The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index; 11 of the 138 sources its claims cite were checked for support.
Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies
Abstract
Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension. The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Patients often will exhibit overlapping characteristics from more than one of these mechanisms. The approach to the treatment of POTS centers on treating the underlying pathophysiologic mechanism. Stockings, abdominal binders, and vasoconstrictors are used to enhance venous return in partial neuropathic POTS. Exercise and volume expansion are the main treatment strategies for hypo-volemic POTS. For hyperadrenergic POTS, beta-blockers and avoidance of norepinephrine reuptake inhibitors is important. Attempts should be made to discern which pathophysiologic mechanism(s) may be afflicting patients so that treatment regimens can be individualized.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder defined by an upright heart rate increase of at least 30 bpm without orthostatic hypotension, with three major overlapping pathophysiologic endophenotypes: partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Treatment should be individualized to the underlying mechanism(s), using nonpharmacologic and pharmacologic strategies such as compression, volume expansion, exercise, beta-blockers, and avoidance of norepinephrine reuptake inhibitors.
Key findings
- POTS is estimated to affect 0.5–3 million individuals in the United States; >90% of patients are young, white women of childbearing age, and symptoms must persist for at least 3–6 months without another chronic condition or medication causing orthostatic intolerance.
- The three major endophenotypes are neuropathic POTS (partial autonomic neuropathy with lower-extremity, pelvic, and splanchnic blood pooling), hypovolemic POTS (13–22% lower plasma or blood volume, renin-aldosterone paradox, and Ang-II levels 2–3 times higher in some patients), and hyperadrenergic POTS (upright plasma norepinephrine often exceeding 800 pg/ml versus approximately 400–500 pg/ml in healthy controls).
- Treatment is mechanism-targeted: midodrine 5–10 mg acutely reduced heart rate from 108 bpm to 95 bpm in 13 POTS patients; 3 months of exercise training led 50–70% of completers to no longer meet POTS criteria, though only 41% of community patients completed a standardized program; hyperadrenergic POTS treatment includes beta-blockers, pyridostigmine, ivabradine, and avoidance of NRIs, SSRIs, or SNRIs.
- Patients often exhibit overlapping features from more than one endophenotype, and no single all-unifying pathophysiologic mechanism exists; POTS may be a final common pathway for several interrelated mechanisms.
Methods
- Narrative review of the literature on POTS mechanisms and therapies; no primary data collection, systematic search strategy, or meta-analysis is described.
- Synthesizes prior studies into three pathophysiologic endophenotypes and a treatment table, citing small prospective studies, randomized trials, retrospective analyses, and case series.
- Main analysis is qualitative mechanistic and therapeutic synthesis rather than formal quantitative analysis.
Limitations
- Stated in the paper: the exact prevalence of POTS is unknown; an all-inclusive pathophysiologic mechanism remains elusive; treatment knowledge has advanced mainly through small prospective studies; some agents are not well studied in POTS (e.g., fludrocortisone, droxidopa, ivabradine lacks a prospective comparator study); and exercise adherence is limited, with only 41% completing a standardized 3-month program.
- Evident from the text: as a narrative review, it does not systematically assess study quality, risk of bias, or publication bias, and many cited studies are small, retrospective, uncontrolled, or case series.
- Evident from the text: findings from special populations (e.g., astronauts, cosmonauts, Ehlers-Danlos syndrome patients, children) may not generalize to all POTS patients, and recommendations rely on synthesis and expert opinion rather than new empirical data.
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
89 Not checked yet · 12 Own interpretation · 5 Partly supported · 2 No basis given · 1 Supported · 1 Not supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While many conditions, such as mast cell activation disorders (9), Ehlers-Danlos syndrome (10, 11), deconditioning (12), and genetic mutations of norepinephrine transporters (13), coexist with POTS, their downstream effects also funnel into these three principal pathophysiologic mechanisms.”
What the sources say
- Not checked yetcites [9] source
- Not checked yetcites [10] source
- Partly supportedcites [11] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Neuronal nitrous oxide synthase, and not endothelial nitrous oxide synthase, was determined to be responsible for causing this phenomenon (29).”
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says selective nNOS inhibition blunted the local-heating response and that reduced nNOS-derived nitric oxide appears to account for the NO deficit in low-flow POTS, while eNOS function appears intact. These are qualified interpretations, not a determination that nNOS alone causes the phenomenon or that eNOS has no role. (LLM, conf=0.82)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Other studies have also demonstrated that POTS patients have significantly greater decreases in thoracic and cerebral blood flow when compared to healthy controls during tilt (21, 23, 25-27).”
What the sources say
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that thoracic blood flow decreased during tilt in all subjects and that thoracic blood volume was significantly smaller in POTS patients than in controls at 35° and 70°. They do not establish a significantly greater decrease in thoracic blood flow in POTS patients, and the paper does not report cerebral blood flow during tilt. (LLM, conf=0.85)
- Partly supportedcites [23] sourceExperimental — accuracy not yet measured
The Upright Tilt Data results report a significantly reduced change in central blood volume in all POTS groups, but this is a measure of volume, not thoracic blood flow. They also report significantly decreased cerebral blood flow velocity during tilt only in the POTS-hyperventilation group, not in all POTS patients. (LLM, conf=0.88)
- Not checked yetcites [25] source
- Partly supportedcites [26] sourceExperimental — accuracy not yet measured
The HUT With Transcranial Doppler results report a significant decrease in cerebral blood-flow velocity during tilt in patients with idiopathic orthostatic intolerance. The paper does not establish that this decrease was greater than in healthy controls, and it does not report thoracic blood flow. Its Discussion also cautions that Doppler measures flow velocity rather than blood flow directly; page numbers are unavailable in our copy. (LLM, conf=0.88)
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
The Results (page unavailable) report a significantly greater decrease in cerebral blood-flow velocity during tilt in POTS subjects than in controls (19.5% versus 10.3%, P < 0.05). The paper does not report a corresponding comparison of thoracic blood flow, so it supports only the cerebral part of the claim. The Methods limit the studied POTS group to young, normocapnic subjects. (LLM, conf=0.90)
boostedcorrelational- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“POTS patients will sometimes manifest features from more than one of the three major POTS endophenotypes (4).”
