Postural orthostatic tachycardia syndrome (POTS) …

Douglas J Lanska MD MS MSPH

Neuro-Ophthalmology & Neuro-Otology

Updated 05.20.2024
Released 02.20.2008
Expires For CME 05.20.2027

Postural orthostatic tachycardia syndrome

Author: Douglas J Lanska MD MS MSPH

See Contributor Disclosures

Postural orthostatic tachycardia syndrome

In This Article

Quick Link

Introduction

Overview

The author explains the clinical presentation, pathophysiology, diagnostic workup, and management of postural orthostatic tachycardia syndrome (POTS), an often disabling syndrome of symptomatic orthostatic tachycardia in the absence of orthostatic hypotension. POTS is a restricted sympathetic dysautonomia with neuropathic and central forms resulting from a constellation of different disorders. Although there is no universally effective therapy for postural orthostatic tachycardia syndrome, pharmacological treatment can include beta-blocking agents to blunt orthostatic increases in heart rate, alpha-adrenergic agents to increase peripheral vascular resistance, mineralocorticoid agents to increase blood volume, and serotonin reuptake inhibitors.

Key points

	• Postural orthostatic tachycardia syndrome is an often-disabling syndrome of symptomatic orthostatic tachycardia in the absence of orthostatic hypotension.
	• POTS is a restricted sympathetic dysautonomia with neuropathic and central forms resulting from a constellation of different disorders.
	• The symptoms of postural orthostatic tachycardia syndrome suggest a hyperadrenergic state and impaired cerebral perfusion.
	• In addition to the orthostatic tachycardia, physical findings in postural orthostatic tachycardia syndrome can include a murmur or click of mitral valve prolapse (although significant mitral regurgitation is unusual) and prominent dependent acrocyanosis.
	• There is no universally effective therapy for postural orthostatic tachycardia syndrome.
	• Nonpharmacological treatment can include increasing fluid/salt intake, increasing aerobic exercise, lower-extremity strength training, and compression stockings, as well as counseling and training for management of pain or anxiety and family education.
	• Pharmacological treatment can include beta-blocking agents to blunt orthostatic increases in heart rate, alpha-adrenergic agents to increase peripheral vascular resistance, mineralocorticoid agents to increase blood volume, and serotonin reuptake inhibitors.

Historical note and terminology

Postural orthostatic tachycardia syndrome is an often disabling syndrome of symptomatic orthostatic tachycardia in the absence of orthostatic hypotension. POTS is a restricted sympathetic dysautonomia with neuropathic and central forms resulting from a constellation of different disorders. The syndrome has also been called orthostatic tachycardia, orthostatic intolerance, idiopathic orthostatic intolerance and postural tachycardia, neurocirculatory asthenia, mitral valve prolapse syndrome, irritable heart, and soldier’s heart, among others. There is also clinical overlap with chronic fatigue syndrome, especially in adolescent cases (158; 105; 108; 131), although patients with both conditions apparently represent a specific subset of those with chronic fatigue syndrome (131).

Clinical manifestations

Presentation and course

	• Patients with POTS are mainly young (aged between 15 years and 40 years) and are predominantly female.
	• POTS has been associated with a wide variety of conditions, including diabetes, some autoimmune disorders, infections, trauma, surgery, stress, mastocytosis, and the hypermobility type of Ehlers-Danlos syndrome.
	• Palpitations, dizziness, and other symptoms of POTS occur mainly when standing upright and are typically relieved by sitting or lying flat.
	• Presyncope is common with POTS but less than a third of the patients experience syncope.
	• Orthostatic headache, when present in POTS, tends to be bifrontal, bitemporal, or holocephalic but occasionally may have a nuchal or occipital distribution, clearly distinct from the “coat-hanger” distribution sometimes seen with orthostatic hypotension and then attributed to trapezius ischemia.
	• Orthostatic headache affects approximately two thirds of patients with POTS, especially among those younger than 30 years of age.
	• Symptoms not attributable to orthostatic intolerance include functional gastrointestinal or bladder disorders, chronic headache, fibromyalgia, and sleep disturbances.

Patients with POTS are mainly young (aged between 15 years and 40 years) and are predominantly female (87; 167; 172; 184). A typical patient is a female of childbearing age, who often first displays symptoms in adolescence (172; 184). Disease onset may be precipitated by immunological stressors (eg, viral infection) (172). Exacerbating factors can include exertion, food ingestion, and elevated ambient temperatures (87).

A single-institution survey study evaluated the most common occurring symptoms in patients with POTS, symptoms with greatest impact on quality of life in patients with POTS, and symptoms that lead to emergency department visits in patients with POTS (22).

Most common occurring symptoms in patients with POTS

(Source: Cooperrider J, Kriegler J, Yunus S, Wilson R. A survey-based study examining differences in perception of postural orthostatic tachycardia syndrome between patients and primary care physicians. Cureus 2022;14[10]:e3016...
Symptoms with greatest impact on quality of life in patients with POTS

(Source: Cooperrider J, Kriegler J, Yunus S, Wilson R. A survey-based study examining differences in perception of postural orthostatic tachycardia syndrome between patients and primary care physicians. Cureus 2022;14[10]:e3016...
Symptoms that lead to emergency department visits in patients with POTS

(Source: Cooperrider J, Kriegler J, Yunus S, Wilson R. A survey-based study examining differences in perception of postural orthostatic tachycardia syndrome between patients and primary care physicians. Cureus 2022;14[10]:e3016...

Palpitations, dizziness, and other symptoms of POTS occur mainly when standing upright and are typically relieved by sitting or lying flat. Lightheaded dizziness is the most common symptom and indeed is almost always present and the most disruptive of quality of life (04). The symptoms of postural orthostatic tachycardia syndrome suggest a hyperadrenergic state and impaired cerebral perfusion. Presyncope is common with POTS, but less than a third of the patients experience syncope (120). Chest discomfort may be a feature, but it is not associated with coronary artery stenosis (120). Orthostatic headache, when present in POTS, tends to be bifrontal, bitemporal, or holocephalic but occasionally may have a nuchal or occipital distribution, clearly distinct from the “coat-hanger” distribution sometimes seen with orthostatic hypotension and then attributed to trapezius ischemia (94). Orthostatic headache affects approximately two thirds of patients with POTS, especially among those younger than 30 years of age (74). Fatigue and palpitations on assuming an upright posture are very common (68; 105; 108).

Symptoms not attributable to orthostatic intolerance include functional gastrointestinal or bladder disorders, chronic headache, fibromyalgia, and sleep disturbances (11; 185; 169). Gastrointestinal symptoms are more significantly prevalent and severe in POTS than in controls, with nausea being the most prevalent (79% vs. 5%) and bloating and flatulence being the most severe (169). Bowel irregularities are common, and many patients are co-diagnosed with irritable bowel syndrome (169). Investigations of the gastrointestinal symptoms in POTS are conflicting with some studies reporting delayed gastric emptying and delayed colonic transit in most patients (58; 185), whereas others report that rapid gastric emptying is more common than delayed gastric emptying (112; 82). However, gastric emptying disturbances were not significantly associated with gastrointestinal symptoms, autonomic symptoms, or measured autonomic dysfunction (112). A quarter of POTS patients have delayed small bowel transit with hypocontractility patterns within the small bowel, including decreased contractions/minute and a decreased motility index (185). Persistent, gastrointestinal symptoms and disease severity are significantly associated with the serum level of antimuscarinic acetylcholine receptor (mAChRs) antibodies (163).

Almost all patients with POTS and orthostatic headache also have nonorthostatic headaches fitting criteria for migraine (74). Patients with POTS also have higher subjective daytime sleepiness and worse sleep and health-related quality of life (09; 184).

Table 1. Symptoms of Postural Orthostatic Tachycardia Syndrome (Particularly When Upright)

• Tachycardia (postural)
• Palpitations
• Chest discomfort
• Dyspnea
• Tremulousness
• Exaggerated physiological tremor
• Cold sweaty extremities
• Fatigue
• Exercise intolerance
• Lightheaded dizziness, presyncope, and syncope
• Blurred or tunnel vision
• Headache, possibly migrainous
• Mental clouding (feeling “in a fog”; “brain fog”)
• Nausea
• Bowel irregularities
• Abdominal discomfort

Table 2. Diagnostic Criteria for Postural Orthostatic Tachycardia Syndrome

	• Sustained heart rate increase of at least 30 beats per minute (40 beat per minute in children) from supine to standing within 10 minutes of standing (or a heart rate that exceeds 120 bpm on standing)
	• Lack of orthostatic hypotension (systolic blood pressure does not fall by more than 20 mmHg and may increase with standing)
	• Symptoms of orthostatic intolerance (eg, lightheadedness, weakness, palpitations, blurred vision, breathing difficulties, nausea, or headache) develop with standing and resolve with recumbency
	• Symptoms present for at least 3 months
	• Occurs in the absence of prolonged bed rest (deconditioning)
	• Occurs in the absence of medications that impair autonomic regulation (eg, vasodilators, diuretics, antidepressants, anxiolytic agents)
	• Occurs in the absence of other conditions that might cause autonomic failure or orthostatic tachycardia (eg, active bleeding, anemia, dehydration)
(120; 90; 168; 64; 68; 65; 184)

Clinical diagnostic criteria have been proposed (120; 90; 168; 64; 68). These criteria may not be applicable to children and adolescents (150; 23; 59), and, in particular, the heart rate criteria (≥30 bpm) for POTS are not appropriate in younger individuals (23). Higher postural heart rates in children do not predispose individuals to the development of POTS (23). In addition to the orthostatic tachycardia, physical findings in postural orthostatic tachycardia syndrome can include a murmur or click of mitral valve prolapse (although significant mitral regurgitation is unusual), prominent dependent acrocyanosis, and joint hyperextensibility (120; 111). Dependent acrocyanosis, present in about half of patients with POTS, is characterized by a dark reddish-blue discoloration of the legs, which are cold to the touch (120). This acrocyanosis is apparently due to decreased cutaneous blood flow rather than increased blood pooling in venous capacitance vessels (36; 154; 120).

Syncope (both with tilt table testing and clinically) occurs much more commonly in patients with postural tachycardia syndrome than in patients with orthostatic hypotension (106).

