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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
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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.
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- Findingnone given§ Abstract
Patients with POTS often exhibit overlapping characteristics from more than one of the three major pathophysiologic mechanisms.
“Patients often will exhibit overlapping characteristics from more than one of these mechanisms.”
Quote in the paperSubstantial claim - Premisecitation§ Neuropathic POTS (Partial Autonomic Neuropathy)
POTS patients have significantly impaired sympathetic nervous system activity in the lower extremities.
“Jacob et al. (18) demonstrated significantly impaired sympathetic nervous system activity in the lower extremities of POTS patients.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
- Premisecitation§ Neuropathic POTS (Partial Autonomic Neuropathy)
Norepinephrine release in the upper extremities in response to the same stimuli was no different between POTS patients and healthy controls.
“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.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
- Interpretationnone given§ Abstract
The three major pathophysiologic mechanisms of POTS are partial autonomic neuropathy, hypovolemia, and hyperadrenergic state.
“The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state.”
Quote in the paperNot a substantial claim - Premisecitation§ Neuropathic POTS (Partial Autonomic Neuropathy)
Pediatric patients with POTS had excessive pooling of blood in the lower extremities, primarily due to arteriolar dysregulation rather than inappropriately increased venous capacitance.
“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.”
Quote in the paperNot a substantial claim0 of 4 sources checked
- Premisecitation§ Neuropathic POTS (Partial Autonomic Neuropathy)
Norepinephrine release at sympathetic nervous system synapses in the lower extremities in response to cold pressor test, nitroprusside infusion, and tyramine infusion was markedly lower in POTS patients than in healthy controls.
“Amounts of norepinephrine released at sympathetic nervous system synapses in the lower extremities in response to a cold pressor test, a nitroprusside infusion, and a tyramine infusion were markedly lower in POTS patients than in healthy controls.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
- Premisecitation§ Figure 1
Partial autonomic neuropathy in POTS extends beyond the lower extremities into the pelvic and splanchnic circulation.
“The extent of partial autonomic neuropathy extends beyond the lower extremities into the pelvic and splanchnic circulation.”
Quote in the paperSubstantial claim0 of 5 sources checked - Premisecitation§ Figure 1
Doppler ultrasound and plethysmography studies have demonstrated abnormally increased blood flow and pooling in the splanchnic and pelvic circulation of POTS patients both at rest and in an upright position.
“Both Doppler ultrasound and plethysmography studies have demonstrated abnormally increased blood flow and pooling in the splanchnic and pelvic circulation of POTS patients both at rest and in an upright position (20-24).”
Quote in the paperSubstantial claim0 of 5 sources checked - Premisecitation§ PATHOPHYSIOLOGY
Many conditions such as mast cell activation disorders, Ehlers-Danlos syndrome, deconditioning, and genetic mutations of norepinephrine transporters coexist with POTS, and their downstream effects funnel into the three principal pathophysiologic mechanisms.
“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.”
Quote in the paperSubstantial claim0 of 4 sources checked - Premisecitation§ PATHOPHYSIOLOGY
The literature has identified three different pathophysiologic mechanisms capable of manifesting the POTS phenotype: partial autonomic neuropathy, persistent predilection for hypovolemia, and central hyperadrenergic state.
“Thus far, the literature has identified three different pathophysiologic mechanisms that are capable of manifesting the POTS phenotype: ( a ) partial autonomic neuropathy, ( b ) persistent predilection for hypovolemia, and ( c ) central hyperadrenergic state.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] source
- Interpretationcitation§ PATHOPHYSIOLOGY
The three pathophysiologic mechanisms engender somewhat distinct variants of the POTS phenotype, referred to as endophenotypes.
“These three pathophysiologic mechanisms engender somewhat distinct variants of the POTS phenotype that henceforward will be referred to as endophenotypes (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] source
- Premisecitation§ Hypovolemic POTS
Plasma angiotensin 2 levels in some POTS patients are elevated on the order of 2-3 times higher than healthy controls.
“Further investigations into the renin-angiotensin aldosterone system (RAAS) revealed that plasma angiotensin 2 (Ang-II) levels in some POTS patients are elevated (on the order of 2-3 times higher) when compared to healthy controls (35, 36).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Figure 1
Neuronal nitric oxide synthase, and not endothelial nitric oxide synthase, was determined to be responsible for causing this phenomenon.
“Neuronal nitrous oxide synthase, and not endothelial nitrous oxide synthase, was determined to be responsible for causing this phenomenon (29).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] source
- Premisecitation§ Figure 1
Evidence of autoantibodies that act as partial alpha-1 antagonists has been found in POTS patients.
“Evidence of autoantibodies that act as partial alpha-1 antagonists have also been found in POTS patients (32).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] source
- Premisecitation§ Hypovolemic POTS
Despite low blood and plasma volumes, plasma renin activity and aldosterone levels are inappropriately low in POTS patients.
“Despite these low blood and plasma volumes, plasma renin activity and aldosterone levels are also inappropriately low in POTS patients.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Hypovolemic POTS
Despite high Ang-II levels, POTS patients are paradoxically prone to hypovolemia.
“Despite their high Ang-II levels, POTS patients are paradoxically prone to hypovolemia (37).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] source
- Premisecitation§ Hypovolemic POTS
Some POTS patients have 13-22% less plasma or blood volume than healthy controls.
“Studies have shown that some POTS patients have 13-22% less plasma or blood volume than do healthy controls (33-35).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation§ Figure 1
POTS patients have significantly greater decreases in thoracic and cerebral blood flow when compared to healthy controls during tilt.
“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).”
Quote in the paperSubstantial claim0 of 5 sources checked - Premisecitation§ Hypovolemic POTS
A significant portion of POTS patients suffer from a state of persistent hypovolemia.