What the sources say
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
In “Need to Better Understand the Pathophysiologies Underlying POTS” (page unavailable), the paper says multiple underlying mechanisms can lead to POTS and several comorbid diagnoses can coexist in one patient. It does not identify three major POTS endophenotypes or state that patients manifest features of more than one; it instead calls for agreed-upon criteria for endophenotypes. (LLM, conf=0.81)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Not surprisingly, midodrine has been shown to be more effective in treating neuropathic POTS than hyperadrenergic POTS (56).”
What the sources say
- Supportedcites [56] source
The Discussion (Main findings; page not provided) reports that midodrine improved postural tachycardia versus placebo in neuropathic POTS but not hyperadrenergic POTS. The Summary and practical significance likewise says hyperadrenergic subjects responded similarly to midodrine and placebo. (LLM, conf=0.94)
boosteddirect- 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.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients often will exhibit overlapping characteristics from more than one of these mechanisms.”
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.
In the paper
“Jacob et al. (18) demonstrated significantly impaired sympathetic nervous system activity in the lower extremities of POTS patients.”
What the sources say
- Not checked yetcites [18] source
boostedcorrelational- 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.
In the paper
“In contrast, the amounts of norepinephrine released in the upper extremities in response to the same stimuli were no different between POTS patients and healthy controls.”
What the sources say
- Not checked yetcites [18] source
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state.”
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Stewart et al. (14-17) noted that pediatric patients with POTS had excessive pooling of blood in the lower extremities, primarily due to arteriolar dysregulation rather than inappropriately increased venous capacitance.”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 30
- Probably not a substantial claim. 4
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“This cutaneous vasodilation is mediated by nitric oxide, as the addition of a nitric oxide synthase inhibitor blunts the vasodilation in both POTS patients and healthy controls to the same degree.”
What the sources say
- Disputedcites [28] sourceExperimental — accuracy not yet measured
The Results (Cutaneous Hyperemia and Endothelial Dysfunction) report that L-NAME blunted the thermal-hyperemia plateau in reference subjects but did not substantially affect the already attenuated plateau in a low-flow POTS patient; the grouped data confirmed this pattern. Normal-flow POTS responses were similar to reference responses, so the paper does not find the same degree of blunting across POTS patients and controls. (LLM, conf=0.92)
Checked by a reasoning model — may be wrong.
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.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Exercise is the only intervention that has been shown to improve the aldosterone:renin ratio and increase plasma and blood volumes chronically (64).”
What the sources say
- Partly supportedcites [64] sourceExperimental — accuracy not yet measured
The Results (Exercise Training; page unavailable) report that three months of training increased plasma and blood volumes and modestly increased the aldosterone-to-renin ratio in POTS patients. The Results (Propranolol Treatment; page unavailable) report neither change with propranolol. The paper compares exercise with propranolol and placebo, so it does not establish that exercise is the only intervention capable of these effects. (LLM, conf=0.88)
boosteddirect- 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.
- Partly supported
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
“Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension.”
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
“POTS should not be considered a disease but a clinical syndrome or phenotype, with the aforementioned signs (orthostatic tachycardia) and symptoms that worsen and improve with posture change.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“Mast cell degranulation causes a variety of vasoactive substances (histamine, prostaglandins, platelet-activating factor) to be released into the circulation, potentially causing excessive vasodilation and blood pooling in the lower extremities (31).”
What the sources say
- Not checked yetcites [31] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Under normal gravitational conditions, two weeks of strict bedrest resulted in a 17% reduction in plasma volume and a near 10% reduction in stroke volume (41).”
What the sources say
- Not checked yetcites [41] source
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.
In the paper
“This intolerance primarily manifests as excessive orthostatic tachycardia and reduced QSART (cholinergic sympathetic nerve sweat testing) responses when compared to those of healthy controls (30).”
What the sources say
- Not checked yetcites [30] source
plaincorrelationaln = 39- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another study in 18 cosmonauts, who had spent several months on a space station, demonstrated that previously healthy individuals can experience moderate hemodynamic changes that almost meet some POTS criteria (average orthostatic heart rate increase by 26 bpm in the absence of orthostatic hypotension), with one individual meeting the orthostatic tachycardia criterion (heart rate increase by 31 b”
What the sources say
- Not checked yetcites [40] source
boostedcorrelational- 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
“Administration of atomoxetine, a selective norepinephrine reuptake inhibitor (NRI), significantly increased the standing heart rate (from 105 bpm to 121 bpm) in POTS patients and resulted in greater symptoms of orthostatic intolerance (46).”
What the sources say
- Not checked yetcites [46] source
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.
In the paper
“Time to peak concentration is 1 h after administration, and pharmacologic effects last 4-5 h (55).”
What the sources say
- Not checked yetcites [55] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Iatrogenic inhibition of the norepinephrine transporter has also been shown to engender a POTS-like state, increase upright heart rate, and exacerbate symptoms in POTS patients (46-49).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While it can reduce orthostatic tachycardia in POTS patients to a similar extent as midodrine, it lacks a widely available oral dosage form and must be administered subcutaneously (60, 61).”