Symptoms may be exacerbated by fatigue, exercise, heat, dehydration, the postprandial state, menses, various medications, fibromyalgia, and migraine (168; 117; 153).

Although patients with postural orthostatic tachycardia syndrome may appear anxious, they do not have an increased lifetime prevalence of psychiatric disorders in general (127). Nevertheless, cognitive and behavioral factors, including somatic hypervigilance associated with anxiety and depression, may contribute to symptom chronicity and disability (11; 06). Indeed, orthostatic intolerance is significantly correlated with depression and diminished quality of life but not with the maximal heart rate increment (95). Patients with POTS report mild anxiety and moderate depressive symptoms and demonstrate severe somatization and elevated anxiety sensitivity (34). Patients with POTS have deficits in selective attention and cognitive processing, even in the seated position when orthostatic stress is minimized (06). Diminished cognitive performance in POTS is associated with slow oscillations in cerebral blood flow (156).

The debilitating nature of POTS predisposes patients to a high degree of functional impairment and decreased quality of life compared with sex- and age-matched individuals without POTS (38; 145; 04; 114; 184).

Prognosis and complications

Although outcomes are variable, most patients with POTS have a "relatively favorable" prognosis (75; 152). At 1 year of follow-up, orthostatic symptoms improve in most patients, and more than one third no longer fulfill tilt criteria, although changes in the magnitude of the posture-induced increment in heart rate are modest (75). About half of patients spontaneously recover within 1 to 3 years (31).

Six out of seven adolescents with POTS report resolved or improved symptoms--some only intermittent--when assessed an average of 5 years after initial treatment; adolescent patients with persistent symptoms at this point tend to have more physical than mental concerns (12).

Most patients are eventually able to resume their daily activities without marked limitations (152).

The course of POTS is variable during pregnancy and the postpartum period, but POTS did not appear to affect the rate of adverse pregnancy outcomes (96). Most women (81%) with POTS who become pregnant experience worsening of symptoms during pregnancy, especially in the first (63%) and third (59%) trimesters and 3 months after pregnancy (59%) (17). Most women with worsening symptoms in the first trimester also experienced worsening symptoms in the second (62%) and third (68%) trimesters, but if they improved in the first trimester then this improvement persisted throughout pregnancy (17). Of women who reported that POTS was triggered by a specific event (41%), 8% reported that pregnancy was the trigger (17).

Biological basis

• Neuropathic postural orthostatic tachycardia syndrome is thought to result from a restricted dysautonomia due to patchy or preferential sympathetic denervation of the blood vessels in the legs and kidney, whereas central hyperadrenergic POTS is thought to result from a primary excessive sympathetic nervous system discharge that secondarily affects the blood vessels, heart, and kidneys.

Anatomic localization

Neuropathic postural orthostatic tachycardia syndrome is thought to result from a restricted dysautonomia due to patchy or preferential sympathetic denervation of the blood vessels in the legs and kidney, whereas central hyperadrenergic POTS is thought to result from a primary excessive sympathetic nervous system discharge that secondarily affects the blood vessels, heart, and kidneys (160; 57; 143; 151; 120; 137). Neuropathic POTS is characterized by decreased adrenergic vasoconstriction, whereas hyperadrenergic POTS is characterized by increased adrenergic vasoconstriction (137).

Patients with postural orthostatic tachycardia syndrome develop symptoms of orthostatic intolerance before any change in cerebral perfusion is detected (129). In addition, cerebral autoregulation is preserved in POTS (142). However, cerebral hypoperfusion may occur with prolonged standing as a result of hypocapnia from hyperventilation (103).

The mechanism of orthostatic headaches in postural orthostatic tachycardia syndrome is unknown but may be caused by a relative CSF hypovolemia or reduced orthostatic CSF pressure (94); this may explain the empirically observed therapeutic response to volume expansion or application of abdominal binders.

Dependent edema when upright has been attributed to venous pooling in the lower extremities (161) and more recently to blunted arterial vasoconstriction causing passive redistribution of blood within venous capacitance beds (154) and increased microvascular filtration with increased arterial flow (155).

Some patients with postural orthostatic tachycardia syndrome have elevated levels of autoantibodies against the adrenergic alpha 1 receptor and the muscarinic acetylcholine M4 receptor (50).

Pathophysiology

Postural orthostatic tachycardia syndrome is a syndrome caused by a heterogeneous group of disorders with differing pathophysiologies (159; 94; 120; 64; 99; 11; 65; 116). Proposed pathophysiological mechanisms (not necessarily mutually exclusive) have included hypovolemia (in some with a hypokinetic circulation maintained by a vasoconstricted state), decreased cerebral and peripheral blood flow, an abnormality of brainstem regulation, lower limb dysautonomia as part of a limited length-dependent small-fiber autonomic neuropathy (with intact cardiac autonomic innervation), disturbed sympathetic-parasympathetic balance, impaired sympathetically mediated vasoconstriction, a deficient or dysfunctional norepinephrine transporter, (possibly in some cases as a result of epigenetic modification of the norepinephrine transporter gene), a hyperadrenergic state with increased sympathetic drive, impairments in the renin-angiotensin-aldosterone system, impaired endothelial nitrous oxide-mediated functions, beta-adrenergic receptor supersensitivity, deconditioning, volume dysregulation, an autonomic cardiac neuropathy, and a small heart size (so-called "Grinch syndrome") with reduced blood volume (35; 62; 61; 60; 80; 146; 173; 94; 121; 43; 126; 39; 51; 10; 11; 182). Deconditioning is present in almost all patients with POTS and may play a central role in the pathophysiology (113) and also in the persistence of symptoms over time.

Several distinct pathophysiological subtypes of postural orthostatic tachycardia syndrome have been recognized, including neuropathic and central hyperadrenergic forms (120; 65).

Neuropathic postural orthostatic tachycardia syndrome is thought to result from a restricted dysautonomia due to patchy or preferential sympathetic denervation, particularly of the blood vessels in the legs and kidney, with resultant hypovolemia and increased orthostatic venous pooling, and a secondary compensatory increase of sympathetic nervous system outflow (160; 57; 143; 151; 120). A subset of neuropathic patients with POTS may have a mild small-fiber neuropathy with abnormalities of unmyelinated nerve fibers in the skin as well as reduced myocardial postganglionic sympathetic innervation (52). Patients with neuropathic POTS have normal sympathetic neuronal release of norepinephrine in the arms but less norepinephrine release and corresponding sympathetic activation in the legs (61). Patients with POTS and hypovolemia also have inappropriately low levels of standing plasma rennin activity and aldosterone compared with normovolemic patients, indicating disruption of the renin-angiotensin-aldosterone axis contributing to hypovolemia and impaired sodium retention, possibly from impaired sympathetic modulation of renin release due to partial sympathetic denervation involving the kidney (120). Some patients with neuropathic POTS report symptom onset after a febrile illness (presumed to be an immune-mediated postviral autonomic neuropathy) or after pregnancy, immunizations, surgery, sepsis, or trauma (143; 120; 168). Ganglionic acetylcholine receptor antibodies are detectable in 10% to 15% of patients with neuropathic POTS (173; 168). POTS with acetylcholine receptor antibodies is a heterogeneous condition associated with preceding infection and high frequencies of syncope and fatigue (81). Persistent, gastrointestinal symptoms and disease severity are significantly associated with the serum level of antimuscarinic acetylcholine receptor (mAChRs) antibodies (163). Other cases of neuropathic POTS have recognized causes of autonomic neuropathy, including diabetes mellitus, amyloidosis, sarcoidosis, alcoholism, systemic lupus erythematosus, Sjögren syndrome, heavy metal intoxication, paraneoplastic neuropathies, and following some forms of chemotherapy (eg, with vinca alkaloids).

Central hyperadrenergic postural orthostatic tachycardia syndrome is an uncommon form of postural orthostatic tachycardia syndrome (representing approximately 10% of patients with POTS) thought to result from a primary excessive sympathetic nervous system discharge that secondarily affects the blood vessels, heart, and kidneys (66). Such patients often have extremely high upright norepinephrine levels, often higher than 1000 pg/ml and occasionally higher than 2000 pg/ml (120). Central hyperadrenergic POTS is often associated with orthostatic hypertension (120). At least some of these cases are due to dysfunction or blockage of the norepinephrine transporter that clears norepinephrine from the synaptic cleft. A norepinephrine transporter point mutation has been identified in a kindred with central hyperadrenergic POTS (OMIM #604715) (146; 134), and various drugs that inhibit the norepinephrine transporter (eg, most antidepressants and cocaine) are associated with marked orthostatic tachycardia and increased upright plasma norepinephrine concentrations; these drugs also profoundly reduce baroreflex control of sympathetic tone, increase responsiveness to vasoactive medications, and attenuate the response to sympathetic stimuli (144; 164).

Mast cell activation disorders may overlap with postural orthostatic tachycardia syndrome (147; 120; 65). Symptoms can include episodic flushing, dyspnea, headache, lightheadedness, dizziness, palpitations, excessive diuresis, nausea, vomiting, and diarrhea. Flushing can be triggered by prolonged standing, exercise, the premenstrual portion of the ovulatory cycle, meals, and sexual intercourse (120). Patients with mast cell activation disorders may also have a hyperadrenergic response to standing with both orthostatic tachycardia and hypertension. It is not clear whether mast cell activation produces a hyperadrenergic response via vasoactive mediators or whether sympathetic stimulation causes mast cell activation via release of norepinephrine and neuropeptide Y (07; 120).

The role of inflammatory mediators in POTS is unclear, but sympathetic activation in POTS is associated with increased circulating interleukin-6 in both lean and obese patients (107).

POTS has been associated with a wide variety of conditions, including diabetes, some autoimmune disorders, infections, trauma, surgery, stress, headache (including migraine), mastocytosis, Marfan syndrome, and the hypermobility type of Ehlers-Danlos syndrome (Table 3) (07; 147; 120; 87; 11; 176; 48; 65; 02; 24; 92; 91; 98; 128; 175; 25; 86; 97).