“A significant portion of POTS patients suffer from a state of persistent hypovolemia.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation§ Hypovolemic POTS
The decrease in stroke volume was out of proportion to the degree of plasma volume reduction, as predicted by the Starling curve.
“The decrease in stroke volume, as predicted by the Starling curve, was out of proportion to the degree of plasma volume reduction (41).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] source
- Premisecitation§ Hypovolemic POTS
POTS patients have an attenuated hypertensive response to Ang-II versus healthy control subjects after infusion of a standardized dose of Ang-II.
“This is supported by the finding that POTSpatients have an attenuated hypertensive response to Ang-II versus healthy control subjects after infusion of a standardized dose of Ang-II (38).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] source
- Premisecitation§ Figure 1
Medow et al. found defective cutaneous vasodilation of the microvasculature mediated by nitric oxide with local heating in POTS patients versus healthy control subjects.
“Medow et al. (28) found defective cutaneous vasodilation of the microvasculature mediated by nitric oxide with local heating in POTS patients versus healthy control subjects.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] source
- Interpretationreasoning§ Hypovolemic POTS
Deconditioning, with its subsequent plasma volume reduction and decreased stroke volume, may play a significant role in the development of a POTS phenotype.
“This finding suggests that deconditioning, with its subsequent plasma volume reduction and decreased stroke volume, may play a significant role in the development of a POTS phenotype (42).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42] source
- Premisecitation§ Figure 1
A significant proportion of patients with Ehlers-Danlos syndrome exhibit autonomic dysfunction and orthostatic intolerance.
“A significant proportion of patients with Ehlers-Danlos syndrome exhibit autonomic dysfunction and orthostatic intolerance (11).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] source
- Premisecitation§ Figure 1
De Wandele et al. performed autonomic function testing in 39 patients with Ehlers-Danlos syndrome and found that orthostatic intolerance was much more common in this population.
“De Wandele et al. (30) performed autonomic function testing in 39 patients with Ehlers-Danlos syndrome and found that orthostatic intolerance was much more common in this population.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] source
- Premisecitation§ Hypovolemic POTS
In six previously healthy male astronauts, just 16 days of spaceflight resulted in a decrease in blood volume of nearly 6%.
“Levine et al. (39) demonstrated that in six previously healthy male astronauts, just 16 days of spaceflight resulted in a decrease in blood volume of nearly 6% (39).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [39] source
- Interpretationcitation§ Figure 1
These autoantibodies could have an effect similar to a partial autonomic neuropathy due to inadequate vasoconstriction in response to alpha-adrenergic stimulation.
“These could have an effect similar to a partial autonomic neuropathy due to inadequate vasoconstriction in response to alpha-adrenergic stimulation ( Figure 1 ).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] source
- Premisecitation§ Hypovolemic POTS
The aldosterone:renin ratio is lower in POTS patients than in healthy control subjects.
“Additionally, the aldosterone:renin ratio was found to be lower in POTS patients than in healthy control subjects (34).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] source
- Premisecitation§ Figure 1
Mast cell activation disorders frequently coexist with POTS.
“Mast cell activation disorders are another condition that frequently coexists with POTS (9).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] source
- Premisecitation§ Treatment for Partial Autonomic Neuropathy
Graded compression garments and abdominal binders have improved symptoms of orthostatic intolerance in conditions associated with excessive blood pooling.
“Graded compression garments and abdominal binders have improved symptoms of orthostatic intolerance in conditions associated with excessive blood pooling (52, 53).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Hyperadrenergic POTS
One of the twins became hypertensive with standing.
“One of the twins even became hypertensive with standing (13).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] source
- Premisecitation§ Hyperadrenergic POTS
Hyperadrenergic POTS is an important endophenotype of POTS with the characteristic neurohormonal hallmark of elevated upright plasma norepinephrine.
“Hyperadrenergic POTS is an important endophenotype of POTS with the characteristic, neurohormonal hallmark of elevated upright plasma norepinephrine (34, 36).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Hyperadrenergic POTS
Administration of reboxetine, a norepinephrine transporter inhibitor, to healthy controls provoked hemodynamic changes consistent with POTS.
“Administration of reboxetine, a norepinephrine transporter inhibitor, to healthy controls provoked hemodynamic changes consistent with POTS (48).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [48] source
- Premisecitation§ Hyperadrenergic POTS
Supine levels of norepinephrine are similar between healthy controls and POTS patients.
“Supine levels of norepinephrine are similar between healthy controls and POTS patients (34).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] source
- Premisecitation§ Hyperadrenergic POTS
Higher levels of autoantibodies against beta-1 and beta-2 adrenoreceptors have been detected in POTS patients versus healthy controls in serologic studies.
“Higher levels of autoantibodies against beta-1 and beta-2 adrenoreceptors have been detected in POTS patients versus healthy controls in serologic studies (32, 44).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning§ Overlapping Pathophysiology and Clinical Heterogeneity
This overlap is likely due to the contribution of multiple pathophysiologic mechanisms to their unique phenotype, resulting in the clinical heterogeneity seen in this syndrome.
“This is likely due to the contribution of multiple pathophysiologic mechanisms to their unique phenotype, resulting in the clinical heterogeneity seen in this syndrome.”
Quote in the paperSubstantial claim - Premisecitation§ Treatment for Partial Autonomic Neuropathy
Octreotide, a subcutaneously injectable somatostatin analog, causes vasoconstriction in the splanchnic vascular bed.
“Octreotide, a subcutaneously injectable somatostatin analog that causes vasoconstriction in the splanchnic vascular bed, has also been studied in POTS patients (59).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [59] source
- Premisecitation§ Treatment for Partial Autonomic Neuropathy
In a study of patients with autonomic failure, abdominal compression of 40 mmHg was as effective as midodrine.