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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, levels of norepinephrine in POTS patients can increase more than threefold, exceeding 800 pg/ml in many cases, while the increase in healthy controls after assuming an upright position is much more modest at approximately 400-500 pg/ml (36, 43).”
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.
In the paper
“Shannon et al. (13) discovered a single missense mutation (ALA457Pro) in the norepinephrine transporter gene ( SLC6A2 ) that resulted in a 98% loss of function in the transporter and was present in two identical twins with POTS.”
What the sources say
- Not checked yetcites [13] source
plaindirectn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Administration of a selective serotonin reuptake inhibitor (SSRI), sertraline, also appeared to acutely worsen symptoms in POTS patients, possibly due to nonselective inhibition of the norepinephrine transporter (47).”
What the sources say
- Not checked yetcites [47] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Although this elevated norepinephrine state may be secondary to partial autonomic neuropathy or hypovolemia, the hallmark of this endophenotype is primary adrenergic excess.”
hedgeddirect- 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
“Droxidopa is an orally active, synthetic prodrug of norepinephrine that reaches peak plasma concentration in 2 h (57).”
What the sources say
- Not checked yetcites [57] source
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.
In the paper
“Moreover, this dose did not cause hypertension nor significantly elevate blood pressure in this patient population (54).”
What the sources say
- Not checked yetcites [54] source
plainn = 13- 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
“Regardless, the renin-aldosterone paradox and dysregulation of RAAS play a central role in the pathogenesis of this POTS endophenotype, and clearly would be worsened in the setting of any deconditioning, either voluntary or imposed.”
boosteddirect- 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.
- Rests on an assumption: Ang-II is the major effector of the RAAS axis, causing systemic vasoconstriction, raising blood pressure, promoting fluid retention, and is critical for maintaining fluid balance homeostasis through aldosterone secretion.
In the paper
“In healthy subjects, the supine plasma norepinephrine level is approximately 200 pg/ml, and upon standing, it doubles before it plateaus after 7.5 min (43).”
What the sources say
- Not checked yetcites [43] source
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.
In the paper
“Each twin had normal levels of supine plasma norepinephrine (269 pg/ml and 199 pg/ml), but standing plasma norepinephrine exceeded 900 pg/ml.”
What the sources say
- Not checked yetcites [13] source
plainn = 2- 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
“Fedorowski et al. (44) demonstrated that these autoantibodies, in addition to acting like a direct beta-agonist, can also upregulate sympathetic nervous activity through allosteric interactions with the beta-receptors.”
What the sources say
- Not checked yetcites [44] source
boosteddirect- 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
“It has not been well studied prospectively, and a retrospective analysis demonstrated only modest improvement in symptoms (58).”
What the sources say
- Not checked yetcites [58] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“POTS patients who participated in and completed 3 months of exercise training garnered a significant reduction in orthostatic tachycardia and experienced significant increases in blood volume (42).”
What the sources say
- Not checked yetcites [42] source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“In these studies, doses were initiated at 2.5 mg orally once or twice daily, and titrated up to 10 mg twice daily based on response or side effects with response rates between 60% and 78% (83, 84).”
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The clinically heterogeneous nature of POTS makes management inherently difficult.”
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.
In the paper
“Patients also noted significant improvements in overall symptoms, specifically symptoms related to vision, tremulousness, and palpitations (69).”
What the sources say
- Not checked yetcites [69] source
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.
In the paper
“Raj et al. (78) demonstrated that the use of propranolol (instant release) at a 20 mg dose significantly reduced orthostatic tachycardia, and improved symptoms compared to placebo up to 4 h after administration.”
What the sources say
- Not checked yetcites [78] source
boosteddirect- 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
“Many also report encountering initial skepticism during presentation, being given an incorrect psychiatric diagnosis, and having seen more than ten doctors before the correct diagnosis was made (2).”
What the sources say
- Not checked yetcites [2] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“but it did improve symptoms, at the expense of elevating blood pressure, in one study of treatment-refractory POTS patients (72).”
What the sources say
- Not checked yetcites [72] source
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.
In the paper
“Pyridostigmine enhances cholinergic activity at both the ganglionic nicotinic and the postganglionic muscarinic acetylcholine receptors, with a likely net increase in parasympathetic nervous system tone (3).”
What the sources say
- Not checked yetcites [3] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Improving clinician awareness can help improve all of these shortcomings (4).”
What the sources say
- Not checked yetcites [4] source
plainconditional- 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.
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
“Lack of strong data and the high expense of erythropoietin limit its routine use in the treatment of POTS.”
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 relies on this without support.
Targeting the underlying pathophysiologic mechanism in POTS improves clinical outcomes.
“The approach to the treatment of POTS centers on treating the underlying pathophysiologic mechanism.”
The paper relies on this without support.
The three POTS endophenotypes can be reliably distinguished in individual patients so that treatment can be individualized.
“Attempts should be made to discern which pathophysiologic mechanism(s) may be afflicting patients so that treatment regimens can be individualized.”
The paper relies on this without support.
Ang-II is the major effector of the RAAS axis, causing systemic vasoconstriction, raising blood pressure, promoting fluid retention, and is critical for maintaining fluid balance homeostasis through aldosterone secretion.
“Ang-II is the major effector of the RAAS axis, causing systemic vasoconstriction, raising blood pressure, and promoting fluid retention, and it is critical for maintaining fluid balance homeostasis through aldosterone secretion.”
The paper relies on this without support.
Midodrine is efficacious in treating hypovolemic POTS.
“Although midodrine does not directly expand plasma volume, it has been shown to be quite efficacious in treating hypovolemic POTS.”
The paper relies on this without support.
Oral clonidine has a short half-life and can cause a rapid onset-rapid offset phenomenon in some patients.
