (VO2 peak) when compared with matched sedentary controls.

    “Multiple parameters associated with deconditioning have also been demonstrated in POTS patients, including reduced cardiac size and mass (by 16%), reduced blood volume (by 20%), reduced stroke volume, and reduced peak oxygen uptake (VO 2 peak) when compared with matched sedentary controls (4).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol source

      The Discussion (POTS and “deconditioning”; page unavailable) reports approximately 16% lower left ventricular mass, 20% lower blood and plasma volume, and markedly smaller upright stroke volume in POTS patients than in healthy sedentary controls. The Results (Exercise training effects; page unavailable) show that peak oxygen uptake increased after training in POTS patients, but do not establish that it was lower than in controls. The 16% figure applies specifically to left ventricular mass, not cardiac size as well. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In POTS patients who do get overnight polysomnography, no objective sleep parameter abnormalities are typically identified, and findings are comparable to those of healthy controls.

    “In POTS patients who do get overnight polysomnography, no objective sleep parameter abnormalities are typically identified, and findings are comparable to those of healthy controls (84,85).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [84] Bagai, 2016, Objective sleep assessments in patients with postural tachycardia syndrome using overnight polysomnograms, J Clin Sleep Med source
    • cites [85] Pengo, 2015, Characterisation of sleep disturbances in postural orthostatic tachycardia syndrome: a polysomnography-based study, Sleep Med source

  • May combine two claims.

    Premisecitation

    Both POTS and CFS patients share many of the same characteristics including small hearts and lab markers of excessive sympathetic activation.

    “Not surprisingly, both POTS and CFS patients share many of the same characteristics including small hearts (81) and lab markers of excessive sympathetic activation;”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [81] Miwa, 2008, Small heart syndrome in patients with chronic fatigue syndrome, Clin Cardiol source

      The Abstract reports small hearts in 61% of patients with CFS, compared with 24% of controls. That supports the CFS portion of the cited small-heart claim, but the study did not examine POTS patients, so it cannot establish that both groups share this characteristic. The citation is attached to “small hearts,” not to the subsequent claim about lab markers. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The majority of these patients had rapid gastric emptying, but a smaller subset had delayed gastric emptying.

    “The majority of these patients had rapid gastric emptying, but a smaller subset had delayed gastric emptying (87);”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [87] Loavenbruck, 2015, Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome, Neurogastroenterol Motil source

      The Results (Demographic Features, Clinical Characteristics and Gastrointestinal Transit) report rapid gastric emptying in 78 of 163 patients (48%) and delayed emptying in 30 (18%). Rapid emptying was the most common finding, but 48% is not a majority of all patients. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Patient quality of life improved after exercise training but not with propranolol treatment.

    “Patient quality of life also improved after exercise training, but not with propranolol treatment (98).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [98] Fu, 2011, Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome, Hypertension source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Chronic fatigue has been cited in up to 48% of POTS patients, and patients with CFS often have POTS as well.

    “Chronic fatigue has been cited in up to 48% of POTS patients (6), and patients with CFS often have POTS as well (81).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [6] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source
    • cites [81] Miwa, 2008, Small heart syndrome in patients with chronic fatigue syndrome, Clin Cardiol source

      Citation (81) is attached to the claim that patients with CFS often have POTS; the 48% figure is attached to a different citation. The Physical Examination Findings (p. 330) report orthostatic dizziness in some patients with CFS, but our copy does not identify it as POTS or report POTS prevalence. Searches for “POTS” and “orthostatic tachycardia” found no passage establishing the claimed overlap. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The majority of patients who complete the exercise training program no longer meet criteria for POTS, and the vast majority, if not all, report improved quality of life using a reliable and valid questionnaire.