“In a study of patients with autonomic failure, abdominal compression of 40 mmHg was as effective as midodrine (53).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [53] source
- Premisecitation§ Treatment for Partial Autonomic Neuropathy
Administration of 5-10 mg doses of midodrine acutely reduced both supine and upright heart rate (from 108 bpm to 95 bpm) in 13 patients with POTS.
“Administration of 5-10 mg doses acutely reduced both supine and upright heart rate (from 108 bpm to 95 bpm) in 13 patients with POTS.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [54] source
- Premisecitation§ Hyperadrenergic POTS
Autoantibody affinity toward beta-receptors positively correlated with a greater degree of orthostatic tachycardia.
“This group also demonstrated that autoantibody affinity toward beta-receptors positively correlated with a greater degree of orthostatic tachycardia (44).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] source
- Premisecitation§ Treatment for Partial Autonomic Neuropathy
The combination of abdominal binders and lower extremity compression stockings is thought to be more effective than lower extremity compression alone due to the disproportionally greater volume in the splanchnic circulation than in the legs.
“The combination of abdominal binders and lower extremity compression stockings is thought to be more effective than lower extremity compression alone due to the disproportionally greater volume in the splanchnic circulation than in the legs (51).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [51] source
- Premisecitation§ Hyperadrenergic POTS
Alteration of norepinephrine metabolism, congenital or iatrogenic, is another well-described cause of hyperadrenergic POTS.
“Alteration of norepinephrine metabolism, congenital or iatrogenic, is another well-described cause of hyperadrenergic POTS.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] source
- Interpretationcitation§ Overlapping Pathophysiology and Clinical Heterogeneity
POTS may simply be a final common pathway for several interrelated pathophysiologic mechanisms.
“POTS may simply be a final common pathway for several interrelated pathophysiologic mechanisms (50).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [50] source
- Premisecitation§ Overlapping Pathophysiology and Clinical Heterogeneity
POTS patients will sometimes manifest features from more than one of the three major POTS endophenotypes.
“POTS patients will sometimes manifest features from more than one of the three major POTS endophenotypes (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] source
- Premisecitation§ Hyperadrenergic POTS
The binding of these autoantibodies to the adrenergic receptors is postulated to drive the tachycardia in some POTS patients.
“The binding of these autoantibodies to the adrenergic receptors is postulated to drive the tachycardia in some POTS patients (32).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] source
- Interpretationreasoning§ Hyperadrenergic POTS
In hyperadrenergic POTS, the predominant symptom is palpitations due to orthostatic tachycardia that is primarily driven by a hyperadrenergic state.
“In this endophenotype, the predominant symptom is palpitations due to orthostatic tachycardia that is primarily driven by a hyperadrenergic state.”
Quote in the paperNot a substantial claim - Premisecitation§ Treatment for Partial Autonomic Neuropathy
Midodrine has been shown to be more effective in treating neuropathic POTS than hyperadrenergic POTS.
“Not surprisingly, midodrine has been shown to be more effective in treating neuropathic POTS than hyperadrenergic POTS (56).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [56] source
- Premisecitation§ Hyperadrenergic POTS
Levels of plasma epinephrine appear to be similar between POTS patients and healthy subjects.
“Levels of plasma epinephrine appear to be similar between POTS patients and healthy subjects (34, 36).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Hyperadrenergic POTS
Another study demonstrated that epigenetic modification of the SCL6A2 gene resulting in its downregulation was more prevalent in POTS patients than in healthy controls.
“Another study demonstrated that epigenetic modification of the SCL6A2 gene resulting in its downregulation was more prevalent in POTS patients than in healthy controls (45).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] source
- Interpretationreasoning§ Overlapping Pathophysiology and Clinical Heterogeneity
An all-unifying pathophysiologic mechanism does not exist.
“An all-unifying pathophysiologic mechanism does not exist.”
Quote in the paperSubstantial claim - Interpretationcitation§ CONCLUSION
In certain cases, it may be possible to recognize key endophenotypes in POTS.
“In certain cases, it may be possible to recognize key endophenotypes (13, 73, 79).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation§ Treatment for Hypovolemic POTS
Erythropoietin does not appear to improve the orthostatic tachycardia of POTS.
“Erythropoietin does not appear to improve the orthostatic tachycardia of POTS (71, 72)”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationnone given§ Treatment for Hyperadrenergic POTS
Modafinil can sometimes help with fatigue in POTS patients.
“Modafinil, an agent that is used to treat narcolepsy and promote wakefulness, can sometimes help with fatigue in POTS patients.”
Quote in the paperNot a substantial claim - Premisecitation§ Treatment for Hypovolemic POTS
50-70% of POTS patients who complete 3 months of endurance training exhibit hemodynamic changes that no longer meet criteria for POTS.
“In fact, 50-70% of POTS patients who complete 3 months of endurance training exhibit hemodynamic changes that no longer meet criteria for POTS (42, 62, 63).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation§ Treatment for Hyperadrenergic POTS
Pyridostigmine improves orthostatic tachycardia in POTS patients.
“pyridostigmine has been shown to improve orthostatic tachycardia in POTS patients.”
Quote in the paperSubstantial claim - Premisecitation§ CONCLUSION
Patients with POTS often report significant delays in diagnosis, exceeding five years between onset of symptoms and eventual diagnosis in many cases.
“Patients often report significant delays in diagnosis, exceeding five years between the onset of symptoms and eventual diagnosis in many cases.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
- Interpretationnone given§ Treatment for Hyperadrenergic POTS
Central-acting sympatholytic agents such as clonidine and methyldopa likely work by decreasing central sympathetic nerve traffic.
“Central-acting sympatholytic agents, such as clonidine and methyldopa, have also been used in POTS patients and likely work by decreasing central sympathetic nerve traffic.”