Although there are anecdotal reports of POTS developing after COVID-19 (due to severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) (24; 92; 91; 01; 45; 93; 101; 132; 19; 46; 165), some lay media reports have erroneously indicated—based on a single anecdotal report (91) and some follow-up commentary (24; 91)—that a significant proportion of patients with post-COVID-19 symptoms might be improved with treatment for POTS; so far, evidence that COVID-19 causes POTS at some significant level is lacking, although the nonspecific symptoms in prolonged COVID-19 patients include some with various dysautonomias that may include POTS. In adults, the prevalence of POTS is low in chronic fatigue syndrome, is not different from the rate in fatigued patients without chronic fatigue syndrome, and is not related to disease severity or treatment outcome (135).

Table 3. Conditions Associated with Postural Orthostatic Tachycardia

	Amyloidosis Anemia (iron deficiency) Autoimmune diseases
		• Autoimmune autonomic ganglionopathy • Sjögren syndrome • Systemic lupus erythematosus • Antiphospholipid syndrome • Celiac disease • Autoimmune/inflammatory syndrome induced by adjuvants (ASIA)
	Chiari malformation type I Diabetes mellitus (most frequent associated condition) Genetic disorders/abnormalities
		• Ehlers-Danlos syndrome • Storage diseases • Mitochondrial diseases • Marfan syndrome
	Infections
		• Viral diseases • Mononucleosis • Lyme disease • Extrapulmonary mycoplasma pneumonia • Hepatitis C • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19)
	Migraine Multiple sclerosis Mast cell activation disorders Paraneoplastic syndromes Pregnancy Sarcoidosis Surgery Toxicity
		• Alcoholism • Chemotherapy • Heavy metal poisoning
	Trauma Vaccinations Vitamin deficiencies

Although POTS is typically thought to be sporadic, familial cases have been identified (119). In affected families, autonomic dysfunction appears to be transmitted as an autosomal dominant trait with incomplete penetrance and a skewing of the sex ratio (119). Affected individuals are predominantly female (72% or approximately five of seven cases are female).

Atypical cases. Red flags for "atypical" POTS include older age at onset (50 years and older), male, prominent syncope, review of systems suggestive of specific alternative diagnoses, examination abnormalities other than joint hyperextensibility, or disease refractory to nonpharmacological and other first-line treatments (111). Although a limited evaluation is appropriate in POTS with typical features, an expanded and individualized workup has been recommended for atypical cases, including additional cardiac testing, autonomic testing, neuropathy workup, and autoimmune workup, depending on clinical presentation (111).

Epidemiology

	• Postural orthostatic tachycardia syndrome has a distinct female predominance, with about 80% of cases occurring in females.
	• Postural orthostatic tachycardia syndrome primarily affects women of childbearing age, with 80% to 90% of cases being women and most cases occurring between the ages of 15 and 50 years.
	• The prevalence ranges between 0.2% and 1.0% in developed countries.
	• There is a strong association between POTS and joint hypermobility or Ehlers-Danlos syndrome, although the significance of this has been seriously questioned.

Postural orthostatic tachycardia syndrome has a distinct female predominance, with about 80% of cases occurring in females (31; 172). The prevalence ranges between 0.2% and 1.0% in developed countries (31).

Postural orthostatic tachycardia syndrome primarily affects women of childbearing age, with 80% to 90% of cases being women and most cases occurring between the ages of 15 and 50 years (60; 133; 94; 120; 43; 168; 99; 14). Onset frequently occurs following pregnancy, major surgery or trauma, or presumed viral illness (120; 14). Symptoms in women are frequently exacerbated during the premenstrual phase of the ovulatory cycle (120). A smaller proportion (10% to 15%) has a family history of orthostatic intolerance (168).

There is a strong association between POTS and joint hypermobility or Ehlers-Danlos syndrome (136; 08; 15). In adolescents, over half have joint hypermobility (either Ehlers-Danlos syndrome or hypermobility spectrum disorder), and more than one third have a putative autoimmune or inflammatory trigger including infection, surgery, or trauma (14). However, “the purported association of these entities stems from an overlapping pool of vague, subjective symptoms, which is inadequate evidence to conclude that any such relationship exists” (77).

Anecdotal reports of POTS onset following COVID-19 infection (67; 13; 63; 110; 03; 53; 76; 27; 30; 32; 84; 138) or less commonly following vaccination for COVID-19 infection (130; 55; 139; 83) or improvement in POTS following COVID-19 infection (104) do not by themselves establish a causal association. The very fact that all these disparate anecdotes have been reported should cast sufficient doubt that they could all be causally related to COVID-19 or to vaccination for COVID-19. Formal epidemiologic studies (eg, case-control studies) are necessary to begin to establish such a causal relationship. Although a large cohort study did find a possible association between POTS and COVID-19 vaccination, there was a far stronger link with SARS-CoV-2 infection (78; 84; 138).

POTS has significant negative effects on employment, economic status, and quality of life for affected individuals, although existing studies are quite limited and appear biased by strong relationships with patient advocacy groups, even to the point of study design and execution (16).

Differential diagnosis

Confusing conditions

Numerous patients who do not meet criteria for postural orthostatic tachycardia syndrome are nevertheless given that diagnosis by providers for patients with postural symptoms without tachycardia, orthostatic tachycardia without symptoms, and those with orthostatic tachycardia but another overt cause for excessive tachycardia (125).

The differential diagnosis of POTS includes presyncopal dizziness (eg, orthostatic hypotension), disequilibrium, prolonged bed rest or deconditioning, medication-induced autonomic dysregulation, symptomatic secondary orthostatic tachycardia (eg, due to active bleeding, anemia, dehydration), hyperthyroidism, anxiety with hyperventilation syndrome or panic attacks, pheochromocytoma, multiple endocrine neoplasia type 2B, neurally mediated presyncope or syncope, chronic fatigue syndrome, and mitral valve prolapse syndrome (73; 120; 72).

Postural orthostatic tachycardia syndrome is often misdiagnosed as anxiety with hyperventilation syndrome or panic disorder, but much of the anxiety attributed to patients with POTS appears to be due to a misinterpretation of the physical (somatic) symptoms of a hyperadrenergic state (eg, palpitations) (120).

Paroxysmal hyperadrenergic symptoms can also occur in patients with pheochromocytoma, but (in comparison with postural orthostatic tachycardia syndrome patients) those with pheochromocytoma do not have clearly orthostatic symptoms, more commonly have symptoms while recumbent, generally have even higher plasma norepinephrine levels, and have elevated plasma free-metanephrines and urinary metanephrines (79; 28; 85; 49; 120; 170).

Associated or underlying disorders

Exacerbating factors can include exertion, food ingestion, and elevated ambient temperatures (87). POTS has been associated with a wide variety of conditions including diabetes, some autoimmune disorders, infections, trauma, surgery, stress, mastocytosis, and the hypermobility type of Ehlers-Danlos syndrome (Table 3) (07; 147; 120; 87; 11; 176; 48; 65; 02; 24; 92; 91).

Diagnostic workup

	• Supine norepinephrine levels are often at the high end of the normal range in patients with postural orthostatic tachycardia syndrome whereas standing norepinephrine levels are usually elevated (often more than 600 pg/ml), reflecting an increased sympathetic neural tone while upright.
	• Although some authorities have incorporated a standing norepinephrine level of higher than 600 pg/ml into diagnostic criteria, such levels occur in a minority of patients with POTS.
	• Blood volume is often low in postural orthostatic tachycardia syndrome patients.
	• EKG should be done to exclude an accessory bypass tract or cardiac conduction abnormalities and a Holter monitor helps exclude a reentrant dysrhythmia (especially in patients with paroxysmal tachycardia with sudden onset and offset).
	• The American Academy of Neurology’s Therapeutics and Technology Assessment Subcommittee has advocated clinical autonomic testing for patients with postural orthostatic tachycardia syndrome, although the supporting evidence for this recommendation as applied to clinical practice is limited.

Although diagnostic criteria have been developed for POTS, no single set of criteria is universally accepted (109).

Plasma norepinephrine levels should be measured in both supine and standing positions (after at least 15 to 30 minutes in each position). Supine norepinephrine levels are often at the high end of the normal range in patients with postural orthostatic tachycardia syndrome, whereas standing norepinephrine levels are usually elevated (often more than 600 pg/ml), reflecting an increased sympathetic neural tone while upright (120; 168). Although some authorities have incorporated a standing norepinephrine level of higher than 600 pg/ml into diagnostic criteria (120), such levels occur in a minority of patients with POTS (eg, 29% in the Mayo Clinic experience) (168). Plasma norepinephrine levels are not a perfect biomarker for sympathetic nervous system activity in general or in POTS because levels are affected by the release of norepinephrine from sympathetic neural activity and from adrenomedullary stimulation, leakage from storage vesicles, and by clearance (as a function, for example, of norepinephrine transporter activity) (43).

Blood volume is often low in postural orthostatic tachycardia syndrome patients (35; 62; 162; 121; 120; 126; 168). Low blood volume can be demonstrated with nuclear medicine tests that measure plasma volume or red cell volume. A low 24-hour urinary sodium excretion (less than 100 mEq of sodium per 24 hours) can also be used to indicate a low blood volume (29; 168).

Tilt-table testing is controversial for evaluation of patients with postural orthostatic tachycardia syndrome (120). Because the tilt-table test utilizes passive standing, the patients do not support their own weight or maintain balance and so do not utilize their “skeletal muscle pump.” Although the tilt-table test is fairly sensitive with a 30 bpm threshold for orthostatic tachycardia, it has a low specificity (less than 25%), with many control subjects developing orthostatic tachycardia with tilt-table testing (124; 120; 118).

EKG should be done to exclude an accessory bypass tract or cardiac conduction abnormalities and a Holter monitor helps exclude a reentrant dysrhythmia (especially in patients with paroxysmal tachycardia with sudden onset and offset) (120). MIBG myocardial scintigraphy may help distinguish patients with neuropathic POTS from patients with other forms of orthostatic intolerance (51).

The American Academy of Neurology’s Therapeutics and Technology Assessment Subcommittee has advocated clinical autonomic testing for patients with postural orthostatic tachycardia syndrome (05), although the supporting evidence for this recommendation as applied to clinical practice is limited. Patients with POTS often have an intense pressor response to Valsalva (120). Vagal function is usually preserved (147; 120). An associated mast cell activation disorder in patients with POTS and co-existent complaints of episodic flushing can be diagnosed by measuring urinary methylhistamines in individual 2-hour voids following a severe flushing spell (147; 120).