    “The majority of patients who complete the exercise training program no longer meet criteria for POTS, and the vast majority, if not all patients, report improved quality of life using a reliable and valid questionnaire (4,101).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [4] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol source

      The Results (Exercise training effects; page unavailable) report that 10 of 19 completers no longer met POTS criteria and that quality of life improved after training. The Methods identify the questionnaire as the SF-36, but our copy does not establish the claim that it is reliable and valid. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [101] Galbreath, 2011, Effects of exercise training on arterial-cardiac baroreflex function in POTS, Clin Auton Res source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Clonidine can be used to reduce autonomic instability in similar patients.

    “Clonidine (a central sympatholytic) 0.1 mg twice daily can be used to reduce autonomic instability in similar patients (36).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [36] Low, 2009, Postural tachycardia syndrome (POTS), J Cardiovasc Electrophysiol source

  • May combine two claims.

    Premisecitation

    Pyridostigmine can increase parasympathetic autonomic tone and has a lower risk of hypertension compared with other medications.

    “Pyridostigmine (a cholinergic agonist that works by inhibiting acetylcholinesterase) 30 to 60 mg 3 times a day can increase parasympathetic autonomic tone (107,108) and has a lower risk of hypertension compared with other medications.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [107] Raj, 2005, Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome, Circulation source
    • cites [108] Kanjwal, 2011, Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience, Pacing Clin Electrophysiol source

  • May combine two claims.

    Premisecitation

    The supine hypertension that accompanies NOH leads to increased nocturnal diuresis, which in turn worsens orthostatic intolerance, particularly in the morning.

    “the supine hypertension that accompanies NOH leads to increased nocturnal diuresis, which in turn worsens orthostatic intolerance, particularly in the morning.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [106] Gibbons, 2017, The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension, J Neurol source

  • May combine two claims.

    Premisecitation

    In a double-blind drug trial, propranolol was effective at reducing standing HR, but exercise training was superior to propranolol at restoring upright hemodynamics and normalizing renal-adrenal responsiveness.

    “Even though propranolol was also effective at reducing standing HR, exercise training was found to be superior to propranolol at restoring upright hemodynamics and normalizing renal-adrenal responsiveness.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [98] Fu, 2011, Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome, Hypertension source

  • May combine two claims.

    Premisecitation

    Although long-acting propranolol has been demonstrated to reduce standing HR in POTS, this medication did not improve quality of life.

    “However, although long-acting propranolol has been demonstrated to reduce standing HR in POTS, this medication did not improve quality of life (98).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [98] Fu, 2011, Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome, Hypertension source

  • Classified as probably not a substantial claim.

    Premisecitation

    A regular, structured, progressive exercise program is a Heart Rhythm Society Class IIa recommendation for the treatment of POTS.

    “A regular, structured, and progressive exercise program is a Heart Rhythm Society (HRS) Class IIa recommendation for the treatment of POTS, and it may receive enhanced recommendation based on recent data and lack of other proven effective therapies (1).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Sheldon, 2015, 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source

      The POTS Treatment section recommends a regular, structured, graduated exercise program, supporting the exercise recommendation. The passages in our copy do not state its HRS recommendation class, so the specific Class IIa designation is not verified. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In POTS patients, the mean age is 30.2 ± 10.3 years and 86% are women.

    “The typical demographic is young women (mean age 30.2 Æ 10.3 years, 86% women)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    POTS affects an estimated 500,000 Americans based on a 1999 report.

    “affecting an estimated 500,000 Americans based on a 1999 report (2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Robertson, 1999, The epidemic of orthostatic tachycardia and orthostatic intolerance, Am J Med Sci source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The prevalence of POTS may have increased over the past 2 decades due to increased awareness of the syndrome.

    “due to increased awareness of the syndrome, the prevalence of POTS may have increased over the past 2 decades.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    Not all patients with orthostatic intolerance have POTS, though all patients with POTS have symptoms of orthostatic intolerance.

    “Not all patients with orthostatic intolerance have POTS, though all patients with POTS have symptoms of orthostatic intolerance.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The onset of POTS can be subacute (13.8%), insidious (5.9%), or acute (12.5%).

    “The onset of POTS can be subacute (13.8%), insidious (5.9%), or acute (12.5%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source

  • May combine two claims.