Quote in the paperNot a substantial claim - Premisecitation§ Treatment for Hypovolemic POTS
Short-term administration of oral DDAVP and water to POTS patients resulted in standing heart rates significantly lower than after placebo administration.
“The short-term administration of oral DDAVP and water to POTS patients resulted in standing heart rates significantly lower than that after placebo administration (69).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [69] source
- Premisecitation§ Treatment for Hypovolemic POTS
Acute infusions of normal saline afford rapid relief in patients with POTS crisis.
“Acute infusions of normal saline have been shown to afford rapid relief in patients with POTS crisis (8, 54)”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Treatment for Hypovolemic POTS
Higher plasma copeptin levels positively correlate with treatment response to midodrine in POTS patients.
“Higher levels of plasma copeptin, a peptide fragment of arginine vasopressin, which is a neurohormonal marker for relative hypovolemia, have been shown to positively correlate with treatment response to midodrine in POTS patients (73).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [73] source
- Premisecitation§ Treatment for Hypovolemic POTS
In POTS patients, six consecutive days of a low-sodium diet (10 mEq/day) resulted in significantly greater orthostatic tachycardia than six consecutive days of a high-sodium diet (300 mEq/day).
“One small prospective study demonstrated that, in POTS patients, six consecutive days of a low-sodium diet (10 mEq/day) resulted in significantly greater orthostatic tachycardia than six consecutive days of a high-sodium diet (300 mEq/day), highlighting the importance of sodium intake (66).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [66] Raj S, 2014, Heart Rhythm
- Premisecitation§ Treatment for Hypovolemic POTS
Fludrocortisone is considered the mainstay pharmacologic agent for volume expansion in patients with orthostatic intolerance and hypotension.
“Fludrocortisone, a synthetic aldosterone analog that causes sodium retention, is considered the mainstay pharmacologic agent for volume expansion in patients with orthostatic intolerance and hypotension (68).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [68] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
Small case series have shown that ivabradine reduces upright heart rate and improves symptoms associated with orthostatic intolerance.
“Small case series have shown that ivabradine reduces upright heart rate and improves symptoms associated with orthostatic intolerance (83, 84).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Treatment for Hyperadrenergic POTS
Studies suggest the true prevalence of psychiatric disorders in POTS patients may be no different than in the general population.
“especially in light of studies that suggest the true prevalence of psychiatric disorders in this patient population may be no different than in the general population (75).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [75] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
Further studies have demonstrated long-term benefits with using pyridostigmine in POTS patients.
“Further studies have also demonstrated long-term benefits with using pyridostigmine in POTS patients (81, 82).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationcitation§ Treatment for Hyperadrenergic POTS
Antidepressant use is likely high in POTS patients, given the high incidence of polypharmacy and the perception of increased depression in this population.
“Given the high incidence of polypharmacy in POTS patients (10), coupled with the perception of increased depression in POTS patients (74), antidepressant use is likely high in this patient population.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Treatment for Hyperadrenergic POTS
A small prospective study of POTS patients who failed beta-blockers demonstrated reductions in upright norepinephrine levels and increased plasma volume by 12% on doses of clonidine 0.3-0.4 mg/day.
“a small prospective study of patients who failed beta-blockers demonstrated reductions in upright norepinephrine levels and increased plasma volume by 12% on doses of clonidine 0.3-0.4 mg/day (86).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [86] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
Long-acting, once-daily propranolol did not improve quality of life at one month in POTS patients.
“In contrast, Fu et al. (64) showed that the long-acting, once-daily formulation of propranolol did not improve quality of life at one month.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [64] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
In the same study, supine and upright blood pressures were no different between the pyridostigmine group and the placebo group.
“Supine and upright blood pressures were no different between the group that received pyridostigmine and the placebo group.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [80] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
POTS patients with low copeptin levels were far more likely to respond to metoprolol than those with high copeptin levels.
“Zhao et al. (79) demonstrated that POTS patients with low copeptin levels were far more likely to respond to metoprolol than those with high levels of copeptin, presumably due to a greater contribution of the hyperadrenergic endophenotype to their syndrome.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [79] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
A large randomized prospective study demonstrated that propranolol, bisoprolol, propranolol + pyridostigmine, and bisoprolol + pyridostigmine all resulted in improvements in the Orthostatic Intolerance questionnaire, the Beck depression inventory, and the physical component of the SF-36.
“A large randomized prospective study demonstrated that propranolol, bisoprolol, propranolol + pyridostigmine, and bisoprolol + pyridostigmine all resulted in improvements in the Orthostatic Intolerance questionnaire, the Beck depression inventory, and the physical component of the SF-36 (77).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [77] source
- Premisecitation§ Treatment for Hypovolemic POTS
Only 41% of POTS patients in the community setting are able to complete a standardized 3-month program involving mild-moderate intensity endurance training 3-5 times per week at 30-45 min per session.
“Unfortunately, only 41% of POTS patients in the community setting are able to complete a standardized 3-month program involving mild-moderate intensity endurance training 3-5 times per week at 30-45 min per session (63).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [63] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
The main limitation of pyridostigmine's use is adverse gastrointestinal effects, which can include diarrhea, cramping, nausea, vomiting, and flatulence.
“The main limitation of pyridostigmine's use is adverse gastrointestinal effects, which can include diarrhea, cramping, nausea, vomiting, and flatulence (70).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [70] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
In a study of 17 POTS patients, symptoms and standing heart rate were significantly reduced after pyridostigmine administration versus placebo in the acute setting.
“In a study of 17 POTS patients, symptoms and standing heart rate were significantly reduced after pyridostigmine administration versus placebo in the acute setting (80).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [80] source
- Interpretationcitation§ Treatment for Hypovolemic POTS
Acute infusions of normal saline are not sustainable in the long term due to the potential for vascular access complications.
