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Postural tachycardia syndrome

Postural tachycardia syndrome
Literature review current through: Jan 2024.
This topic last updated: Feb 14, 2023.

INTRODUCTION AND TERMINOLOGY — Postural tachycardia syndrome (POTS) is a disorder characterized by orthostatic intolerance. Orthostatic intolerance describes an abnormal autonomic response causing symptoms that develop while sustaining an upright posture. Orthostatic intolerance symptoms include lightheadedness, dizziness, blurring or fading of vision, generalized weakness, fatigue, palpitations, mental clouding, anxiety, nausea, dyspnea, or headache. Disorders characterized by orthostatic intolerance include (figure 1 and table 1):

Postural tachycardia syndrome – The clinical syndrome of POTS includes intermittent symptoms of orthostatic intolerance accompanied by excessive tachycardia without arterial hypotension. POTS is also called "postural orthostatic tachycardia syndrome," but the word "orthostatic" may be omitted. POTS has previously been described as neurocirculatory asthenia, mitral valve prolapse syndrome, hyperdynamic beta adrenergic state, irritable heart, soldier's heart, Da Costa syndrome, and irritable heart syndrome [1].

Orthostatic hypotension – This disorder is defined by a sustained reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of 10 mmHg, with or without symptoms during the assessment, within three minutes of standing or head-up tilt [2]. Orthostatic hypotension is discussed in detail separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".)

Reflex syncope (also called vasovagal syncope, neurally mediated syncope, or neurocardiogenic syncope) – Symptoms include a distinct prodrome of facial pallor, sweating, nausea, yawning, or hyperventilation culminating in a transient loss of consciousness and postural tone [2,3]. Reflex syncope often occurs during prolonged standing and may coexist with POTS. In a study of 300 patients with POTS, 18 (6 percent) also had syncope during tilt-table testing [4]. Reflex syncope is discussed in detail separately. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)

Chronic isolated orthostatic intolerance – Chronic symptoms of orthostatic intolerance may occur in patients without excessive tachycardia [5]. This condition of chronic orthostatic intolerance is often considered to be on the POTS spectrum broadly interpreted, as patients may have a modest elevation in heart rate.

This topic discusses POTS. Other conditions characterized by orthostatic intolerance are discussed separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Treatment of orthostatic and postprandial hypotension" and "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation" and "Reflex syncope in adults and adolescents: Treatment".)

PATHOPHYSIOLOGY

Normal orthostatic response — The ability to stand erect against the force of gravity requires sufficient muscular strength, a firm skeletal frame, a sense of balance, consciousness, and modulation of cardiovascular autonomic function to compensate for the downward displacement of 500 to 800 mL of blood to the abdomen and lower extremities [3,6].

The autonomic nervous system responds to the unloading of carotid sinus and aortic arch baroreceptors during standing by increasing cardiovascular sympathetic adrenergic outflow and decreasing cardiovagal parasympathetic outflow [7]. The sympathetic response increases peripheral vasoconstrictor tone, cardiac rate, and inotropic state. The parasympathetic response is withdrawal of vagal tone from the heart, which increases heart rate [8]. Also important for orthostatic tolerance is the skeletal "muscle pump," whereby rhythmic contraction of lower extremity and abdominal muscles squeezes capacitance vessels and assists the return of venous blood to the heart [9]. These combined responses maintain cardiac output for perfusion of the brain and other organs.

Mechanisms — In POTS, a variety of pathophysiologic conditions may lead to a final common pathway of orthostatic intolerance with tachycardia. More than one mechanism may be present in a given patient. Potential underlying causes include:

Hypovolemia and deconditioning – In the majority of POTS patients, intravascular volume is reduced; this contributes to decreased venous return to the heart, reflex tachycardia, and orthostatic intolerance [10,11]. A deconditioned state further contributes to hypovolemic symptoms because a higher heart rate is needed to sustain cardiac output.

POTS is associated with low blood volume [12], decreased cardiac left-ventricular mass [13], and reduced cardiac stroke volume [14], a pattern remarkably similar to that in people who are highly deconditioned or who have been at prolonged bed rest [15]. As an example, in one study, healthy volunteers placed at sustained bed rest for two weeks developed orthostatic intolerance along with a 17 percent reduction in plasma volume and a 5 percent reduction in cardiac mass [16].

Many patients with POTS avoid physical activity because of symptoms of orthostatic intolerance, exacerbating a deconditioned state that may further contribute to hypovolemic symptoms. Reconditioning efforts often improve but do not fully restore function or eliminate symptoms in POTS, suggesting that additional factors are present [17]. Among them, somatic hypervigilance, in which patients perceive mild or routine sensory information as intense or distressing, can sustain a deconditioned state [15].

Neuroendocrine dysfunction – Some patients with POTS have evidence of increased cardiovascular adrenergic function separate from tachycardia, suggesting that POTS represents a hyperadrenergic state. Such patients have an increased blood pressure overshoot during the Valsalva maneuver [18]. On average, patients with POTS have higher catecholamine levels than healthy controls [19], and some have been found to have an increase in norepinephrine on standing [20].

Some patients with POTS have a functional or acquired deficiency in the norepinephrine transporter membrane protein. In these patients, increased synaptic norepinephrine leads to excessive adrenergic responses to physiologic stimuli [21].