    Interpretationreasoning

    Heat stress dramatically decreases orthostatic tolerance in healthy humans, and this is why orthostatic intolerance of all types, including POTS, is worsened by heat.

    “Heat stress dramatically decreases orthostatic tolerance in healthy humans, and this is why orthostatic intolerance of all types (including POTS) is worsened by heat.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Central blood volume plays a critical role in the acute regulation of the sympathetic nervous system; volume loading induces virtual sympathetic silence, and volume unloading causes marked sympathetic activation.

    “Central blood volume plays a critical role in the acute regulation of the sympathetic nervous system; volume loading induces virtual sympathetic silence, and volume unloading causes marked sympathetic activation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Pawelczyk, 2001, Regulation of muscle sympathetic nerve activity after bed rest deconditioning, Am J Physiol Heart Circ Physiol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    POTS is frequently preceded by symptoms of a viral illness (42%) or may occur post-operatively (9.5%).

    “It is frequently preceded by symptoms of a viral illness (in 42%) or may occur post-operatively (in 9.5%) (6).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Symptoms commonly associated with POTS may not be part of a single unifying underlying disease process or linked clearly by a common pathophysiology.

    “they may not be part of a single unifying, underlying disease process, or linked clearly by a common pathophysiology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Although the mechanisms have not specifically been shown to cause POTS, there are remarkable similarities between the effects of spaceflight/bedrest and POTS, which may be informative for considering POTS pathophysiology.

    “Though these mechanisms have not specifically been shown to “cause” POTS, there are remarkable similarities between the effects of spaceflight/bedrest and POTS, which may be informative in considering the potential pathophysiology of POTS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    The findings on lower-extremity blood flow POTS subgroups have not been demonstrated prospectively, and differentiating POTS subgroups based on lower extremity blood flow has not been shown to lead to unique therapies.

    “However, these findings have not been demonstrated prospectively, and differentiating POTS subgroups based on lower extremity blood flow have not been shown to lead to unique therapies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Regardless of the precipitating cause, the state of cardiovascular deconditioning often dominates the clinical picture and is a major cause of functional disability.

    “Ultimately, regardless of the precipitating cause, the state of cardiovascular deconditioning often dominates the clinical picture and is a major cause of functional disability (26).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Raj

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In a cohort study of unselected POTS patients, the prevalence of ganglionic AChR antibodies (always at low antibody levels) was <5%, and this antibody frequency was not statistically different from population controls.

    “In a cohort study of unselected POTS patients, the prevalence of ganglionic AChR antibodies (always at low antibody levels) was <5%, and this antibody frequency was not statistically different from population controls (48,49).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [48] Vernino, 2015, Prevalence of ganglionic AChR antibodies in postural tachycardia syndrome (POTS) (abstr), Neurology source
    • cites [49] Vernino S, Bryarly M, Hopkins S, et al. The prevalence of galgnion AChR antibodies in postural tachycardia syndrome (POTS). Paper presented at: 27th International Symposium on the Autonomic Nervous System; November 3, 2016; San Diego, CA.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Study design and conductnone given

    The finding on nondipping POTS patients has not yet been reproduced, and its significance is currently unclear.

    “This finding has not yet been reproduced, however, and its significance is currently unclear.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    By contrast, the tachycardia in POTS is triggered by orthostatic stress, and POTS patients usually have a normal resting supine HR.

    “By contrast, the tachycardia in POTS is triggered by orthostatic stress, and POTS patients usually have a normal resting supine HR.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Inappropriate sinus tachycardia is sometimes confused with POTS, but occurs independent of body position.

    “Inappropriate sinus tachycardia (IST) is sometimes confused with POTS, but occurs independent of body position (66).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Pellegrini, 2016, Epidemiology and definition of inappropriate sinus tachycardia, J Interv Card Electrophysiol source

  • May combine two claims.