Management

	• There is no universally effective therapy for postural orthostatic tachycardia syndrome.
	• Management of POTS includes avoidance of precipitating factors, volume expansion, physical counter-measures, exercise training, pharmacotherapy, and behavioral-cognitive therapy.
	• Medications should be reviewed and any potentially contributory medications should be withdrawn, especially vasodilators, diuretics, yohimbine, and medications that inhibit the norepinephrine transporter (eg, many antidepressant and attention deficit disorder medications).
	• Potentially underlying causes of secondary POTS (eg, diabetes, amyloidosis) should be sought and treated.
	• Nonpharmacological treatment can include increasing fluid/salt intake, increasing aerobic exercise, lower-extremity strength training, and compression stockings, as well as counseling and training for management of pain or anxiety and family education.
	• Pharmacological treatment can include beta-blocking agents to blunt orthostatic increases in heart rate, alpha-adrenergic agents to increase peripheral vascular resistance, mineralocorticoid agents to increase blood volume, and serotonin reuptake inhibitors.

There is no universally effective therapy for postural orthostatic tachycardia syndrome. Management of POTS includes avoidance of precipitating factors, volume expansion, physical counter-measures, exercise training, pharmacotherapy, and behavioral-cognitive therapy. Existing medications should be reviewed, and any potentially contributory medications should be withdrawn, especially vasodilators, diuretics, yohimbine, and medications that inhibit the norepinephrine transporter (eg, many antidepressant and attention deficit disorder medications) (144; 174; 120). Potentially underlying causes of secondary POTS (eg, diabetes, amyloidosis) should be sought and treated.

Nonpharmacological treatments. Nonpharmacological treatment can include increasing fluid/salt intake, increasing aerobic exercise, lower-extremity strength training, and compression stockings, as well as counseling and training for management of pain or anxiety and family education (39; 40; 41; 64; 167; 114). Aggravating factors (eg, dehydration, extreme heat) should be avoided. Increasing fluid intake to 8 to 10 cups (2.0 to 2.5 liters) per day and increasing dietary salt to 200 to 300 mEq of sodium per day will help expand blood volume, but note that a liberal salt diet is usually insufficient to achieve this level of salt intake, so salt tablets (NaCl 1 gm taken orally, three times daily) may be required. Salt supplementation may improve symptoms, plasma volume, and orthostatic responses in patients with POTS (177). A 24-hour sodium excretion of less than 124 mmol per 24 hours is helpful as an indicator of the effectiveness of salt supplementation in children and adolescents (181). Regular light aerobic and resistance exercise is beneficial (178; 168; 39) and should be encouraged as it will also help decrease deconditioning and increase blood volume. However, vigorous exercise may aggravate symptoms because of intramuscular and cutaneous vasodilation that accompanies exercise and because there may be straining that increases intraabdominal and intrathoracic pressures and decreases venous return to the heart; prolonged fatigue is also a concern in these patients. A cautious escalation of exercise, maintaining the heart rate within the target range, will help avoid a counterproductive exacerbation of symptoms that could discourage further efforts. Moderate compression (30 to 40 mmHg) thigh-high stockings (or preferably either waist-high compression stockings or thigh-high compression stockings plus an abdominal binder with an application pressure of 20 mmHg to help compress the splanchnic circulation) will help minimize peripheral venous pooling and enhance venous return, cardiac filling, and cardiac output (120; 168). As in patients with orthostatic hypotension, such stockings are difficult to put on and are uncomfortable to wear, so compliance is often a problem. Similarly, abdominal binders are often poorly tolerated.

Compared with a sham device, an impedance threshold device to increase inspiratory resistance and increase negative intrathoracic pressure improves heart rate control in patients with POTS during head-up tilt for a brief period (10 minutes) (42). It remains to be seen whether this approach will have clinical utility.

A neck compression collar has also been reported to alleviate orthostatic symptoms in patients with POTS (102).

Pharmacological treatments. There are little high-quality data about the effectiveness of individual medications in the treatment of POTS (54; 171). No medications for POTS have been studied with well-designed, long-term, randomized clinical trials; therefore, no medications are presently approved by the U.S. Food and Drug Administration for treatment of POTS.

Fluid loading with an oral rehydration solution improved short-term orthostatic tolerance in a small, controlled study, suggesting that is a convenient, safe, and effective therapy for short-term relief of orthostatic intolerance (89).

Pharmacological treatment can include beta-blocking agents to blunt orthostatic increases in heart rate, alpha-adrenergic agents to increase peripheral vascular resistance, mineralocorticoid agents to increase blood volume, and serotonin reuptake inhibitors (64).

Limited randomized crossover trials, open-label trials, pharmacological properties, and clinical experience suggest that fludrocortisone, clonidine, midodrine, beta-blockers, pyridostigmine, and selective serotonin reuptake inhibitors provide partial relief in selected patients (37; 123; 56; 120; 168; 20; 40; 69; 167; 183; 166).

Other agents suggested to be helpful in improving orthostatic tolerance and some of the hemodynamic abnormalities of POTS include the following: erythropoietin, a hematopoietic growth factor and glycosylated protein hormone; desmopressin (DDAVP), a synthetic analogue of the naturally occurring hormone vasopressin that acts as an antidiuretic hormone to conserve water in the kidneys; octreotide, a somatomedin analogue; ivabradine, a selective sinus node blocker with no effect on blood pressure; and phenylephrine, an alpha-1-adrenergic agonist (154; 56; 70; 71; 88; 100; 21). Acute decompensation can be treated with intravenous saline (47; 120; 168).

When hypovolemia is known or strongly suspected, the mineralocorticoid fludrocortisone acetate (a synthetic aldosterone analogue) at a dose of 0.05 to 0.10 mg orally at bedtime can help expand plasma volume through sodium retention, in addition to other effects that act to increase peripheral resistance by increasing alpha-adrenergic receptor sensitivity. Fludrocortisone is generally used at night when the body experiences the greatest natriuresis and diuresis. At these doses, fludrocortisone is generally well tolerated, but side effects can include hypokalemia, hypomagnesemia, acne, supine hypertension, peripheral edema, congestive heart failure, exacerbation of peptic ulcer disease, hyperglycemia, and steroid myopathy. High-dose therapy is associated with an increased risk of sudden death. Acute volume loading with saline does not improve cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function (33).

Other agents that can be considered to help expand blood volume include desmopressin and erythropoietin.

Midodrine, an alpha-sympathomimetic drug, functions as a vasopressor in patients with neurogenic orthostatic hypotension or in postural orthostatic tachycardia syndrome. Midodrine is probably an effective treatment for the neuropathic form of POTS, but not for hyperadrenergic POTS (137). In adults, midodrine is administered orally at a dose of 2.5 to 10 mg, three times daily. The last dose should be taken 3 to 4 hours before bedtime to minimize supine hypertension. Side effects of midodrine include marked increases in supine hypertension, piloerection (goosebumps), paresthesias, pruritus (especially scalp), nausea, and urinary retention and hesitancy in males. Midodrine should be avoided or used with caution in patients with coexisting ischemic heart disease, cardiac dysrhythmias, or peripheral vascular disease. Midodrine is also used to treat children with POTS, but it is not universally effective (183); elevated levels of plasma copeptin (above 10.482 pmol/L) is a predictive biomarker for the likelihood of successful treatment of children with POTS using midodrine hydrochloride (183).

Central sympatholytic medications can be helpful in suppressing sympathetic nervous system tone in patients with the central hyperadrenergic form of postural orthostatic tachycardia syndrome. For example, clonidine, a presynaptic alpha2 receptor agonist that acts centrally to decrease sympathetic tone, can be tried at a dose of 0.05 to 0.2 mg orally two times a day, or alternatively methyldopa, a false neurotransmitter, can be tried at a dose of 125 to 250 mg orally three times a day (60; 120). Side effects of clonidine include erythema, xerostomia, dizziness, fatigue, and somnolence.

Low-dose beta-blockers, such as propranolol 10 to 20mg orally two to four times a day, can help with heart rate control but need to be used cautiously, especially at higher doses that may produce orthostatic hypotension and fatigue (120; 122; 40). Patients with elevated standing norepinephrine levels generally respond better to treatment with beta-blockers than those with lower standing norepinephrine levels (168; 180). Low-dose oral propranolol (20 mg orally) significantly decreases tachycardia and improves symptoms, whereas higher-dose propranolol (80 mg orally) may worsen symptoms (122).

In a study of the short-term efficacy of combined treatment with a reduced-osmolarity oral rehydration salt formulation and propranolol in children with POTS, the frequency of syncopal attacks was significantly reduced and the symptom scores for orthostatic intolerance were improved with this regimen (179).

Pyridostigmine has been found to be helpful in the treatment of neurogenic orthostatic hypotension (141; 148; 149; 140), has theoretical potential in postural orthostatic tachycardia syndrome because of its actions at the autonomic ganglia and peripheral muscarinic parasympathetic receptors, and has been reported in a randomized crossover trial to be helpful in patients with POTS (123; 120). By its peripheral actions, it helps to restrain the heart rate; and by its ganglionic effects, it may augment the cholinergic efferent limb of the baroreceptor reflex while standing (and yet have little if any effect on augmenting blood pressure while recumbent). Pyridostigmine dosages of 30 to 60 mg orally two times a day alone or in combination with propranolol have been recommended for patients with POTS (120; 69). Because of its cholinergic effects, pyridostigmine may exacerbate diarrhea-predominant irritable bowel symptoms and so be poorly tolerated in some patients with POTS, and only approximately half of patients can tolerate pyridostigmine for this reason (120; 69).

The safety and efficacy of ivabradine have been evaluated for POTS in a single, small, short-term, randomized cross-over trial in which it was safe and effective in significantly improving heart rate and quality of life in patients with hyperadrenergic POTS (166). Other available information on ivabradine in POTS comes from prospective open-label trials, retrospective cohort studies, and various case reports (26; 44). Ivabradine is a selective and specific inhibitor of the I(f) current in the sinoatrial and atrioventricular nodes that acts to decrease heart rate and myocardial oxygen consumption at rest and during exercise (26; 44). Ivabradine provided symptomatic relief of POTS without blood pressure lowering (26; 44). The most common side effects were dizziness, nausea, headache, and fatigue, but often did not result in discontinuation of treatment (44). A randomized controlled trial is needed, but for now ivabradine is an option for patients with POTS who have failed or are unable to tolerate other treatment options, especially for those with hyperadrenergic POTS (44; 166).