“Oral clonidine has a short half-life and can cause a rapid onset-rapid offset phenomenon in some patients.”
The paper relies on this without support.
Methyldopa has a longer half-life than oral clonidine and is often better tolerated by POTS patients.
“Methyldopa has a longer half-life than oral clonidine and is often better tolerated by POTS patients.”
Citations
Cites
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Self-citationOrthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency
Shannon, J. R., Flattem, N. L., Jordan, J., Jacob, G., Black, B. K., Biaggioni, I., Blakely, R. D., & Robertson, D. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002243420803 · Cited by 594
Hunyady, L., & Catt, K. J. (2006) · Molecular Endocrinology · doi:10.1210/me.2004-0536 · Cited by 541
The neuropathic postural tachycardia syndrome
Jacob, G., Costa, F., Shannon, J. R., Robertson, R. M., Wathen, M., Stein, M., Biaggioni, I., Ertl, A., Black, B., & Robertson, D. (2000) · New England Journal of Medicine · doi:10.1056/nejm200010053431404 · Cited by 398
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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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“The majority (>90%) of POTS patients are young, white women of childbearing age (2).”
BackgroundSelf-citationPostural Tachycardia Syndrome (POTS)
Raj, S. R. (2013) · Circulation · doi:10.1161/circulationaha.112.144501 · Cited by 320
Self-citationThe epidemic of orthostatic tachycardia and orthostatic intolerance
Robertson, D. (1999) · The American Journal of the Medical Sciences · doi:10.1016/s0002-9629(15)40480-x · Cited by 293
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Cited by
Sorted by citations
Connelly‐Smith, L. S., Alquist, C. R., Aqui, N. A., Hofmann, J. C., Klingel, R., Onwuemene, O. A., Patriquin, C. J., Pham, H. P., Sanchez, A. P., Schneiderman, J., et al. (2023) · Journal of Clinical Apheresis · doi:10.1002/jca.22043 · Cited by 751
ASIA syndrome and endocrine autoimmune disorders
Bragazzi, N. L., Hejly, A., Watad, ., Adawi, M., Amital, H., & Shoenfeld, Y. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101412 · Cited by 134
Taub, P. R., Zadourian, A., Lo, H. C., Ormiston, C. K., Golshan, S., & Hsu, J. C. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.12.029 · Cited by 122
Raj, S. R., Bourne, K. M., Stiles, L. E., Miglis, M. G., Cortez, M. M., Miller, A. J., Freeman, R. L., Biaggioni, I., Rowe, P. C., Sheldon, R. S., et al. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102836 · Cited by 63
Self-citationEffect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome
Garland, E. M., Gamboa, A., Nwazue, V. C., Celedonio, J. E., Paranjape, S. Y., Black, B. K., Okamoto, L. E., Shibao, C. A., Biaggioni, I., Robertson, D., et al. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.03.005 · Cited by 65
Self-citationNoninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome
Stavrakis, S., Chakraborty, P., Farhat, K., Whyte, S., Morris, L. M., Asad, Z. U. A., Karfonta, B., Anjum, J., Matlock, H. G., Cai, X., et al. (2023) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2023.10.015 · Cited by 68
COVID-19 Induced Postural Orthostatic Tachycardia Syndrome (POTS): A Review
Mallick, D. C., Goyal, L., Chourasia, P. K., Zapata, M. R., Yashi, K., & Surani, S. (2023) · Cureus · doi:10.7759/cureus.36955 · Cited by 62
“Intravascular volume expansion by salt and water intake: It is suggested that patients with POTS should be encouraged to have a daily oral fluid intake of up to 3 L/day and sodium chloride of up to 8 to 12 g [63-65].”
BackgroundMalkova, A. M., & Shoenfeld, Y. (2022) · Autoimmunity Reviews · doi:10.1016/j.autrev.2022.103230 · Cited by 53
Postural Orthostatic Tachycardia Syndrome (POTS): An Update for Clinical Practice
Sebastian, S. A., Co, E. L., Panthangi, V., Jain, E., Ishak, A., Shah, Y., Vasavada, A. M., & Padda, I. (2022) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2022.101384 · Cited by 41
Tsuchida, T., Yoshimura, N., Ishizuka, K., et al. (2023) · Clinical and Experimental Medicine · doi:10.1007/s10238-023-01057-6 · Cited by 33
“The results of the present study mirror the results of the previous studies; because POTS is therapeutic [17], it is important to perform orthostatic testing in patients with long COVID who complain of fatigue.”
ResultTransdermal auricular vagus stimulation for the treatment of postural tachycardia syndrome
Diedrich, A., Urechie, V., Shiffer, D., Rigo, S., Minonzio, M., Cairo, B., Smith, E. C., Okamoto, L. E., Barbic, F., Bisoglio, A., et al. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102886 · Cited by 36
Defining Cardiac Dysautonomia – Different Types, Overlap Syndromes; Case-based Presentations
Lakkireddy, D. (2020) · Journal of Atrial Fibrillation · doi:10.4022/jafib.2403 · Cited by 33
Headache and Autonomic Dysfunction: a Review
Iser, C. R., & Arca, K. N. (2022) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-022-01225-3 · Cited by 26
“If examined within the context of hypovolemia, a known mechanism of POTS, the epidural venous hypotension theory may offer a connection between the disorders [69, 70].”
BackgroundMechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome
Tu, Y., Abell, T. L., Raj, S. R., & Mar, P. L. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.14031 · Cited by 27
Self-citationThe risks of POTS after COVID-19 vaccination and SARS-CoV-2 infection: more studies are needed
Blitshteyn, S., & Fedorowski, A. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00180-z · Cited by 24
A case of transient POTS following COVID-19 vaccine
Park, J., Kim, S., Lee, J., et al. (2022) · Acta Neurologica Belgica · doi:10.1007/s13760-022-02002-2 · Cited by 20
“However, POTS patients will sometimes manifest features from more than one of the three mechanisms, resulting in the clinical heterogeneity seen in this syndrome [5].”