“but this approach is not sustainable in the long-term due to the potential for vascular access complications (67).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [67] source
- Premisecitation§ Treatment for Hyperadrenergic POTS
Modafinil 100 mg did not significantly increase acute supine or upright heart rate in POTS patients compared to placebo.
“Kpaeyeh et al. (87) demonstrated that modafinil 100 mg did not significantly increase the acute supine or upright heart rate in POTS patients compared to placebo.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [87] source
- Premisenone given§ Treatment for Hyperadrenergic POTS
The mainstay of sympathetic nervous system suppression is beta-blockers.
“The mainstay of sympathetic nervous system suppression is beta-blockers.”
Quote in the paperSubstantial claim
- It may state two separate claims as one. 30
- Probably not a substantial claim. 4
It may state two separate claims as one.
Interpretationnone given§ AbstractPOTS is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms.
“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.”
Quote in the paperSubstantial claimProbably not a substantial claim. It may be too vague to check against evidence.
Interpretationnone given§ PATHOPHYSIOLOGYPOTS should not be considered a disease but a clinical syndrome or phenotype.
“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.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Premisecitation§ Figure 1Mast cell degranulation causes release of vasoactive substances (histamine, prostaglandins, platelet-activating factor) into the circulation, potentially causing excessive vasodilation and blood pooling in the lower extremities.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] source
It may state two separate claims as one.
Premisecitation§ Figure 1Cutaneous 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.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] source
It may state two separate claims as one.
Premisecitation§ Hypovolemic POTSUnder normal gravitational conditions, two weeks of strict bedrest resulted in a 17% reduction in plasma volume and a near 10% reduction in stroke volume.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] source
It may state two separate claims as one.
Premisecitation§ Figure 1In Ehlers-Danlos syndrome, orthostatic intolerance primarily manifests as excessive orthostatic tachycardia and reduced QSART responses when compared to healthy controls.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] source
It may state two separate claims as one.
Premisecitation§ Hypovolemic POTSIn 18 cosmonauts who had spent several months on a space station, previously healthy individuals experienced moderate hemodynamic changes that almost meet some POTS criteria (average orthostatic heart rate increase by 26 bpm in absence of orthostatic hypotension), with one individual meeting the orthostatic tachycardia criterion (heart rate increase by 31 bpm), despite regular cardiovascular exer
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [40] source
It may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSAdministration of atomoxetine, a selective norepinephrine reuptake inhibitor, significantly increased the standing heart rate (from 105 bpm to 121 bpm) in POTS patients and resulted in greater symptoms of orthostatic intolerance.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [46] source
It may state two separate claims as one.
Premisecitation§ Treatment for Partial Autonomic NeuropathyMidodrine time to peak concentration is 1 h after administration, and pharmacologic effects last 4-5 h.
“Time to peak concentration is 1 h after administration, and pharmacologic effects last 4-5 h (55).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [55] source
It may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSIatrogenic inhibition of the norepinephrine transporter has been shown to engender a POTS-like state, increase upright heart rate, and exacerbate symptoms in POTS patients.
“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).”
Quote in the paperNot a substantial claim0 of 4 sources checkedIt may state two separate claims as one.
Premisecitation§ Treatment for Partial Autonomic NeuropathyOctreotide can reduce orthostatic tachycardia in POTS patients to a similar extent as midodrine, but it lacks a widely available oral dosage form and must be administered subcutaneously.
“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).”
Quote in the paperNot a substantial claim0 of 2 sources checkedIt may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSLevels 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 approximately 400-500 pg/ml.
“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).”
Quote in the paperSubstantial claim0 of 2 sources checkedIt may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSShannon et al. 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.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] source
It may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSAdministration of a selective serotonin reuptake inhibitor, sertraline, also appeared to acutely worsen symptoms in POTS patients, possibly due to nonselective inhibition of the norepinephrine transporter.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] source
It may state two separate claims as one.
Interpretationreasoning§ Hyperadrenergic POTSAlthough elevated norepinephrine state may be secondary to partial autonomic neuropathy or hypovolemia, the hallmark of hyperadrenergic POTS is primary adrenergic excess.
“Although this elevated norepinephrine state may be secondary to partial autonomic neuropathy or hypovolemia, the hallmark of this endophenotype is primary adrenergic excess.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ Treatment for Partial Autonomic NeuropathyDroxidopa is an orally active, synthetic prodrug of norepinephrine that reaches peak plasma concentration in 2 h.
“Droxidopa is an orally active, synthetic prodrug of norepinephrine that reaches peak plasma concentration in 2 h (57).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [57] source
It may state two separate claims as one.
Premisecitation§ Treatment for Partial Autonomic NeuropathyThis dose of midodrine did not cause hypertension nor significantly elevate blood pressure in this patient population.
“Moreover, this dose did not cause hypertension nor significantly elevate blood pressure in this patient population (54).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [54] source
It may state two separate claims as one.
Interpretationreasoning§ Hypovolemic POTSThe renin-aldosterone paradox and dysregulation of RAAS play a central role in the pathogenesis of the hypovolemic POTS endophenotype, and would be worsened in the setting of any deconditioning.
“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.”
Quote in the paperSubstantial claim- 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.
It may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSIn healthy subjects, the supine plasma norepinephrine level is approximately 200 pg/ml, and upon standing, it doubles before it plateaus after 7.5 min.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] source
It may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSEach twin had normal levels of supine plasma norepinephrine (269 pg/ml and 199 pg/ml), but standing plasma norepinephrine exceeded 900 pg/ml.
“Each twin had normal levels of supine plasma norepinephrine (269 pg/ml and 199 pg/ml), but standing plasma norepinephrine exceeded 900 pg/ml.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] source
It may state two separate claims as one.
Premisecitation§ Hyperadrenergic POTSFedorowski et al. 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.
“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.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] source
It may state two separate claims as one.