Surgical therapies. In intractable cases, atrioventricular node ablation and dual chamber pacemaker implantation has been anecdotally reported as helpful (100).

An anecdotal case has been reported in which resolution of POTS occurred after percutaneous alcohol sympatholysis at T2 for comorbid craniofacial hyperhidrosis, both conditions are considered disorders of sympathetic regulation (18).

Another anecdotal case has been reported in which resolution of POTS occurred after implantation of a vagal nerve stimulator for intractable childhood-onset epilepsy (115). An ongoing clinical trial is evaluating the effects of transdermal vagal nerve stimulation and POTS (115).

Media

References

01: Abbate G, De Iulio B, Thomas G, et al. Postural orthostatic tachycardia syndrome after COVID-19: a systematic review of therapeutic interventions. J Cardiovasc Pharmacol 2023;82(1):23-31. PMID 37094584
02: Aliyev F. Postural orthostatic tachycardia: a syndrome requiring detailed search for associated conditions. Turk Kardiyol Dern Ars 2017;45(3):214-6. PMID 28429687
03: Amekran Y, Damoun N, El Hangouche AJ. Postural orthostatic tachycardia syndrome and post-acute COVID-19. Glob Cardiol Sci Pract 2022;2022(1-2):e202213. PMID 36339677
04: Angeli AM, Salonen BR, Ganesh R, et al. Symptom presentation by phenotype of postural orthostatic tachycardia syndrome. Sci Rep 2024;14(1):205. PMID 38168762
05: Anonymous. Assessment: clinical autonomic testing. Therapeutics and Technology Assessment Subcommittee, American Academy of Neurology. Neurology 1996;46:873-80. PMID 8618715
06: Arnold AC, Haman K, Garland EM, et al. Cognitive dysfunction in postural tachycardia syndrome. Clin Sci (Lond) 2015;128(1):39-45. PMID 25001527
07: Arzubiaga C, Morrow J, Roberts LJ, Biaggioni I. Neuropeptide Y, a putative cotransmitter in noradrenergic neurons, induces mast cell degranulation but not prostaglandin D2 release. J Allergy Clin Immunol 1991;87:88-93. PMID 1825102
08: Atuesta-Rodriguez AJ, Medina-Velasquez YF, Motta O, Narvaez-Reyes MI, Rondon-Herrera F. Association between postural orthostatic tachycardia syndrome and joint hypermobility. Case Rep Cardiol 2021;2021:8875003. PMID 34055418
09: Bagai K, Song Y, Ling JF, et al. Sleep disturbances and diminished quality of life in postural tachycardia syndrome. J Clin Sleep Med 2011;7(2):204-10. PMID 21509337
10: Bayles R, Harikrishnan KN, Lambert E, et al. Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler Thromb Vasc Biol 2012;32(8):1910-6. PMID 22723437
11: Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc 2012;87(12):1214-25. PMID 23122672
12: Bhatia R, Kizilbash SJ, Ahrens SP, et al. Outcomes of adolescent-onset postural orthostatic tachycardia syndrome. J Pediatr 2016;173:149-53. PMID 26979650
13: Blitshteyn S, Whitelaw S. Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients. Immunol Res 2021;69(2):205-11. PMID 33786700
14: Boris JR, Bernadzikowski T. Demographics of a large paediatric postural orthostatic tachycardia syndrome program. Cardiol Young 2018;28(5):668-74. PMID 29357955
15: Boris JR, Bernadzikowski T. Prevalence of joint hypermobility syndromes in pediatric postural orthostatic tachycardia syndrome. Auton Neurosci 2021;231:102770. PMID 33388686
16: Bourne KM, Chew DS, Stiles LE, et al. Postural orthostatic tachycardia syndrome is associated with significant employment and economic loss. J Intern Med 2021;290(1):203-12. PMID 33586284
17: Bourne KM, Nerenberg KA, Stiles LE, et al. Symptoms of postural orthostatic tachycardia syndrome in pregnancy: a cross-sectional, community-based survey. BJOG 2023;130(9):1120-7. PMID 36908200
18: Brock M, Chung TH, Gaddam SR, Kathait AS, Ober C, Georgiades C. Resolution of postural orthostatic tachycardia syndrome after CT-guided, percutaneous T2 ethanol ablation for hyperhidrosis. Cardiovasc Intervent Radiol 2016;39(12):1785-8. PMID 27558116
19: Cantrell C, Reid C, Walker CS, Tidd SJS, Zhang R, Wilson R. Post-COVID postural orthostatic tachycardia syndrome (POTS): a new phenomenon. Front Neurol 2024;15:1297964. PMID 38585346
20: Chen L, Wang L, Sun J, et al. Midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syndrome. Circ J 2011;75(4):927-31. PMID 21301135
21: Coffin ST, Black BK, Biaggioni I, et al. Desmopressin acutely decreases tachycardia and improves symptoms in the postural tachycardia syndrome. Heart Rhythm 2012;9(9):1484-90. PMID 22561596
22: Cooperrider J, Kriegler J, Yunus S, Wilson R. A survey-based study examining differences in perception of postural orthostatic tachycardia syndrome between patients and primary care physicians. Cureus 2022;14(10):e30167. PMID 36238418
23: Corkal JC, Kimpinski K. A prospective study of excessive postural heart rate change on head-up tilt. Clin Auton Res 2014;24(6):253-8. PMID 25270997
24: Davido B, Seang S, Barizien N, Tubiana R, de Truchis P. 'Post-COVID-19 chronic symptoms' - author's reply. Clin Microbiol Infect 2020:S1198-743X(20)30528-0. PMID 32898714
25: de Carvalho JF, de Oliveira CB, Boas RV, Matias MF, Bastos LM. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) with postural orthostatic tachycardia syndrome after silicone breast implantation: case report. Eur J Rheumatol 2023;10(1):23-5. PMID 35156619
26: Delle Donne G, Rosés Noguer F, Till J, Salukhe T, Prasad SK, Daubeney PEF. Ivabradine in postural orthostatic tachycardia syndrome: preliminary experience in children. Am J Cardiovasc Drugs 2018;18(1):59-63. PMID 29027608
27: Diekman S, Chung T. Post-acute sequelae of SARS-CoV-2 syndrome presenting as postural orthostatic tachycardia syndrome. Clin Exp Emerg Med 2023;10(1):18-25. PMID 36718484
28: Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev 2004;56:331-49. PMID 15317907
29: El Sayed H, Hainsworth R. Salt supplementation increases plasma volume and orthostatic tolerance in patients with unexplained syncope. Heart 1996;75:134-40. PMID 8673750
30: Eslami M, Mollazadeh R, Mirshafiee S, et al. Postural orthostatic tachycardia syndrome and orthostatic hypotension post COVID-19. Infect Disord Drug Targets 2023;23(1):e100622205846. PMID 35692134
31: Fedorowski A. Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management. J Intern Med 2019;285(4):352-66. PMID 30372565
32: Fedorowski A, Sutton R. Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome. Nat Rev Cardiol 2023;20(5):281-2. PMID 36732397
33: Figueroa RA, Arnold AC, Nwazue VC, et al. Acute volume loading and exercise capacity in postural tachycardia syndrome. J Appl Physiol (1985) 2014;117(6):663-8. PMID 25059240
34: Fisher CJ, Katzan I, Heinberg LJ, Schuster AT, Thompson NR, Wilson R. Psychological correlates of patients with postural orthostatic tachycardia syndrome (POTS). Auton Neurosci 2020;227:102690. PMID 32544859
35: Fouad FM, Tadena-Thome L, Bravo EL, Tarazi RC. Idiopathic hypovolemia. Ann Intern Med 1986;104:298-303. PMID 3511818
36: Freeman R, Lirofonis V, Farquhar WB, Risk M. Limb venous compliance in patients with idiopathic orthostatic intolerance and postural tachycardia. J Appl Physiol 2002;93:636-44. PMID 12133874
37: Freitas J, Santos R, Azevedo E, Costa O, Carvalho M, de Freitas AF. Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone. Clin Auton Res 2000;10:293-9. PMID 11198485
38: Frye WS, King CK, Schaefer MR, Decker J, Kuhn B. "You Look Perfectly Healthy to Me": living with postural orthostatic tachycardia syndrome through adolescents' and parents' Eyes. Clin Pediatr (Phila) 2023;62(6):622-32. PMID 36475313
39: Fu Q, Vangundy TB, Galbreath MM, et al. Cardiac origins of the postural orthostatic tachycardia syndrome. J Am Coll Cardiol 2010;55(25):2858-68. PMID 20579544
40: Fu Q, Vangundy TB, Shibata S, Auchus RJ, Williams GH, Levine BD. Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome. Hypertension 2011;58(2):167-75. PMID 21690484
41: Galbreath MM, Shibata S, VanGundy TB, Okazaki K, Fu Q, Levine BD. Effects of exercise training on arterial-cardiac baroreflex function in POTS. Clin Auton Res 2011;21(2):73-80. PMID 21103906
42: Gamboa A, Paranjape SY, Black BK, et al. Inspiratory resistance improves postural tachycardia: a randomized study. Circ Arrhythm Electrophysiol 2015;8(3):651-8. PMID 25792354
43: Garland EM, Raj SR, Black BK, Harris PA, Robertson D. The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome. Neurology 2007;69:790-8. PMID 17709712
44: Gee ME, Watkins AK, Brown JN, Young EJA. Ivabradine for the treatment of postural orthostatic tachycardia syndrome: a systematic review. Am J Cardiovasc Drugs 2018;18(3):195-204. PMID 29330767
45: Gómez-Moyano E, Rodríguez-Capitán J, Gaitán Román D, et al. Postural orthostatic tachycardia syndrome and other related dysautonomic disorders after SARS-CoV-2 infection and after COVID-19 messenger RNA vaccination. Front Neurol 2023;14:1221518. PMID 37654428
46: González-Alvarez F, Estañol B, González-Hermosillo JA, et al. Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome. J Hypertens 2024;42(5):928-32. PMID 38526146
47: Gordon VM, Opfer-Gehrking TL, Novak V, Low PA. Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome. Clin Auton Res 2000;10:29-33. PMID 10750641
48: Grigoriou E, Boris JR, Dormans JP. Postural orthostatic tachycardia syndrome (POTS): association with Ehlers-Danlos syndrome and orthopaedic considerations. Clin Orthop Relat Res 2015;473(2):722-8. PMID 25156902
49: Guller U, Turek J, Eubanks S, Delong ER, Oertli D, Feldman JM. Detecting pheochromocytoma: defining the most sensitive test. Ann Surg 2006;243:102-7. PMID 16371743
50: Gunning WT 3rd, Kvale H, Kramer PM, Karabin BL, Grubb BP. Postural orthostatic tachycardia syndrome is associated with elevated G-protein coupled receptor autoantibodies. J Am Heart Assoc 2019;8(18):e013602. PMID 31495251
51: Haensch CA, Lerch H, Schlemmer H, Jigalin A, Isenmann S. Cardiac neurotransmission imaging with 123I-meta-iodobenzylguanidine in postural tachycardia syndrome. J Neurol Neurosurg Psychiatry 2010;81(3):339-43. PMID 19687022
52: Haensch CA, Tosch M, Katona I, Weis J, Isenmann S. Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome. Muscle Nerve 2014;50(6):956-61. PMID 24647968
53: Hanson J, Richley M, Hsu JJ, Lin J, Afshar Y. Postural orthostatic tachycardia syndrome and orthostatic hypotension in post-acute sequelae of COVID-19 during pregnancy: a case report. Eur Heart J Case Rep 2022;6(12):ytac453. PMID 36518330
54: Hasan B, Almasri J, Marwa B, Klaas KM, Fischer PR. Treatment of postural orthostatic tachycardia syndrome with medication: a systematic review. J Child Neurol 2020;35(14):1004-16. PMID 32838632
55: Hermel M, Sweeney M, Abud E, et al. COVID-19 vaccination might induce postural orthostatic tachycardia syndrome: a case report. Vaccines (Basel) 2022;10(7):991. PMID 35891154
56: Hoeldtke RD, Bryner KD, Hoeldtke ME, Hobbs G. Treatment of postural tachycardia syndrome: a comparison of octreotide and midodrine. Clin Auton Res 2006;16:390-5. PMID 17036177
57: Hoeldtke RD, Davis KM. The orthostatic tachycardia syndrome: evaluation of autonomic function and treatment with octreotide and ergot alkaloids. J Clin Endocrinol Metab 1991;73:132-9. PMID 2045464
58: Huang RJ, Chun CL, Friday K, Triadafilopoulos G. Manometric abnormalities in the postural orthostatic tachycardia syndrome: a case series. Dig Dis Sci 2013;58(11):3207-11. PMID 24068608