    Premisereasoning

    Neurally mediated syncope is not synonymous with POTS and is a separate problem, but NMS can lead to similar symptoms of orthostatic intolerance particularly in the immediately pre-syncopal phase.

    “Neurally mediated syncope (NMS) (“vasovagal” or reflex) syncope is not synonymous with POTS and is a separate problem, but NMS can lead to similar symptoms of orthostatic intolerance particularly in the immediately pre-syncopal phase.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Up to 30% of POTS patients may experience syncope, and these patients may have both NMS and POTS, because these disorders can occur together.

    “However, up to 30% of POTS patients may experience syncope, and these patients may have both NMS and POTS, because these disorders can occur together (9,65).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Raj, 2006, The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & management, Indian Pacing Electrophysiol J
    • cites [65] Ojha, 2011, Comorbidities in pediatric patients with postural orthostatic tachycardia syndrome, J Pediatr source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Sinus tachycardia is usually a normal physiological response to conditions in which the sympathetic nervous system is activated and the parasympathetic nervous system is inhibited, such as exercise, fever/infection, anemia, anxiety, and pain.

    “Sinus tachycardia is usually a normal physiological response to conditions in which the sympathetic nervous system is activated and the parasympathetic nervous system is inhibited, such as exercise, fever/ infection, anemia, anxiety, and pain.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Orthostatic tachycardia alone is not sufficient to diagnose POTS; other diagnostic criteria apply, and other syndromes and intrinsic cardiac abnormalities must be excluded.

    “Orthostatic tachycardia alone is not sufficient to diagnose POTS; other diagnostic criteria apply, and other syndromes and intrinsic cardiac abnormalities must be excluded.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The tachycardia of POTS is a sinus tachycardia.

    “The tachycardia of POTS is a sinus tachycardia.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Similarly to patients with POTS, patients with neurogenic orthostatic hypotension can also complain of orthostatic intolerance.

    “Similarly to patients with POTS, patients with neurogenic orthostatic hypotension (NOH) can also complain of orthostatic intolerance.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Evaluation for pheochromocytoma is best made by measuring plasma metanephrines.

    “Evaluation for pheochromocytoma is best made by measuring plasma metanephrines (67).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Lenders, 2002, Biochemical diagnosis of pheochromocytoma: which test is best?, JAMA source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    Acute or chronic hypovolemia may be associated with orthostatic sinus tachycardia, with or without accompanying orthostatic hypotension, as stroke volume falls and HR increases to maintain cardiac output and oxygen delivery to tissue.

    “Acute or chronic hypovolemia may be associated with orthostatic sinus tachycardia, with or without accompanying orthostatic hypotension, as stroke volume falls and HR increases to maintain cardiac output and oxygen delivery to tissue.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Only a single case report has been described of a woman with POTS who had both symptoms and urodynamic evidence of detrusor hyperreflexia; other data providing objective evidence of urinary dysfunction in POTS patients are lacking.

    “Only a single case report has been described of a woman with POTS who had both symptoms and urodynamic evidence of detrusor hyperreflexia (91); other data providing objective evidence of urinary dysfunction in POTS patients are lacking.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [91] O'Leary, 2002, Neurovesical dysfunction in postural tachycardia syndrome (POTS), Int Urogynecol J Pelvic Floor Dysfunct source

  • May combine two claims.

    Interpretationreasoning

    Joint hypermobility may not be pathophysiologically important for the development of orthostatic intolerance in POTS patients; rather it may be another comorbid condition that occurs in patients with chronic functional disorders.

    “This suggests that joint hypermobility may not be pathophysiologically important for the development of orthostatic intolerance in POTS patients; rather it may be another comorbid condition that occurs in patients with chronic functional disorders (71).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Chelimsky, 2016, Benign joint hypermobility minimally impacts autonomic abnormalities in pediatric subjects with chronic functional pain disorders, J Pediatr source

  • May combine two claims.

    Premisecitation

    A frequently described comorbidity in POTS patients is migraine, as well as other chronic headache types.