Premisecitation§ Treatment for Partial Autonomic NeuropathyDroxidopa has not been well studied prospectively, and a retrospective analysis demonstrated only modest improvement in symptoms.
“It has not been well studied prospectively, and a retrospective analysis demonstrated only modest improvement in symptoms (58).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] source
It may state two separate claims as one.
Premisecitation§ Treatment for Hypovolemic POTSExercise is the only intervention that has been shown to improve the aldosterone:renin ratio and increase plasma and blood volumes chronically.
“Exercise is the only intervention that has been shown to improve the aldosterone:renin ratio and increase plasma and blood volumes chronically (64).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [64] source
It may state two separate claims as one.
Premisecitation§ Treatment for Hypovolemic POTSPOTS 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.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42] source
It may state two separate claims as one.
Premisecitation§ Treatment for Hyperadrenergic POTSIn studies of ivabradine, 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%.
“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).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. It may be too vague to check against evidence.
Interpretationnone given§ CONCLUSIONThe clinically heterogeneous nature of POTS makes management inherently difficult.
“The clinically heterogeneous nature of POTS makes management inherently difficult.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Premisecitation§ Treatment for Hypovolemic POTSPOTS patients taking DDAVP noted significant improvements in overall symptoms, specifically symptoms related to vision, tremulousness, and palpitations.
“Patients also noted significant improvements in overall symptoms, specifically symptoms related to vision, tremulousness, and palpitations (69).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [69] source
It may state two separate claims as one.
Premisecitation§ Treatment for Hyperadrenergic POTSPropranolol (instant release) at 20 mg significantly reduced orthostatic tachycardia and improved symptoms compared to placebo up to 4 h after administration in POTS patients.
“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.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [78] source
It may state two separate claims as one.
Premisecitation§ CONCLUSIONMany POTS patients 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.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
It may state two separate claims as one.
Premisecitation§ Treatment for Hypovolemic POTSErythropoietin improved symptoms in one study of treatment-refractory POTS patients, at the expense of elevating blood pressure.
“but it did improve symptoms, at the expense of elevating blood pressure, in one study of treatment-refractory POTS patients (72).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [72] source
It may state two separate claims as one.
Premisecitation§ Treatment for Hyperadrenergic POTSPyridostigmine enhances cholinergic activity at both ganglionic nicotinic and postganglionic muscarinic acetylcholine receptors, with a likely net increase in parasympathetic nervous system tone.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] source
Probably not a substantial claim. It may be too vague to check against evidence.
Interpretationcitation§ CONCLUSIONImproving clinician awareness can help improve the shortcomings in POTS diagnosis.
“Improving clinician awareness can help improve all of these shortcomings (4).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] source
It may state two separate claims as one.
Interpretationreasoning§ Treatment for Hypovolemic POTSLack of strong data and the high expense of erythropoietin limit its routine use in the treatment of POTS.
“Lack of strong data and the high expense of erythropoietin limit its routine use in the treatment of POTS.”
Quote in the paperSubstantial claim
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
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The neuropathic postural tachycardia syndrome
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Cardiac Atrophy After Bed-Rest Deconditioning: A Nonneural Mechanism for Orthostatic Intolerance
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Cardiac origins of the postural orthostatic tachycardia syndrome
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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
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Self-citationAutoimmune Basis for Postural Tachycardia Syndrome
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Self-citationRaj, S. R., Black, B. K., Biaggioni, I., Paranjape, S. Y., Ramirez, M., Dupont, W. D., & Robertson, D. (2009) · Circulation · doi:10.1161/circulationaha.108.846501 · Cited by 225 · cited 1×
“(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.”
BackgroundSelf-citationHyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders
Shibao, C., Arzubiaga, C., Roberts, L. J., Raj, S., Black, B., Harris, P., & Biaggioni, I. (2005) · Hypertension · doi:10.1161/01.hyp.0000158259.68614.40 · Cited by 220
Self-citationEffects of volume loading and pressor agents in idiopathic orthostatic tachycardia
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“Acute infusions of normal saline have been shown to afford rapid relief in patients with POTS crisis (8, 54), but this approach is not sustainable in the long-term due to the potential for vascular access complications (67).”
BackgroundHuman muscle sympathetic neural and haemodynamic responses to tilt following spaceflight
Levine, B. D., Pawelczyk, J. A., Ertl, A. C., Cox, J. F., Zuckerman, J. H., Diedrich, A., Biaggioni, I., Ray, C. A., Smith, M. L., Iwase, S., et al. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.012575 · Cited by 191
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Exercise and non-pharmacological treatment of POTS
Fu, Q., & Levine, B. D. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.07.001 · Cited by 174
Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome
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Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome
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Postural tachycardia syndrome: beyond orthostatic intolerance
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Antiadrenergic autoimmunity in postural tachycardia syndrome
Fedorowski, A., Li, H., Yu, X., Koelsch, K. A., Harris, V. M., Liles, C., Murphy, T. A., Quadri, S. M. S., Scofield, R. H., Sutton, R., et al. (2017) · EP Europace · doi:10.1093/europace/euw154 · Cited by 151 · cited 3×
“Higher levels of autoantibodies against beta-1 and beta-2 adrenoreceptors have been detected in POTS patients versus healthy controls in serologic studies (32, 44).”
BackgroundStewart, J. M. (2002) · Circulation · doi:10.1161/01.cir.0000016348.55378.c4 · Cited by 138
Effect of standing on neurohumoral responses and plasma volume in healthy subjects
Jacob, G., Ertl, A. C., Shannon, J. R., Furlan, R., Robertson, R. M., & Robertson, D. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.3.914 · Cited by 134 · cited 1×
“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).”