59: Ives CT, Kimpinski K. Higher heart rate increments on head-up tilt in control subjects are not associated with autonomic dysfunction. Clin Neurophysiol 2014;125(10):2109-14. PMID 24613070
60: Jacob G, Biaggioni I. Idiopathic orthostatic intolerance and postural tachycardia syndromes. Am J Med Sci 1999;317:88-101. PMID 10037112
61: Jacob G, Costa F, Shannon JR, et al. The neuropathic postural tachycardia syndrome. N Engl J Med 2000;343:1008-14. PMID 11018167
62: Jacob G, Robertson D, Mosqueda-Garcia R, Ertl AC, Robertson RM, Biaggioni I. Hypovolemia in syncope and orthostatic intolerance role of the rennin-angiotensin syndrome. Am J Med 1997;103:128-33. PMID 9274896
63: Johansson M, Ståhlberg M, Runold M, et al. Long-haul post-COVID-19 symptoms presenting as a variant of postural orthostatic tachycardia syndrome: The Swedish Experience. JACC Case Rep 2021;3(4):573-80. PMID 33723532
64: Johnson JN, Mack KJ, Kuntz NL, Brands CK, Porter CJ, Fischer PR. Postural orthostatic tachycardia syndrome: a clinical review. Pediatr Neurol 2010;42(2):77-85. PMID 20117742
65: Jones PK, Shaw BH, Raj SR. Clinical challenges in the diagnosis and management of postural tachycardia syndrome. Pract Neurol 2016;16(6):431-8. PMID 27660311
66: Jordan J, Shannon JR, Diedrich A, Black BK, Robertson D. Increased sympathetic activation in idiopathic orthostatic intolerance: role of systemic adrenoreceptor sensitivity. Hypertension 2002;39:173-8. PMID 11799098
67: Kanjwal K, Jamal S, Kichloo A, Grubb BP. New-onset postural orthostatic tachycardia syndrome following coronavirus disease 2019 infection. J Innov Card Rhythm Manag 2020;11(11):4302-4. PMID 33262898
68: Kanjwal K, Karabin B, Kanjwal Y, Grubb BP. Autonomic dysfunction presenting as postural orthostatic tachycardia syndrome in patients with multiple sclerosis. Int J Med Sci 2010;7:62-7. PMID 20309394
69: Kanjwal K, Karabin B, Sheikh M, et al. Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. Pacing Clin Electrophysiol 2011;34(6):750-5. PMID 21410722
70: Kanjwal K, Saeed B, Karabin B, Kanjwal Y, Sheikh M, Grubb BP. Erythropoietin in the treatment of postural orthostatic tachycardia syndrome. Am J Ther 2012a;19(2):92-5. PMID 20838326
71: Kanjwal K, Saeed B, Karabin B, Kanjwal Y, Grubb BP. Use of methylphenidate in the treatment of patients suffering from refractory postural tachycardia syndrome. Am J Ther 2012b;19(1):2-6. PMID 20460983
72: Khan G, Giacona J, Mirfakhraee S, Vernino S, Vongpatanasin W. MEN2B masquerading as postural orthostatic tachycardia syndrome. JACC Case Rep 2022;4(13):814-8. PMID 35818599
73: Khurana RK. Experimental induction of panic-like symptoms in patients with postural tachycardia syndrome. Clin Auton Res 2006;16:371-7. PMID 16915526
74: Khurana RK, Eisenberg L. Orthostatic and non-orthostatic headache in postural tachycardia syndrome. Cephalalgia 2011;31(4):409-15. PMID 20819844
75: Kimpinski K, Figueroa JJ, Singer W, et al. A prospective, 1-year follow-up study of postural tachycardia syndrome. Mayo Clin Proc 2012;87(8):746-52. PMID 22795533
76: Kitsou V, Blomberg B, Lunde T, Saeed S. Intermittent left bundle branch block with septal flash and postural orthostatic tachycardia syndrome in a young woman with long COVID-19. BMJ Case Rep 2022;15(6):e249608. PMID 35672052
77: Kohn A, Chang C. The relationship between hypermobile Ehlers-Danlos syndrome (hEDS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). Clin Rev Allergy Immunol 2020;58(3):273-97. PMID 31267471
78: Kwan AC, Ebinger JE, Wei J, et al. Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 infection. Nat Cardiovasc Res 2022;1(12):1187-94. PMID 37303827
79: Lenders JW, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: which test is best. JAMA 2002;287;1427-34. PMID 11903030
80: Levine BD, Zuckerman JH, Pawelczyk JA. Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance. Circulation 1997;96(2):517-25. PMID 9244220
81: Li J, Zhang Q, Liao Y, Zhang C, Hao H, Du J. The value of acetylcholine receptor antibody in children with postural tachycardia syndrome. Pediatr Cardiol 2015;36(1):165-70. PMID 25087056
82: Loavenbruck A, Iturrino J, Singer W, et al. Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome. Neurogastroenterol Motil 2015;27(1):92-8. PMID 25483980
83: Maharaj N, Swarath S, Seecheran R, Seecheran V, Panday A, Seecheran N. Suspected COVID-19 mRNA vaccine-induced postural orthostatic tachycardia syndrome. Cureus 2023;15(1):e34236. PMID 36852364
84: Mallick D, Goyal L, Chourasia P, Zapata MR, Yashi K, Surani S. COVID-19 Induced Postural Orthostatic Tachycardia Syndrome (POTS): A Review. Cureus. 2023;15(3):e36955. PMID 37009342
85: Manger WM, Eisenhofer G. Pheochromocytoma diagnosis and management update. Curr Hypertens Rep 2004;6:477-84. PMID 15527694
86: Mannan H, Pain CM. Sex adjusted standardized prevalence ratios for celiac disease and other autoimmune diseases in patients with postural orthostatic tachycardia syndrome (POTS): a systematic review and meta-analysis. Heliyon 2023;9(2):e12982. PMID 36816268
87: Mathias CJ, Low DA, Iodice V, Owens AP, Kirbis M, Grahame R. Postural tachycardia syndrome--current experience and concepts. Nat Rev Neurol 2011;8(1):22-34. PMID 22143364
88: McDonald C, Frith J, Newton JL. Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. Europace 2011;13(3):427-30. PMID 21062792
89: Medow MS, Guber K, Chokshi S, Terilli C, Visintainer P, Stewart JM. The benefits of oral rehydration on orthostatic intolerance in children with postural tachycardia syndrome. J Pediatr 2019;214:96-102. PMID 31405524
90: Medow MS, Stewart JM. The postural tachycardia syndrome. Cardiol Rev 2007;15:67-75. PMID 17303993
91: Miglis MG, Goodman BP, Chémali KR, Stiles L. Re: 'Post-COVID-19 chronic symptoms' by Davido et al. Clin Microbiol Infect 2020b:S1198-743X(20)30511-5. PMID 32891765
92: Miglis MG, Prieto T, Shaik R, Muppidi S, Sinn DI, Jaradeh S. A case report of postural tachycardia syndrome after COVID-19. Clin Auton Res 2020a;30(5):449-51. PMID 32880754
93: Minhas R, Bharadwaj AS. COVID-19-Induced Postural Orthostatic Tachycardia Syndrome and Dysautonomia. Cureus. 2023;15(6):e40235. PMID: 37435242
94: Mokri B, Low PA. Orthostatic headaches without CSF leak in postural tachycardia syndrome. Neurology 2003;61:980-2. PMID 14557573
95: Moon J, Kim DY, Byun JI, et al. Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome. Health Qual Life Outcomes 2016;14(1):144. PMID 27729043
96: Morgan K, Chojenta C, Tavener M, Smith A, Loxton D. Postural orthostatic tachycardia syndrome during pregnancy: a systematic review of the literature. Auton Neurosci 2018;215:106-18. PMID 29784553
97: Mueller BR, Ray C, Benitez A, Robinson-Papp J. Reduced cardiovagal baroreflex sensitivity is associated with postural orthostatic tachycardia syndrome (POTS) and pain chronification in patients with headache. Front Hum Neurosci 2023;17:1068410. PMID 36992793
98: Mueller BR, Robinson-Papp J. Postural orthostatic tachycardia syndrome and migraine: a narrative review. Headache 2022;62(7):792-800. PMID 35852052
99: Mustafa HI, Robertson D. Beyond postural tachycardia syndrome. J Neurol Neurosurg Psychiatry 2010;81(3):237-8. PMID 20185461
100: Nakatani Y, Mizumaki K, Nishida K, Inoue H. Atrioventricular node ablation and pacemaker implantation for recurrent syncope in a patient with postural tachycardia syndrome (POTS). J Cardiovasc Electrophysiol 2011;22(11):1284-7. PMID 21539639
101: Narasimhan B, Calambur A, Moras E, Wu L, Aronow W. Postural orthostatic tachycardia syndrome in COVID-19: a contemporary review of mechanisms, clinical course and management. Vasc Health Risk Manag 2023;19:303-16. PMID 37204997
102: Nardone M, Guzman J, Harvey PJ, Floras JS, Edgell H. Effect of a neck compression collar on cardiorespiratory and cerebrovascular function in postural orthostatic tachycardia syndrome (POTS). J Appl Physiol (1985) 2020;128(4):907-13. PMID 32163327
103: Novak V, Spies JM, Novak P, McPhee BR, Rummans TA, Low PA. Hypocapnia and cerebral hypoperfusion in orthostatic intolerance. Stroke 1998;29:1876-81. PMID 9731612
104: Ocher RA, Padilla E, Hsu JC, Taub PR. Clinical and laboratory improvement inhyperadrenergic postural orthostatic tachycardia syndrome (POTS) after COVID-19 infection. Case Rep Cardiol 2021;2021:7809231. PMID 34471549
105: Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci (Lond) 2012;122(5):227-38. PMID 21919887
106: Ojha A, McNeeley K, Heller E, Alshekhlee A, Chelimsky G, Chelimsky TC. Orthostatic syndromes differ in syncope frequency. Am J Med 2010;123(3):245-9. PMID 20193833
107: Okamoto LE, Raj SR, Gamboa A, et al. Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity. Am J Physiol Heart Circ Physiol 2015;309(12):H2098-107. PMID 26453329
108: Okamoto LE, Raj SR, Peltier A, Gamboa A, et al. Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes. Clin Sci (Lond) 2012;122(4):183-92. PMID 21906029
109: Olshansky B, Cannom D, Fedorowski A, et al. Postural orthostatic tachycardia syndrome (POTS): a critical assessment. Prog Cardiovasc Dis 2020;63(3):263-70. PMID 32222376
110: O'Sullivan JS, Lyne A, Vaughan CJ. COVID-19-induced postural orthostatic tachycardia syndrome treated with ivabradine. BMJ Case Rep 2021;14(6):e243585. PMID 34127505
111: Owens MR, Kaur D. The neuromuscular evaluation of postural orthostatic tachycardia syndrome. Muscle Nerve 2023;68(5):714-7. PMID 37638416
112: Park KJ, Singer W, Sletten DM, Low PA, Bharucha AE. Gastric emptying inpostural tachycardia syndrome: a preliminary report. Clin Auton Res 2013;23(4):163-7. PMID 23708963
113: Parsaik A, Allison TG, Singer W, et al. Deconditioning in patients with orthostatic intolerance. Neurology 2012;79(14):1435-9. PMID 22993288
114: Peebles KC, Jacobs C, Makaroff L, Pacey V. The use and effectiveness of exercise for managing postural orthostatic tachycardia syndrome in young adults with joint hypermobility and related conditions: A scoping review. Auton Neurosci 2024;252:103156. PMID 38401460
115: Petelin Gadze Z, Bujan Kovac A, Adamec I, Milekic N, Sulentic V. Vagal nerve stimulation is beneficial in postural orthostatic tachycardia syndrome and epilepsy. Seizure 2018;57:11-3. PMID 29529557
116: Pianosi PT, Schroeder DR, Fischer PR. Cardiac responses to exercise distinguish postural orthostatic tachycardia syndrome variants. Physiol Rep 2016;4(22):pii: e13040. PMID 27884959
117: Piovesan EJ, Sobreira CF, Scola RH, et al. Episodic migraine associated with postural orthostatic tachycardia syndrome and vasovagal syncope: migraine triggers neuromediated syncope. Arq Neuropsiquiatr 2008;66:77-9. PMID 18392420
118: Plash WB, Diedrich A, Biaggioni I, et al. Diagnosing postural tachycardia syndrome: comparison of tilt testing compared with standing haemodynamics. Clin Sci (Lond) 2013;124(2):109-14. PMID 22931296
119: Posey JE, Martinez R, Lankford JE, Lupski JR, Numan MT, Butler IJ. Dominant transmission observed in adolescents and families with orthostatic intolerance. Pediatr Neurol 2017;66:53-8.e5. PMID 27773421
120: Raj SR. The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & management. Indian Pacing Electrophysiol J 2006;6:84-99. PMID 16943900
121: Raj SR, Biaggioni I, Yamhure PC, et al. Renin-aldosterone paradox and perturbed blood volume regulation underlying postural tachycardia syndrome. Circulation 2005a;111:1574-82. PMID 15781744