BackgroundSnapper, H., & Cheshire, W. P. (2022) · Autonomic Neuroscience · doi:10.1016/j.autneu.2022.102951 · Cited by 17
Cerebral Blood Flow in Orthostatic Intolerance
Khan, M. S., Miller, A. J., Ejaz, A., Molinger, J., Goyal, P., MacLeod, D. B., SWAVELY, A. G., WILSON, E. R., Pergola, M., Tandri, H. S., et al. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.036752 · Cited by 22
“20 More specifically, in OI, venous pooling increases due to impairment of the skeletal muscle pump 21 and decreased splanchnic vasoconstriction.”
Self-citationZhang, Q., Xu, B., & Du, J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00525 · Cited by 20
Cai, H., Wang, S., Zou, R., Wang, Y., & Wang, C. (2020) · Autonomic Neuroscience · doi:10.1016/j.autneu.2020.102715 · Cited by 17
Tilt table testing, methodology and practical insights for the clinic
van Zanten, S., Sutton, R., Hamrefors, V., Fedorowski, A., & de Lange, F. J. (2023) · Clinical Physiology and Functional Imaging · doi:10.1111/cpf.12859 · Cited by 18
Sympathetic function and markers of inflammation in well-controlled HIV
Robinson‐Papp, J., Astha, V., Nmashie, A., Sharma, S. K., Kim‐Schulze, S., Murray, J., George, M. C., Morgello, S., Mueller, B. R., Lawrence, S., et al. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100112 · Cited by 16
Symptom presentation by phenotype of postural orthostatic tachycardia syndrome
Angeli, A. M., Salonen, B. R., Ganesh, R., Hurt, R. T., Abdalrhim, A. D., Mueller, M., Volcheck, M. M., & Aakre, C. A. (2024) · Scientific Reports · doi:10.1038/s41598-023-50886-8 · Cited by 20
“For hypovolemic POTS, interventions are aimed at increasing plasma volume, including but not limited to high fluid and salt intake, exercise, and fludrocortisone 3 .”
BackgroundInfluentialExperiences of living with postural tachycardia syndrome
Waterman, S., Opie, M., Waterman, D., & Langdon, D. W. (2021) · Chronic Illness · doi:10.1177/17423953211054032 · Cited by 17
“As the dysfunction relates to the autonomic nervous system, the condition generally has a multisystem impact.(7) Due to the diversity in presentation, as well as lack of clarity around the underlying mechanisms, diagnosis can be delayed by several years(8) and many patients are misdiagnosed as experiencing panic disor…”
BackgroundGhazal, M., Akkawi, A. R., Fancher, A. J., Oundo, E., Tanzeem, H., Sajjad, L., & Briasoulis, Α. (2024) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2024.102977 · Cited by 17
Cai, H., Wang, S., Zou, R., Li, F., Zhang, J., Wang, Y., Xu, Y., & Wang, C. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.644461 · Cited by 13
Management of orthostatic intolerance in children: the state of the art
Tao, C., Jin, H., & Du, J. (2020) · World Journal of Pediatrics · doi:10.1007/s12519-019-00329-0 · Cited by 11
Rodriguez, B., Hochstrasser, A., Eugster, P. J., Grouzmann, E., Müri, R., & Z'Graggen, W. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.968725 · Cited by 10
“Nevertheless, these findings indicate that patients with neuropathic POTS appear to experience some degree of hyperadrenergic state in the upright position under conditions similar to those in our study, as has been suggested by other research groups (Mar and Raj, 2020).”
ResultCai, H., Wang, S., Zou, R., Liu, P., Li, F., Wang, Y., & Wang, C. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.691390 · Cited by 11
Postural orthostatic tachycardia syndrome: pathophysiology, management, and experimental therapies
Narasimhan, B., Aggarwal, D., Satish, P., Kantharia, B. K., & Aronow, W. S. (2022) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2121697 · Cited by 12
“This dysautonomia can also lead to impaired sudomotor responses and acrocyanosis of distal extremities [8,13].”
BackgroundNon-invasive Vagus Nerve Simulation in Postural Orthostatic Tachycardia Syndrome
Chakraborty, P., Farhat, K., Morris, L. M., Whyte, S., Yu, X., & Stavrakis, S. (2023) · Arrhythmia & Electrophysiology Review · doi:10.15420/aer.2023.20 · Cited by 11
“46,47 HRV analysis showed reduced HF components along with increased LF and LF/HF ratio in the immunised animals compared with preimmune values.”
BackgroundSteinberg, R., Dicken, W., & Cutchins, A. C. (2023) · US Cardiology Review · doi:10.15420/usc.2022.35 · Cited by 11
“74 These medications may be beneficial and tolerated better in hyperadrenergic POTS than in neuropathic POTS.”
BackgroundRestless legs syndrome is increased in postural orthostatic tachycardia syndrome
Dodson, C., Bagai, K., Weinstock, L. B., Thompson, E., Okamoto, L. E., Peltier, A., Raj, S. R., & Walters, A. S. (2020) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.9020 · Cited by 9
Self-citationCirculating levels of growth hormone in postural orthostatic tachycardia syndrome
Johansson, M., Ricci, F., Schulte, J., Persson, M., Melander, O., Sutton, R., Hamrefors, V., & Fedorowski, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-87983-5 · Cited by 9
Guo, Y., Li, H., Deng, J., Zhang, G., Fischer, H., Stavrakis, S., & Yu, X. (2022) · Heart Rhythm O2 · doi:10.1016/j.hroo.2022.12.001 · Cited by 9
“There are no widely accepted treatment algorithms or consensus on the management strategy for different subtypes of POTS.(1,2) Pharmacologic treatment of hyperadrenergic POTS primarily focuses on suppressing sympathetic activity or increasing parasympathetic activity.”