    “A frequently described comorbidity in POTS patients is migraine, as well as other chronic headache types (6,65,72,73).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [6] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source
    • cites [65] Ojha, 2011, Comorbidities in pediatric patients with postural orthostatic tachycardia syndrome, J Pediatr source
    • cites [72] Mack, 2010, Orthostatic intolerance and the headache patient, Semin Pediatr Neurol source
    • cites [73] Qubty, 2016, Dizziness and orthostatic intolerance in pediatric headache patients, Semin Pediatr Neurol source

  • May combine two claims.

    Interpretationcitation

    An exaggerated sympathetic vasoconstrictor response during the Valsalva maneuver or the presence of orthostatic hypertension may suggest hyperadrenergic POTS.

    “An exaggerated sympathetic vasoconstrictor response during the Valsalva maneuver or the presence of orthostatic hypertension may suggest hyperadrenergic POTS (46).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Shibao, 2005, Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders, Hypertension source

  • May combine two claims.

    Premisecitation

    Exercise therapy is most successful when the program is supervised by experienced trainers or physical therapists that understand the pathophysiology of POTS, though it has also been demonstrated to be highly effective when administered in a community setting.

    “Exercise therapy is most successful when the program is supervised by experienced trainers or physical therapists that understand the pathophysiology of POTS, though it has also been demonstrated to be highly effective when administered in a community setting (64).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] George, 2016, The international POTS registry: Evaluating the efficacy of an exercise training intervention in a community setting, Heart Rhythm source

  • May combine two claims.

    Premisecitation

    These measures increase venous return and lessen orthostatic tachycardia.

    “These measures increase venous return and lessen orthostatic tachycardia (105).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [105] Smit, 2004, Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction, Clin Auton Res source

  • May combine two claims.

    Premisecitation

    This effect, however, is transient, and ultimately results in a net loss of plasma volume following the infusion.

    “This effect, however, is transient, and ultimately results in a net loss of plasma volume following the infusion (104).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [104] Heer, 1992, Effects of head-down tilt and saline loading on body weight, fluid, and electrolyte homeostasis in man, Acta Physiol Scand Suppl

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Nonorthostatic comorbid symptoms and conditions may persist even after the orthostatic tachycardia is treated.

    “Nonorthostatic comorbid symptoms and conditions may persist even after the orthostatic tachycardia is treated.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Many symptoms occur independently of POTS, and others persist even after the resolution of postural intolerance.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    POTS is a heterogeneous disorder with many overlapping symptoms and pathophysiological mechanisms.

    “POTS is a heterogeneous disorder with many overlapping symptoms and pathophysiological mechanisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The most effective treatment for POTS is a regular, structured, progressive exercise regimen, enhanced by volume expansion with ingested salt and fluids.

    “The most effective treatment is a regular, structured, progressive exercise regimen, enhanced by volume expansion with ingested salt and fluids.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Concussion has been associated with development of POTS, and there is a relatively high rate of POTS in patients with persistent post-concussive syndrome.

    “Concussion has also been associated with development of POTS, and there is a relatively high rate of POTS in patients with persistent post-concussive syndrome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Even when deconditioning does not seem to be a large factor in the development of POTS, exercise training can still be useful in its treatment by improving fitness and reducing pain and hypervigilance through well-defined neural mechanisms.

    “Even in cases where deconditioning does not seem to be a large factor in the development of POTS, it can still be useful in its treatment by improving fitness, and reducing pain and hypervigilance through welldefined neural mechanisms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Sport-related concussion has been reported to affect postural stability and neurocognitive function.

    “Sport-related concussion has been reported to affect postural stability as well as neurocognitive function(74).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Guskiewicz, 2001, Postural stability assessment following concussion: one piece of the puzzle, Clin J Sport Med source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Standard evaluations for POTS include laboratory, physical examination, and simple stand test.

    “Standard evaluations include laboratory, physical examination, and simple stand test.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    The most common demographic of POTS is young, previously active women, and frequently an identifiable event such as illness, pregnancy, or surgery precedes symptom onset and precipitates withdrawal of activity or frank bedrest.