BackgroundPostural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome
Roma, M., Marden, C. L., De Wandele, I., Francomano, C. A., & Rowe, P. C. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.02.006 · Cited by 133
Psychiatric profile and attention deficits in postural tachycardia syndrome
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Selective Norepinephrine Reuptake Inhibition as a Human Model of Orthostatic Intolerance
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Deconditioning in patients with orthostatic intolerance
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Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience
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“Further studies have also demonstrated long-term benefits with using pyridostigmine in POTS patients (81, 82).”
BackgroundSingle centre experience of ivabradine in postural orthostatic tachycardia syndrome
McDonald, C., Frith, J., & Newton, J. L. (2011) · Europace · doi:10.1093/europace/euq390 · Cited by 105
Ocon, A. J., Medow, M. S., Taneja, I., Clarke, D., & Stewart, J. M. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00138.2009 · Cited by 105
Vincent, S., Bieck, P. R., Garland, E. M., Loghin, C., Bymaster, F. P., Black, B. K., Gonzales, C., Potter, W. Z., & Robertson, D. (2004) · Circulation · doi:10.1161/01.cir.0000130847.18666.39 · Cited by 102
Regional blood volume and peripheral blood flow in postural tachycardia syndrome
Stewart, J. M., & Montgomery, L. D. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00086.2004 · Cited by 102
Anderson, J. W., Lambert, E. A., Sari, C. I., Dawood, T., Esler, M. D., Vaddadi, G., & Lambert, G. W. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00230 · Cited by 96 · cited 1×
“Given the high incidence of polypharmacy in POTS patients (10), coupled with the perception of increased depression in POTS patients (74), antidepressant use is likely high in this patient population.”
BackgroundPersistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome
Stewart, J. M., Medow, M. S., Glover, J. L., & Montgomery, L. D. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00784.2005 · Cited by 95
Masuki, S., Eisenach, J. H., Johnson, C. P., Dietz, N. M., Benrud-Larson, L. M., Schrage, W. G., Curry, T. B., Sandroni, P., Low, P. A., & Joyner, M. J. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00927.2006 · Cited by 91
Pharmacotherapy for postural tachycardia syndrome
Miller, A. J., & Raj, S. R. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.04.008 · Cited by 91
Self-citationPOTS versus deconditioning: the same or different?
Joyner, M. J., & Masuki, S. (2008) · Clinical Autonomic Research · doi:10.1007/s10286-008-0487-7 · Cited by 90
Coffin, S. T., Black, B. K., Biaggioni, I., Paranjape, S. Y., Orozco, C., Black, P. W., Dupont, W. D., Robertson, D., & Raj, S. R. (2012) · Heart Rhythm · doi:10.1016/j.hrthm.2012.05.002 · Cited by 88
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Okamoto, L. E., Diedrich, A., Baudenbacher, F. J., Harder, R., Whitfield, J. S., Iqbal, F., Gamboa, A., Shibao, C. A., Black, B. K., Raj, S. R., et al. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07199 · Cited by 79
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Ross, A. J., Ocon, A. J., Medow, M. S., & Stewart, J. M. (2014) · Clinical Science · doi:10.1042/cs20130222 · Cited by 78
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Decreased Microvascular Nitric Oxide–Dependent Vasodilation in Postural Tachycardia Syndrome
Medow, M. S., Minson, C. T., & Stewart, J. M. (2005) · Circulation · doi:10.1161/circulationaha.104.526764 · Cited by 74
Splanchnic-mesenteric capacitance bed in the postural tachycardia syndrome (POTS)
Tani, H., Singer, W., McPhee, B. R., Opfer-Gehrking, T. L., Haruma, K., Kajiyama, G., & Low, P. A. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00205-8 · Cited by 71
Local vascular responses affecting blood flow in postural tachycardia syndrome
Stewart, J. M., Medow, M. S., & Montgomery, L. D. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00429.2003 · Cited by 71
Segmental orthostatic fluid shifts
Diedrich, A., & Biaggioni, I. (2004) · Clinical Autonomic Research · doi:10.1007/s10286-004-0188-9 · Cited by 70
Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome
Stewart, J. M., Medow, M. S., Minson, C. T., & Taneja, I. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00600.2007 · Cited by 68
Effects of Norepinephrine Reuptake Inhibition on Postural Tachycardia Syndrome
Green, E. A., Raj, V., Shibao, C. A., Biaggioni, I., Black, B. K., Dupont, W. D., Robertson, D., & Raj, S. R. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000395 · Cited by 64
Self-citationAbnormalities of angiotensin regulation in postural tachycardia syndrome
Mustafa, H. I., Garland, E. M., Biaggioni, I., Black, B. K., Dupont, W. D., Robertson, D., & Raj, S. R. (2011) · Heart Rhythm · doi:10.1016/j.hrthm.2010.11.009 · Cited by 62
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Acetylcholinesterase Inhibition in Patients With Orthostatic Intolerance
Singer, W., Opfer-Gehrking, T. L., Nickander, K. K., Hines, S. M., & Low, P. A. (2006) · Journal of Clinical Neurophysiology · doi:10.1097/01.wnp.0000229946.01494.4c · Cited by 60
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Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome
Bayles, R., KN, H., Lambert, E., Baker, E. K., Agrotis, A., Guo, L., Jowett, J. B. M., Esler, M., Lambert, G., & El-Osta, A. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.111.244343 · Cited by 56 · cited 1×
“Another study demonstrated that epigenetic modification of the SCL6A2 gene resulting in its downregulation was more prevalent in POTS patients than in healthy controls (45).”