122: Raj SR, Black BK, Biaggioni I, et al. Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Circulation 2009a;120(9):725-34. PMID 19687359
123: Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation 2005b;111:2734-40. PMID 15911704
124: Raj SR, Dzurik MV, Biaggioni I, et al. Diagnosing postural tachycardia syndrome: comparison of tilt versus standing. Circulation 2005c;112:U765.
125: Raj SR, Guzman JC, Harvey P, et al. Canadian cardiovascular society position statement on postural orthostatic tachycardia syndrome (POTS) and related disorders of chronic orthostatic intolerance. Can J Cardiol 2020;36(3):357-72. PMID 32145864
126: Raj SR, Robertson D. Blood volume perturbations in the postural tachycardia syndrome. Am J Med Sci 2007;334:57-60. PMID 17630594
127: Raj V, Harnan KL, Raj SR, et al. Psychiatric profile and attention deficits in postural tachycardia syndrome. J Neurol Neurosurg Psychiatry 2009b;80:339-44. PMID 18977825
128: Rattray C. Idiopathic osteoporosis, Ehlers-Danlos syndrome, postural orthostatic tachycardia syndrome, and mast cell activation disorder in a 27-year-old male patient: a unique case presentation. Clin Case Rep 2022;10(5):e05887. PMID 35600027
129: Razumovsky AY, DeBusk K, Calkins H, et al. Cerebral and systemic hemodynamics changes during upright tile in chronic fatigue syndrome. J Neuroimaging 2003;13:57-67. PMID 12593133
130: Reddy S, Reddy S, Arora M. A case of postural orthostatic tachycardia syndrome secondary to the messenger RNA COVID-19 vaccine. Cureus 2021;13(5):e14837. PMID 33968543
131: Reynolds GK, Lewis DP, Richardson AM, Lidbury BA. Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort. J Intern Med 2014;275(4):409-17. PMID 24206536
132: Rigo S, Urechie V, Diedrich A, Okamoto LE, Biaggioni I, Shibao CA. Impaired parasympathetic function in long-COVID postural orthostatic tachycardia syndrome - a case-control study. Bioelectron Med 2023;9(1):19. PMID 37670400
133: Robertson D. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci 1999;317(2):75-7. PMID 10037110
134: Robertson D, Flattem N, Tellioglu T, et al. Familial orthostatic tachycardia due to norepinephrine transporter deficiency. Ann N Y Acad Sci 2001;940:527-43. PMID 11458707
135: Roerink ME, Lenders JW, Schmits IC, et al. Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome. J Intern Med 2017;281(2):179-88. PMID 27696568
136: Roma M, Marden CL, De Wandele I, Francomano CA, Rowe PC. Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome. Auton Neurosci 2018;215:89-96. PMID 29519641
137: Ross AJ, Ocon AJ, Medow MS, Stewart JM. A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome. Clin Sci (Lond) 2014;126(4):289-96. PMID 23978222
138: Rubin R. Large cohort study finds possible association between postural orthostatic tachycardia syndrome and COVID-19 vaccination but far stronger link with SARS-CoV-2 infection. JAMA 2023;329(6):454-6. PMID 36696120
139: Sanada Y, Azuma J, Hirano Y, Hasegawa Y, Yamamoto T. Overlapping myocarditis and postural orthostatic tachycardia syndrome after COVID-19 messenger RNA vaccination: a case report. Cureus 2022;14(11):e31006. PMID 36475233
140: Sandroni P, Opfer-Gehrking TL, Singer W, Low PA. Pyridostigmine for treatment of neurogenic orthostatic hypotension: a follow-up survey study. Clin Auton Res 2005;15:51-3. PMID 15768203
141: Schondorf R. Acetylcholinesterase inhibition in the treatment of hypotension. J Neurol Neurosurg Psychiatry 2003;74:1187. PMID 12933916
142: Schondorf R, Benoit J, Stein R. Cerebral autoregulation is preserved in postural tachycardia syndrome. J Appl Physiol 2005;99:828-35. PMID 15860686
143: Schondorf R, Low PA. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia. Neurology 1993;43:132-7. PMID 8423877
144: Schroeder C, Tank J, Boschmann M, et al. Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance. Circulation 2002;105:347-53. PMID 11804991
145: Seeley MC, Gallagher C, Ong E, et al. Poor health-related quality of life in postural orthostatic tachycardia syndrome in comparison with a sex- and age-matched normative population. Clin Auton Res 2023;33(4):469-77. PMID 37338634
146: Shannon JR, Flattem NL, Jordan J, et al. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med 2000;342:541-9. PMID 10684912
147: Shibao C, Arzubiaga C, Roberts, LJ, et al. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension 2005;45:385-90. PMID 15710782
148: Singer W, Opfer-Gehrking TL, McPhee BR, Hilz MJ, Bharucha AE, Low PA. Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. J Neurol Neursurg Psychiatry 2003;74:1294-8. PMID 12933939
149: Singer W, Sandroni P, Opfer-Gerhking TL, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 2006;63:513-8. PMID 16476804
150: Singer W, Sletten DM, Opfer-Gehrking TL, Brands CK, Fischer PR, Low PA. Postural tachycardia in children and adolescents: what is abnormal. J Pediatr 2012;160(2):222-6. PMID 21996154
151: Singer W, Spies JM, McArthur J, et al. Prospective evaluation of somatic and autonomic small fibers in selected autonomic neuropathies. Neurology 2004;62:612-8. PMID 14981179
152: Sousa A, Lebreiro A, Freitas J, Maciel MJ. Long-term follow-up of patients with postural tachycardia syndrome. Clin Auton Res 2012;22(3):151-3. PMID 22190289
153: Staud R. Autonomic dysfunction in fibromyalgia syndrome: postural orthostatic tachycardia. Curr Rheumatol Rep 2008;10:463-6. PMID 19007537
154: Stewart JM. Pooling in chronic orthostatic intolerance: arterial vasoconstrictive but not venous compliance defects. Circulation 2002;105:2274-81. PMID 12010910
155: Stewart JM. Microvascular filtration is increased in postural tachycardia syndrome. Circulation 2003;107:2816-22. PMID 12756156
156: Stewart JM, Del Pozzi AT, Pandey A, Messer ZR, Terilli C, Medow MS. Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt. Hypertension 2015;65(3):636-43. PMID 25510829
157: Stewart JM, Munoz J, Weldon A. Clinical and physiological effects of an acute alpha-1 adrenergic agonist and a beta-1 adrenergic antagonist in chronic orthostatic intolerance. Circulation 2002;106:2946-54. PMID 12460877
158: Stewart JM, Weldon A. Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome. J Appl Physiol 2000;89:1505-12. PMID 11007589
159: Stewart JM, Weldon A. Reflex vascular defects in the orthostatic tachycardia syndrome of adolescents. J Appl Physiol 2001;90:2025-32. PMID 11356761
160: Streeten DH. Pathogenesis of hyperadrenergic orthostatic hypotension: evidence of disordered venous innervation exclusively in the lower limbs. J Clin Invest 1990;86:1582-8. PMID 2243132
161: Streeten DH, Scullard TF. Excessive gravitational blood pooling caused by impaired venous tone in the predominant non-cardiac mechanism of orthostatic intolerance. Clin Sci (Colch) 1996;90:277-85. PMID 8777834
162: Streeten DH, Thomas D, Bell DS. The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome. Am J Med Sci 2000;320:1-8. PMID 10910366
163: Sunami Y, Sugaya K, Miyakoshi N, Iwazaki O, Takahashi K. Association of autoantibodies to muscarinic acetylcholine receptors with gastrointestinal symptoms and disease severity in patients with postural orthostatic tachycardia syndrome. Immunol Res 2022;70(2):197-207. PMID 34993884
164: Tank J, Schroeder C, Diedrich A, et al. Selective impairment in sympathetic vasomotor control with norepinephrine transporter inhibition. Circulation 2003;107:2949-54. PMID 12796139
165: Tanking C, Lakkananurak C, Srisakvarakul C, Jitpreeda A, Threechod K, Sukitpunyaroj D. Postural orthostatic tachycardia syndrome and other autonomic dysfunctions following COVID-19: incidence, characteristics, and associated factors. J Arrhythm 2024;40(2):230-6. PMID 38586859
166: Taub PR, Zadourian A, Lo HC, Ormiston CK, Golshan S, Hsu JC. Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome. J Am Coll Cardiol 2021;77(7):861-71. PMID 33602468
167: Thanavaro JL, Thanavaro KL. Postural orthostatic tachycardia syndrome: diagnosis and treatment. Heart Lung 2011;40(6):554-60. PMID 21329983
168: Thieben MJ, Sandroni P, Sletten DM, et al. Postural orthostatic tachycardia syndrome: the Mayo Clinic experience. Mayo Clin Proc 2007;82:308-13. PMID 17352367
169: Tufvesson H, Hamrefors V, Fedorowski A, Hansson M, Ohlsson B. Gastrointestinal symptoms in patients with postural orthostatic tachycardia syndrome in relation to hemodynamic findings and immunological factors. Front Physiol 2024;15:1342351. PMID 38348221
170: Unger N, Pitt C, Schmidt IL, et al. Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. Eur J Endocrinol. 2006;154:409-17. PMID 16498054
171: Vasavada AM, Verma D, Sheggari V, et al. Choices and challenges with drug therapy in postural orthostatic tachycardia syndrome: a systematic review. Cureus 2023;15(5):e38887. PMID 37313107
172: Vernino S, Bourne KM, Stiles LE, Grubb BP, et al. Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1. Auton Neurosci 2021;235:102828. PMID 34144933
173: Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune neuropathies. N Engl J Med 2000;343:847-55. PMID 10995864
174: Vincent S, Bieck PR, Garland EM, et al. Clinical assessment of norepinephrine transporter blockage through biochemical and pharmacological profiles. Circulation 2004;109:3202-7. PMID 15184278
175: Wafa SE, Chahal CA, Sawatari H, et al. Frequency of arrhythmias and postural orthostatic tachycardia syndrome in patients with Marfan syndrome: a nationwide inpatient study. J Am Heart Assoc 2022;11(17):e024939. PMID 36000435
176: Wallman D, Weinberg J, Hohler AD. Ehlers-Danlos syndrome and postural tachycardia syndrome: a relationship study. J Neurol Sci 2014;340(1-2):99-102. PMID 24685354
177: Williams EL, Raj SR, Schondorf R, Shen WK, Wieling W, Claydon VE. Salt supplementation in the management of orthostatic intolerance: vasovagal syncope and postural orthostatic tachycardia syndrome. Auton Neurosci 2022;237:102906. PMID 34823150
178: Winker R, Barth A, Bidmon D, et al. Endurance exercise training in orthostatic intolerance: a randomized, controlled trial. Hypertension 2005;45:391-8. PMID 15699447
179: Yozgat Y, Temur HO, Coban S, et al. Short-term efficacy of ORS formulation and propranolol regimen in children with POTS. Arch Pediatr 2020;27(6):328-32. PMID 32651146
180: Zhang Q, Chen X, Li J, Du J. Orthostatic plasma norepinephrine level as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome. J Transl Med 2014;12:249. PMID 25204388
181: Zhang Q, Liao Y, Tang C, Du J, Jin H. Twenty-four-hour urinary sodium excretion and postural orthostatic tachycardia syndrome. J Pediatr 2012;161(2):281-4. PMID 22424949
182: Zhang R, Mayuga K, Shields R, Cantrell C, Wilson R. Skin biopsy and quantitative sudomotor axon reflex testing in patients with postural orthostatic tachycardia syndrome. Cureus 2022;14(11):e31021. PMID 36349067
183: Zhao J, Tang C, Jin H, Du J. Plasma copeptin and therapeutic effectiveness of midodrine hydrochloride on postural tachycardia syndrome in children. J Pediatr 2014;165(2):290-4.e1. PMID 24857518
184: Zhao S, Tran VH. Postural orthostatic tachycardia syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024. PMID 31082118
185: Zhou W, Zikos TA, Clarke JO, Nguyen LA, Triadafilopoulos G, Neshatian L. Regional gastrointestinal transit and contractility patterns vary in postural orthostatic tachycardia syndrome (POTS). Dig Dis Sci 2021;66(12):4406-13. PMID 33428036