    “The most common demographic is young, previously active women, and frequently, there is an identifiable event (such as illness, pregnancy, or surgery) that precedes symptom onset and precipitates withdrawal of activity or frank bedrest.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Intractable migraines often lead to physical inactivity, which may exacerbate orthostatic intolerance, and increased sympathetic activity associated with POTS may contribute to increased frequency of headaches.

    “Intractable migraines often lead to physical inactivity, which may exacerbate orthostatic intolerance, and conversely, the increased sympathetic activity associated with POTS may contribute to increased frequency of headaches.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Perceptual amplification and hypervigilance are phenomena described in chronic pain conditions like fibromyalgia.

    “Perceptual amplification and hypervigilance are phenomena described in chronic pain conditions, like fibromyalgia.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (76)(77)(78)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationnone given

    POTS cardinal symptoms occur with standing and improve with sitting or lying, but patients often have other chronic symptoms and comorbidities that cannot be physiologically explained by orthostatic intolerance or tachycardia.

    “Although the cardinal symptoms of POTS occur with standing and improve with sitting or lying, patients often relate other chronic symptoms and comorbidities that cannot physiologically be explained by orthostatic intolerance or tachycardia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Perceptual amplification and hypervigilance are associated with increased sensitivity and aversion toward somatic signals, tactile stimuli, and pain, and an increased propensity to report sensations that others might ignore.

    “They are associated with an increased sensitivity and aversion toward somatic signals, tactile stimuli, and pain, with an increased propensity to report sensations that others might ignore(76)(77)(78).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (76)(77)(78)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Droxidopa has been studied in a small number of POTS patients; although it may have helped to improve some symptoms of orthostatic intolerance, it did not significantly improve quality of life.

    “Droxidopa has been studied in a small number of POTS patients; although it may have helped to improve some symptoms of orthostatic intolerance, it did not significantly improve quality of life (111).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Ruzieh, 2017, Droxidopa in the treatment of postural orthostatic tachycardia syndrome, Am J Ther source

  • May combine two claims.

    Interpretationnone given

    The conditions associated with POTS are not core features of, nor synonymous with, POTS; they are syndromes that may occur together with POTS.

    “Specifically, the following described conditions are not core features of, nor are they synonymous with, POTS.Rather, these are syndromes that may occur together with POTS (Figure4).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Other nonpharmacological and pharmacological interventions may be supplemental in POTS treatment.

    “Other nonpharmacological and pharmacological interventions may be supplemental.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Although anxiety is commonly described in POTS, the excessive tachycardia is not simply a physiological manifestation of anxiety.

    “Although anxiety is a commonly described in POTS, the excessive tachycardia is not simply a physiological manifestation of anxiety(80).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] Masuki, 2007, Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety, J Appl Physiol source

  • May combine two claims.

    Interpretationcitation

    The resolution of POTS often runs parallel with the resolution of postconcussive syndrome, likely reflecting the patient's return to physical activity.

    “The resolution of POTS often runs parallel with the resolution of postconcussive syndrome (75) likely reflecting the patient's return to physical activity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Heyer, 2016, Orthostatic intolerance and autonomic dysfunction in youth with persistent postconcussion symptoms: a head-upright tilt table study, Clin J Sport Med source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    An active stand test is a simple evaluation for POTS and orthostatic hypotension that can be done at the bedside or in the clinic with only an automated or manual BP cuff.

    “An active stand test is a simple evaluation for POTS (and orthostatic hypotension) that can be done at the bedside or in the clinic with only an automated or manual BP cuff.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Specific data supporting psychological therapy in POTS are lacking, but there is a 2016 case report demonstrating significant decrease in POTS-related functional impairment in a woman treated with cognitive behavioral therapy.