BackgroundMethodInfluentialEvidence for Impaired Renin Activity in Postural Orthostatic Tachycardia Syndrome
Spahic, J. M., Mattisson, I. Y., Hamrefors, V., Johansson, M., Ricci, F., Nilsson, J. Å., Melander, O., Sutton, R., & Fedorowski, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12144660 · Cited by 8
“Patients with POTS fulfilled predefined diagnostic POTS criteria, including symptoms of orthostatic intolerance for at least 6 months and a positive head-up tilt test (HUT), confirming heart rate (HR) increase > 30 beats per minute (bpm), or HR exceeding 120 bpm when tilted from supine to upright position, according t…”
MethodPhysiological effects of ivabradine in heart failure and beyond
Iness, A. N., Shah, K., & Kukreja, R. C. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04862-5 · Cited by 8
Stick, M., Leone, A., Fischer, F., Schulz, J. B., & Maier, A. (2024) · European Journal of Neurology · doi:10.1111/ene.16402 · Cited by 7
“The resulting decreased venous return leads to reduced stroke volume, blood pressure (BP), and both thoracic and cerebral perfusion [ 4, 8, 9 ].”
BackgroundPostural Orthostatic Tachycardia Syndrome Associated with COVID-19: A Narrative Review
Park, J., Park, S., Kim, N.-H., Lee, Y., Chang, Y., & Song, T. (2024) · Medicina · doi:10.3390/medicina60081325 · Cited by 11
“Clonidine and methyldopa may be effective for POTS by decreasing central sympathetic signals [75].”
BackgroundG protein-coupled receptors related to autoimmunity in postural orthostatic tachycardia syndrome
Sunami, Y., Sugaya, K., & Takahashi, K. (2024) · Immunological Medicine · doi:10.1080/25785826.2024.2370079 · Cited by 6
“As non-pharmacological interventions, the clinicians can educate the patients about wearing compression stockings, the importance of adequate exercise and hydration (targeting 3 L of fluid intake per day), and a high-sodium diet (targeting 8–10 g of NaCl intake per day) [14].”
Distinct Hemodynamic Responses That Culminate With Postural Orthostatic Tachycardia Syndrome
de Oliveira, M. D. C. S., Távora‐Mehta, M. Z. P., Mehta, N., Magajevski, A. S., Concato, L., Ortiz, M. R., Doubrawa, E., & Lofrano‐Alves, M. S. (2023) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.03.027 · Cited by 7
MAGRO, C. M. J., Stephan, C., & Kalomeris, T. A. (2024) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2024.09.020 · Cited by 6
Postural tachycardia syndrome (POTS) and antiphospholipid syndrome (APS): What do we know so far?
Noureldine, H. A., Hasbani, G. E., Eldine, M. N., Nour‐Eldine, W., Taher, A. T., & Uthman, I. W. (2021) · Revue Neurologique · doi:10.1016/j.neurol.2021.10.006 · Cited by 6
Salt: The paradoxical philosopher's stone of autonomic medicine
Cheshire, W. P. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102895 · Cited by 6
Wheeler, C. M., Pacheco, J. M., Kim, A. C., Camacho-Santiago, M., Kalafut, M. A., AHERN, T. S., White, A. A., Patay, B. A., & Criado, J. R. (2022) · Applied Psychophysiology and Biofeedback · doi:10.1007/s10484-022-09536-4 · Cited by 6
“These studies provided additional support to the literature of elevated levels of psychological and autonomic symptoms in POTS patients (Mar & Raj, 2020).”
BackgroundResultInfluentialShiffer, D., Rigo, S., Minonzio, M., Yarsuvat, D. T., Tobaldini, E., Furlan, L., Montano, N., Cairo, B., Porta, A., Zamunér, A. R., et al. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.106529 · Cited by 8
Yeh, S.-J., Lung, C.-W., Jan, Y., Lee, L.-L., Wang, Y., & Liau, B.-Y. (2024) · Scientific Reports · doi:10.1038/s41598-024-77065-7 · Cited by 5
Wang, Z., Zhu, T., Li, X., Lai, X., & Chen, M. (2025) · Clinical Cardiology · doi:10.1002/clc.70110 · Cited by 6
“Despite the availability of conventional pharmacological and non-pharmacological therapies, the current treatment options for POTS are limited by their efficacy and the prevalence of cardiac and noncardiac side effects [5, 6].”