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Postural orthostatic tachycardia syndrome

Differential Diagnosis

postural symptoms without tachycardia
orthostatic tachycardia without symptoms
those with orthostatic tachycardia but another overt cause for excessive tachycardia
anemia
anxiety
- bleeding
- chronic fatigue syndrome
- deconditioning
- dehydration
- disequilibrium
- dizziness
- hyperthyroidism
- hyperventilation syndrome
- hypotension
- medication-induced autonomic dysregulation
- mitral valve prolapse syndrome
- neurally mediated presyncope or syncope
- orthostatic hypotension
- panic disorder
- pheochromocytoma
- presyncope
- prolonged bed rest
- symptomatic secondary orthostatic tachycardia
- syncope

Also Relevant

Acute autonomic neuropathies
Acute pandysautonomia
Autonomic neuropathy: treatment
Chronic autonomic neuropathies
Dizziness

Clinical Categories

Patient Handouts

Web References

Guidelines

AAN: Clinical Autonomic Testing Assessment

Clinical Trials

NIH: POTS

Postural orthostatic tachycardia syndrome (POTS) …

Postural orthostatic tachycardia syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Symptoms of Postural Orthostatic Tachycardia Syndrome (Particularly When Upright)

Table 2. Diagnostic Criteria for Postural Orthostatic Tachycardia Syndrome

Prognosis and complications

Biological basis

Anatomic localization

Pathophysiology

Table 3. Conditions Associated with Postural Orthostatic Tachycardia

Epidemiology

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Media

References

Contributors

Author

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Familial dysautonomia

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Common maculopathies

Peripheral nerve complications of HIV-1 infection

Toxic and nutritional deficiency optic neuropathies

Postural orthostatic tachycardia syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Symptoms of Postural Orthostatic Tachycardia Syndrome (Particularly When Upright)

Table 2. Diagnostic Criteria for Postural Orthostatic Tachycardia Syndrome

Prognosis and complications

Biological basis

Anatomic localization

Pathophysiology

Table 3. Conditions Associated with Postural Orthostatic Tachycardia

Epidemiology

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Media

References

Contributors

Author

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Familial dysautonomia

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Common maculopathies

Peripheral nerve complications of HIV-1 infection

Toxic and nutritional deficiency optic neuropathies

This is an article preview.
Start a Free Account
to access the full version.