    “Specific data supporting psychological therapy in POTS are lacking, but there is a 2016 case report demonstrating significant decrease in POTS-related functional impairment in a woman treated with cognitive behavioral therapy (116).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Ralston, 2016, Symptom discrimination and habituation: a case study of behavioral treatment for postural orthostatic tachycardia syndrome (POTS), Behav Med source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    The unifying characteristics of POTS are excessive tachycardia in the upright position, without orthostatic hypotension, and with associated presyncopal symptoms and orthostatic intolerance.

    “The unifying characteristics are excessive tachycardia in the upright position, without orthostatic hypotension, and with associated presyncopal symptoms and orthostatic intolerance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Behavioral and cognitive therapy may help POTS patients with significant associated symptoms such as anxiety, hypervigilance, and brain fog.

    “These symptoms can be challenging to treat, and behavioral and cognitive therapy may help patients with significant associated symptoms such as anxiety, hypervigilance, and brain fog.”
    Quote in the paperNot a substantial claim
72 of 72

  • The paper relies on this without support.

    A period of enforced bedrest is often a common theme in patients with POTS, even those who have previously been quite active.

    “Indeed, a period of enforced bedrest is often a common theme in patients with POTS, even those who have previously been quite active.”

  • The paper relies on this without support.

    In many cases, patients with POTS relate a healthy and active premorbid state; some are competitive athletes or high-performing high school or college students before developing POTS.

    “In many cases, patients relate a healthy and active premorbid state; some are competitive athletes or high-performing high school or college students before developing POTS.”

  • The paper relies on this without support.

    POTS is quite rare after menopause.

    “It is our experience that POTS is quite rare after menopause, though explanations for this age specificity are unsatisfying.”

  • The authors state this as an assumption.

    Underlying hormonal changes, presumably relating to the balance between testosterone and estrogen, play a role in the age specificity of POTS.

    “The underlying hormonal changes, presumably relating to the balance between testosterone and estrogen, must be playing a role.”

  • The paper relies on this without support.

    The current epidemiology of POTS is not known.

    “The current epidemiology is not known, but due to increased awareness of the syndrome, the prevalence of POTS may have increased over the past 2 decades.”

  • The paper relies on this without support.

    The pathophysiology and mechanisms of POTS are not well understood.

    “This is a heterogeneous disorder, the pathophysiology and mechanisms of which are not well understood.”

  • The paper relies on this without support.

    These tests (provocative medications during HUT) unmask NMS in addition to evoking syncope in several other conditions, including many normal individuals, and are very nonspecific.

    “In actuality, these tests unmask NMS in addition to evoking syncope in several other conditions, including many normal individuals, and recent studies have shown these tests to be very nonspecific.”

  • The paper relies on this without support.

    Environmental heat, prolonged upright posture, prolonged fasting, excessive alcohol intake, straining, or vasodilatory medications will exacerbate orthostatic intolerance.

    “Environmental heat, prolonged upright posture, prolonged fasting, excessive alcohol intake, straining (such as during urination or bowel movements), or vasodilatory medications will exacerbate orthostatic intolerance and should be avoided when possible.”

  • The paper relies on this without support.

    Chronic fatigue and fibromyalgia often lead to a reduction in physical activity, subsequent deconditioning, and exacerbation of orthostatic intolerance.

    “Furthermore, chronic fatigue and fibromyalgia often lead to a reduction in physical activity, subsequent deconditioning, and exacerbation of orthostatic intolerance.”

  • The paper relies on this without support.

    Patients with hyperadrenergic POTS may have elevated NE levels (typically >600 to 1,000 pg/ml).

    “Patients with hyperadrenergic POTS may have elevated NE levels (typically >600 to 1,000 pg/ml).”

  • The paper relies on this without support.

    Plasma tryptase may be elevated in these individuals during symptomatic episodes.

    “Plasma tryptase may be elevated in these individuals during symptomatic episodes.”

  • The paper relies on this without support.

    N-methylhistamine >230 mg/g creatinine in a 4-h urine collection immediately following a spontaneous event would also be suggestive of this disorder.

    “N-methylhistamine >230 mg/g creatinine in a 4-h urine collection immediately following a spontaneous event would also be suggestive of this disorder.”