Hereditary alpha-tryptasemia in patients with postural orthostatic tachycardia syndrome
Huang, J., Imam, K. H., Criado, J. R., Luskin, K. T., Liu, Y., Puglisi, L. H., Lyons, J. J., & White, A. A. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.10.043 · Cited by 5
Wang, S., Zou, R., Cai, H., & Wang, C. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.802469 · Cited by 5
Fan, S., Cui, Y., Liao, Y., & Jin, H. (2023) · Children · doi:10.3390/children10071093 · Cited by 7
Malkova, A. M., & Shoenfeld, Y. (2022) · Autoimmunity Reviews · doi:10.1016/j.autrev.2022.103231 · Cited by 5
RetractedPostural orthostatic tachycardia syndrome explained using a baroreflex response model
Geddes, J. R., Ottesen, J. T., Mehlsen, J., & Olufsen, M. S. (2022) · Journal of The Royal Society Interface · doi:10.1098/rsif.2022.0220 · Cited by 5
Postural Tachycardia Syndrome and COVID-19: Focus on Ivabradine Therapy
DIXIT, K., & Frishman, W. H. (2022) · Cardiology in Review · doi:10.1097/crd.0000000000000503 · Cited by 4
Saunders, D., Arnold, T. B., Lavender, J. M., Bi, D., Alcover, K. C., Hellwig, L. D., Leazer, S. T., Mohammed, R., Markos, B., Perera, K. U., et al. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1550636 · Cited by 6
Perioperative and anesthetic considerations for post-acute sequelae of COVID (PASC)/long COVID
Yogendra, R., Perlowski, A., Johng, B., Dahshan, H. H., Orr, C., Jeffers, D., Husain, K., & Patterson, B. K. (2025) · Perioperative Medicine · doi:10.1186/s13741-025-00558-0 · Cited by 4
Song, J., Tao, C., Chen, G., Chen, S. Y., Xu, W., Du, J., Yang, Y., & Huang, Y. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.00098 · Cited by 3
Postural Orthostatic Tachycardia Syndrome: Diagnosis and Management Guide for Nurses
Seeley, M., Lau, D. H., & Gallagher, C. (2023) · Nursing Research and Reviews · doi:10.2147/nrr.s394822 · Cited by 3
“39 However, clinically it can be challenging to differentiate subtypes due to frequent overlap in clinical presentations, and difficulty in undertaking the clinical tests required for categorisation.”
BackgroundSymptomatic use of carbidopa in autonomic disorders
Golden, E. P., Park, C. J., & Vernino, S. A. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102888 · Cited by 3
Pagel, P. S., Hang, D., Freed, J. K., & Crystal, G. J. (2025) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2025.03.029 · Cited by 3
Pei, Z., Hui, Z. Y., Yang, L., Liang, Z., & Min, Z. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1642869 · Cited by 2
“Potential causes include a partially denervated circulatory system, a hyperadrenergic state, hypovolemia, peripheral blood pooling, or prolonged bed rest (15).”
Tran, H. H.-V., Thu, A., Fuertes, A., Twayan, A. R., Mehta, K. A., Basta, M., Mahadevaiah, A., Islek, D., Weissman, S. I., Frishman, W. H., et al. (2025) · Cardiology in Review · doi:10.1097/crd.0000000000000953 · Cited by 2
Saunders, D., Arnold, T. B., Lavender, J. M., Bi, D., Alcover, K., Hellwig, L., Leazer, S. T., Mohammed, R., Markos, B., Perera, K. U., et al. (2023) · medRxiv · doi:10.1101/2023.04.25.23289110 · Cited by 4
“The Postural Orthostatic Tachycardia Syndrome (POTS) sometimes referred to as Soldier’s Heart or DaCosta’s Syndrome is a particularly debilitating condition (2).”
BackgroundRodriguez, B., Pantano, L., Nef, T., Müri, R. M., & Z'Graggen, W. J. (2024) · European Journal of Neurology · doi:10.1111/ene.16507 · Cited by 2
Interdisciplinary Rehabilitation Approaches in Functional Movement Disorder
LaFaver, K., & Ricciardi, L. (2022) · Current clinical neurology · doi:10.1007/978-3-030-86495-8_26 · Cited by 3
Harbeck‐Weber, C., Klaas, K. M., Sim, L. A., Weiss, K., Shappell, A., & Harrison, T. E. (2025) · Children · doi:10.3390/children12020186 · Cited by 2
“Proposed mechanisms include partial autonomic neuropathy, persistent tendency toward hypovolemia, and central hyperadrenergic state, with many patients having multiple pathophysiologic contributors [26].”
Prolonged, Recurrent, and Periodic Fever Syndromes
Manthiram, K., Edwards, K. M., & Long, S. S. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-75608-2.00015-x · Cited by 2
Ljungström, M., Oltra, E., & Pardo, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147778 · Cited by 2
“Some CFS cases and individuals with postural orthostatic tachycardia syndrome (POTS) often present with a hyperadrenergic state [16,17].”
BackgroundUsing Clonidine for neuromodulation in patients with postural orthostatic tachycardia syndrome
Lin, S., Kote, A., Andersson, T., Goldhaber, J. I., Tisdale, J. E., Li, X., Chen, P., & Liu, X. (2025) · Heart Rhythm · doi:10.1016/j.hrthm.2025.05.003 · Cited by 2
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The influence of sex on the treatment of postural tachycardia syndrome in children
Peng, Y., Wang, S., Zou, R., Cai, H., Zhang, J., Wang, Y., & Wang, C. (2023) · Medicine · doi:10.1097/md.0000000000033951 · Cited by 4
Pierson, B. C., Craig-Kuhn, M. C., Stewart, L. M., Sercy, E., Stern, C. A., Graham, B., Michel, A., Parmelee, E., Koehlmoos, T. P., Saunders, D., et al. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1653175 · Cited by 1
“This finding is interesting given that these medications are routinely used in the management of dysautonomia conditions (46).”
Toma, M., Jose, R., Syed, F., & Devine, T. J. (2024) · Clinics and Practice · doi:10.3390/clinpract14050138 · Cited by 1
“The management of OH involves a combination of pharmacological and non-pharmacological strategies [3,4].”