BackgroundStewart, J. M., Pianosi, P., Shaban, M. A., Terilli, C., Svistunova, M., Visintainer, P., & Medow, M. S. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.008854 · Cited by 55
Effects of exercise training on arterial-cardiac baroreflex function in POTS
Galbreath, M. M., Shibata, S., VanGundy, T. B., Okazaki, K., Fu, Q., & Levine, B. D. (2011) · Clinical Autonomic Research · doi:10.1007/s10286-010-0091-5 · Cited by 54
Stewart, J. M., & Weldon, A. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.4.1505 · Cited by 53
Neuronal and hormonal perturbations in postural tachycardia syndrome
Mar, P. L., & Raj, S. R. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00220 · Cited by 52
Self-citationIvabradine in the treatment of postural tachycardia syndrome (POTS), a single center experience
Ruzieh, M., Sirianni, N., Ammari, Z., Dasa, O., Alhazmi, L., Karabin, B., & Grubb, B. (2017) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.13182 · Cited by 46
Mustafa, H. I., Raj, S. R., Diedrich, A., Black, B. K., Paranjape, S. Y., Dupont, W. D., Williams, G. H., Biaggioni, I., & Robertson, D. (2012) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.111.965343 · Cited by 44
Self-citationReflex vascular defects in the orthostatic tachycardia syndrome of adolescents
Stewart, J. M., & Weldon, A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.6.2025 · Cited by 43
Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome
Ruzieh, M., Dasa, O., Pacenta, A., Karabin, B., & Grubb, B. (2017) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000000468 · Cited by 42
Zhao, J., Du, S., Yang, J., Lin, J., Tang, C., Du, J., & Jin, H. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.05.039 · Cited by 41
Moon, J., Kim, D.-Y., Lee, W.-J., Lee, H. S., Lim, J.-A., Kim, T.-J., Jun, J.-S., Park, B., Byun, J.-I., Sunwoo, J.-S., et al. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0612-9 · Cited by 40
Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype?
Miglis, M. G., Schultz, B., & Muppidi, S. (2017) · Autonomic Neuroscience · doi:10.1016/j.autneu.2017.10.001 · Cited by 38
Treatment of orthostatic tachycardia with erythropoietin
Hoeldtke, R. D., Horvath, G. G., & Bryner, K. D. (1995) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)80230-7 · Cited by 38
Postural orthostatic tachycardia syndrome and the potential role of mast cell activation
Doherty, T. A., & White, A. A. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.05.001 · Cited by 37 · cited 1×
“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).”
BackgroundGaffney, F. A., Lane, L. B., Pettinger, W., & Blomqvist, C. G. (1983) · Chest · doi:10.1378/chest.83.2.436 · Cited by 36
Ivabradine for the Treatment of Postural Orthostatic Tachycardia Syndrome: A Systematic Review
Gee, M. E., Watkins, A. K., Brown, J. N., & Young, E. (2018) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-017-0252-1 · Cited by 35
Moak, J. P., Leong, D., Fabian, R., Freedenberg, V., Jarosz, E., Toney, C., Hanumanthaiah, S., & Darbari, A. (2016) · Pediatric Cardiology · doi:10.1007/s00246-015-1274-6 · Cited by 34
Erythropoietin in the Treatment of Postural Orthostatic Tachycardia Syndrome
Kanjwal, K., Saeed, B., Karabin, B., Kanjwal, Y., Sheikh, M., & Grubb, B. P. (2012) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e3181ef621a · Cited by 34
Orthostatic heart rate responses after prolonged space flights
Tank, J., Baevsky, R. M., Funtova, I. I., Diedrich, A., Slepchenkova, I. N., & Jordan, J. (2011) · Clinical Autonomic Research · doi:10.1007/s10286-010-0106-2 · Cited by 32
Kpaeyeh, J., Mar, P. L., Raj, V., Black, B. K., Arnold, A. C., Biaggioni, I., Shibao, C. A., Paranjape, S. Y., Dupont, W. D., Robertson, D., et al. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000221 · Cited by 29
Self-citationZhao, J., Tang, C., Jin, H., & Du, J. (2014) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2014.04.032 · Cited by 27
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Self-citationMoving from the present to the future of Postural Tachycardia Syndrome – What we need
Raj, S. R., & Robertson, D. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.06.007 · Cited by 22
Self-citationRow, row, row your way to treating postural tachycardia syndrome
Raj, S. R. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.12.039 · Cited by 20
Self-citationDel Pozzi, A. T., Pandey, A., Medow, M. S., Messer, Z. R., & Stewart, J. M. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00194.2014 · Cited by 17
Patel, D. P., Nair, S., Suhagia, B. N., & Patel, B. M. (2016) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2016.09.005 · Cited by 15
Wang, H., Yang, G., Zhou, J., Pei, J., Zhang, Q., Song, X., & Sun, Z. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.04.056 · Cited by 12
Zhang, Z.-Y., Qian, L.-L., & Wang, R.-X. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00698 · Cited by 12
SANTOS, R. Q. D., SMIDT, L., SUZIGAN, B. H., DE SOUZA, L. V., & BARBISAN, J. N. (2013) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12069 · Cited by 9
Flagged first, then by citations
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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 736
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., & Padda, I. (2022) · Current problems in cardiology · doi:10.1016/j.cpcardiol.2022.101384 · Cited by 33
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 16
“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 16
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., Hasbani, G. E., Eldine, M. N., Nour-Eldine, W., Taher, A., & Uthman, I. (2021) · Revue neurologique (Paris) · doi:10.1016/j.neurol.2021.10.006 · Cited by 5
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
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“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 6
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
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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
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“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
Waheed, W., & Holmes, G. L. (2024) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2024.09.025 · Cited by 2
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 1
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.”
Saunders, D., Arnold, T. B., Lavender, J. M., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2790711/v1 · Cited by 1
Novel pharmacotherapeutic options for the treatment of postural orthostatic tachycardia syndrome
Ngonge, A. L., Nyange, C., & Ghali, J. K. (2024) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2024.2319224 · Cited by 1
“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
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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Treatment of Headache in Children and Adolescents with POTS
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Self-citationGut hormones in POTS and their relation to hemodynamic parameters and gastrointestinal symptoms
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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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