  • The paper relies on this without support.

    In the majority of cases, POTS can be diagnosed and managed by primary care physicians.

    “In the majority of cases, POTS can be diagnosed and managed by primary care physicians.”

  • The paper relies on this without support.

    POTS often can be managed by nonpharmacological measures alone.

    “POTS often can be managed by nonpharmacological measures alone.”

  • The paper relies on this without support.

    These strategies can help increase blood volume and minimize orthostatic symptoms.

    “These strategies can help increase blood volume and minimize orthostatic symptoms.”

  • The paper relies on this without support.

    In MCAD, inappropriate release of histamine and other mast cell mediators in response to physical activity or orthostatic stress may lead to orthostatic tachycardia.

    “In mast cell activation disorder (MCAD), inappropriate release of histamine and other mast cell mediators in response to physical activity or orthostatic stress may lead to orthostatic tachycardia.”

  • The paper relies on this without support.

    MCAD patients may have POTS with hyperadrenergic features (increased HR and BP with standing).

    “MCAD patients may have POTS with hyperadrenergic features (increased HR and BP with standing).”

  • The paper relies on this without support.

    Abrupt withdrawal of beta-blockers or central sympatholytic agents such as clonidine may cause rebound tachycardia.

    “Abrupt withdrawal of certain medications such as beta-blockers or central sympatholytic agents such as clonidine, may also cause rebound tachycardia.”

  • The paper relies on this without support.

    Many symptoms occur independently of POTS, and others persist even after the resolution of postural intolerance.

    “Many symptoms occur independently of POTS, and others persist even after the resolution of postural intolerance.”
19 of 19

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.

  • Conflicting adolescent heart-rate threshold

    Minor

    The prose says the heart-rate increment must exceed 40 beats/min for patients under 20, whereas Figure 1 says an increment of at least 40 bpm qualifies for ages 12 to 19. They disagree at exactly 40 bpm.

  • Conflicting criteria for orthostatic hypotension

    Minor

    The text defines orthostatic hypotension as a systolic drop of at least 20 mm Hg and/or a diastolic drop of at least 10 mm Hg. Figure 1 instead excludes only a systolic drop greater than 20 mm Hg. The definitions disagree for a diastolic-only drop and for a systolic drop of exactly 20 mm Hg, affecting who meets the stated POTS criteria.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Vernino S, Bryarly M, Hopkins S, et al. The prevalence of galgnion AChR antibodies in postural tachycardia syndrome (POTS). Paper presented at: 27th International Symposium on the Autonomic Nervous System; November 3, 2016; San Diego, CA.
  2. Gibbons, 2011, Intense cardiovascular exercise as a treatment for postural tachycardia syndrome (POTS) (abstr), Neurology, 76, A264

Cited by

Sorted by citations

Related

Authors
Bryarly, M., Phillips, L. T., Fu, Q., Vernino, S., & Levine, B. D.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Texas Health Dallas (US)
Corresponding author
Levine, Benjamin D.
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2019-03
Volume
73
Issue
10
Pages
1207-1228
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2018.11.059
OpenAlex
W2921285569
Semantic Scholar
740ef6a8cee1d3f390f8ab74aa520e3c99885859
Cited by
245
References
116
Citations by year
2026: 34 · 2025: 38 · 2024: 38 · 2023: 28 · 2022: 41 · 2021: 34 · 2020: 26 · 2019: 6
FWCI
5.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Biogen
  • H. Lundbeck A/S
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (K23HL075283)
  • National Center for Research Resources (M01RR000633)
Topics
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
Keywords
postural orthostatic tachycardia syndrome, orthostatic intolerance, pathophysiology, comorbidities, differential diagnosis, evaluation, treatment, young women, autonomic dysfunction
MeSH terms
Diagnosis, Differential, Humans, Patient Care Management, Comorbidity, Causality, Postural Orthostatic Tachycardia Syndrome

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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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-31.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-31.

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