BackgroundManagement of Postural Orthostatic Tachycardia Syndrome: A Canadian Approach
Hussein, M. T. E., & Hewko, A. (2024) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2024.105258 · Cited by 1
Recognizing postural orthostatic tachycardia syndrome in primary care
Hulsey, B. (2023) · JAAPA · doi:10.1097/01.jaa.0000991396.00397.be · Cited by 1
Malik, V., Roy, B., Sarkar, A. E. H., Shivkumar, K., Khalsa, S. S., Kumar, R., & Ajijola, O. A. (2026) · Heart Rhythm · doi:10.1016/j.hrthm.2026.02.020 · Cited by 2
Effect of Comorbid Dysautonomia on Postoperative Complications in Sinonasal Surgery
Dawood, E., Saeedi, A., & Schuman, T. A. (2026) · American Journal of Rhinology and Allergy · doi:10.1177/19458924251413870 · Cited by 1
Figueroa, A. V., Cifuentes, S., Ulloa, J. H., & Raffetto, J. D. (2024) · Journal of Vascular Surgery Cases and Innovative Techniques · doi:10.1016/j.jvscit.2024.101483 · Cited by 1
“16,17 Knuttinen et al reported an association be-tween left CIV stenosis and POTS, 18 with some patients with POTS demonstrating improvement in his symptoms after vein stenting.”
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Novel pharmacotherapeutic options for the treatment of postural orthostatic tachycardia syndrome
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“Although treatment with IVIG was not well tolerated by many participants, it is believed that adequate pretreatment with steroids and hydration will improve tolerance [27].”
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Troubles fonctionnels cardiorespiratoires : une approche transnosologique
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Sinus Tachycardias: Inappropriate Sinus Tachycardia and Postural Orthostatic Tachycardia Syndrome
Talati, A., Uppal, J., Sheldon, R. S., & Raj, S. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15734-9.00016-9
Self-citationExercise for Postural Orthostatic Tachycardia Syndrome: Challenges and Opportunities to Improve
Rasnake, E. B., Kouvel, K., Cooper, S., & Greenberg, E. M. (2025) · Cardiopulmonary Physical Therapy Journal · doi:10.1097/cpt.0000000000000304 · Cited by 1
The endometriosis-POTS connection: A retrospective analysis
Chin, A. Y., Rilinger, R. G., Levine, M. A., Nowacki, A. S., Brant, A. R., Cameron, C., Gubbels, A. L., & Wilson, R. (2026) · Autonomic Neuroscience · doi:10.1016/j.autneu.2026.103469 · Cited by 1
Syncope and Postural Orthostatic Tachycardia Syndrome
Moodley, M. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-10944-7.00108-6
Cao, Y., Liu, P., Li, B., Zhang, Y., Du, J., Jin, H., & Liao, Y. (2025) · Children · doi:10.3390/children12040474
“In addition, many patients with POTS also have a primary hyperadrenergic state, and the sympathetic tone is markedly increased, and even more when standing [40,41], which can cause a marked increase in heart rate [42], and as a result, their discomfort is more pronounced when they are upright.”
Евлахов, В. И., Berezina, T. P., Sergeev, T. V., et al. (2024) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093024030050
“In the latter case, the nonselec(cid:2) tive β 1,2 -adrenoreceptor blocker propranolol, β 1 - blocker bisoprolol, and central agonist of inhibitory presynaptic α 2 -adrenoreceptor methyldopa are applied to correction the above syndrome pharma(cid:2) cologically [4].”
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[Research progress in the application of ivabradine in children with cardiovascular diseases].
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Treatment of Headache in Children and Adolescents with POTS
Nayak, K., Rahman, S., & Oakley, C. B. (2026) · Current Pain and Headache Reports · doi:10.1007/s11916-026-01516-1
何, 川. (2025) · Advances in Clinical Medicine · doi:10.12677/acm.2025.1541208
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Kwok, C. S., Lee, S., Afzal, A., Choi, L., Nazari, B., Hall, M., Loke, Y. K., Qureshi, A. I., & Raj, S. R. (2026) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001822
Self-citationGut hormones in POTS and their relation to hemodynamic parameters and gastrointestinal symptoms
Tufvesson, H., Roth, B., Johansson, M., Hamrefors, V., Fedorowski, A., Lindholm, E., & Ohlsson, B. (2026) · Scientific Reports · doi:10.1038/s41598-026-52963-0 · Cited by 1
Late-onset sequelae after right middle and lower lobectomy: a case report
Li, S., Chen, W., Zha, J., Xu, Z., Lee, V. H.-F., & Lee, A. W. M. (2026) · Journal of Medical Case Reports · doi:10.1186/s13256-026-06056-1
Feeling shaky with palpitations
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Metadata
- Authors
- Mar, P. L., & Raj, S. R.
- Affiliations
- Saint Louis University (US)
- University of Calgary (CA)
- Venue
- Annual Review of Medicine
- Publisher
- Annual Reviews
- Published
- 2020-01-27
- Volume
- 71
- Issue
- 1
- Pages
- 235-248
- ISSN
- 0066-4219 (ISSN-L)
- 1545-326X
- OpenAlex
- W2967501582
- Semantic Scholar
- 392e517d5ad05ac895e6046186443346358a7d07
- Cited by
- 122
- References
- 85
- Citations by year
- 2026: 21 · 2025: 21 · 2024: 23 · 2023: 16 · 2022: 18 · 2021: 13 · 2020: 10
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000445)
- Canadian Institutes of Health Research (42426_1)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Keywords
- postural orthostatic tachycardia syndrome, orthostatic intolerance, autonomic neuropathy, hypovolemia, hyperadrenergic state, pathophysiology, compression garments, abdominal binder, vasoconstrictors, exercise therapy, volume expansion, beta-blockers, norepinephrine reuptake inhibitors, personalized treatment
- MeSH terms
- Ivabradine, Adrenergic beta-Antagonists, Cardiovascular Agents, Clonidine, Combined Modality Therapy, Female, Humans, Male, Methyldopa, Quality of Life, Severity of Illness Index, Survival Analysis, Treatment Outcome, Risk Assessment, Postural Orthostatic Tachycardia Syndrome
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