Studies have found that patients with POTS have on average lower levels of plasma renin and aldosterone [10,22] and higher levels of plasma angiotensin II [23]; these findings are in contrast with what is expected in patients with hypovolemia and suggest angiotensin II receptor subtype imbalance as a potential theory for POTS [24]. Correspondingly, higher levels of angiotensin II may reflect deficiency in the vasodilatory effects of endothelial nitric oxide also found in some POTS patients [8,22,25,26].

Neuropathy – A small-fiber neuropathy may be present in up to one-half of POTS cases and contributes to dysautonomia. Abnormalities in sudomotor testing were reported in 43 to 63 percent of POTS patients and were associated with gastrointestinal symptoms such as nausea, bloating, constipation, and abdominal pain [20,27-29]. In another study, POTS patients had reduced resting muscle sympathetic nerve activity and a delayed cardiovascular adrenergic response to hypotensive challenge suggesting impairment of adrenergic nerve function [30]. Additionally, some POTS patients have reduced intraepidermal nerve fiber density or small nerve fiber morphologic changes indicating selective impairment of autonomic fibers [29,31].

Autoimmunity – An autoimmune basis for a small number of POTS patients has been linked to the observation of orthostatic symptoms following a viral illness [32,33]. Additionally, autoantibodies to the ganglionic nicotinic acetylcholine receptor [20,34] and alpha-1 adrenergic, beta-1/2 adrenergic, and angiotensin II type 1 receptors [35-38] have been detected in a few patients. These autoantibodies are speculated to impair effective peripheral vasoconstriction leading to a compensatory tachycardia [36,38].

However, the presence of autoantibodies in POTS should be interpreted cautiously. Low antibody levels were reported in small numbers of cases, some without adequate controls or physiologic specificity, and the levels of antibodies did not correlate with the severity of POTS [20]. In one study, more than half of patients who reported onset of POTS following a viral illness also recalled a lifelong tendency toward orthostatic symptoms, suggesting the illness may have unmasked or exacerbated a preexisting subclinical diathesis [39].

Multiple case series have reported orthostatic intolerance or POTS as a delayed manifestation of COVID-19 infection in some patients who had no prior history of symptoms of orthostatic intolerance [40-45]. POTS and other orthostatic intolerance syndromes have also been reported following COVID-19 vaccination [46,47]. However, a large cohort study of more than 280,000 patients who received the COVID-19 vaccination and more than 12,000 who developed a COVID-19 infection found that the risk of POTS and related syndromes within 90 days of exposure was more than five-fold higher for those who developed infection than those who received vaccination (odds ratio 5.35, 95% CI 5.1-5.7) [48].

EPIDEMIOLOGY — Patients with POTS are typically young (between the ages of 15 and 50 years) and female (5:1 predominance of females to males) [49-51]. A large cross-sectional, community-based online survey of patients identified that half of patients first developed symptoms in adolescence, and more than 90 percent were white females of childbearing age [39].

Some low-quality data estimate the prevalence of POTS to be between 0.1 and 1 percent [52].

CLINICAL FEATURES — The hallmark symptoms of orthostatic intolerance in patients with POTS occur in the upright posture. Additionally, a number of less-specific nonorthostatic symptoms are common in POTS (table 2).

These symptoms are disabling in many patients. Patients with POTS experience impairments in quality of life across multiple domains of physical and social functioning. Short-Form Health Survey assessment of POTS patients found functional limitations comparable to those of patients with chronic obstructive pulmonary disease or congestive heart failure, conditions that generally affect patients older than those with POTS [53]. In one series of 94 patients with a mean age of 34 years, 25 percent were disabled and unable to work [53].

Orthostatic intolerance — Symptoms of orthostatic intolerance are brought on by standing and relieved by sitting down. They typically include lightheadedness, palpitations, fading vision, presyncope, difficulty concentrating, and headache. Some patients will also report dyspnea, chest pain, nausea, tremulousness, flushing, or blurred vision [39,54,55]. The orthostatic headache that may occur in POTS consists of dull occipital and cervical trapezius pain (so-called "coat hanger headache") while in the upright position and is relieved by sitting [54].

Orthostatic symptoms often vary by day, week, and month:

Orthostatic symptoms are more pronounced when standing still; walking is generally better tolerated. As examples, patients may be unable to stand in a checkout line at a store, in the kitchen long enough to prepare a meal, or in conversation at social gatherings without frequently taking steps or shifting weight to activate the skeletal muscle pump to improve venous return to the heart.

Orthostatic symptoms and heart rates are more pronounced during conditions of increased orthostatic stress or vasodilation. Prolonged recumbency can lead to deconditioning and exacerbation of symptoms.

Symptoms tend to be worse during early morning hours, in hot weather, during menses, and during febrile illness or stress. Patients with POTS are almost always unable to tolerate standing while taking a warm shower, and many must sit down to bathe. After a shower they may have to lie down and rest.

Patients may report exaggerated orthostatic symptoms from dehydration or medications that can lower blood pressure.

Symptoms unrelated to orthostasis — Many patients with POTS also report symptoms that are unrelated to postural changes. Symptoms may be intermittent or constant and include anxiety, fatigue, resting or nocturnal paroxysmal tachycardia, acrocyanosis, chest pain, nausea, bloating, constipation, diarrhea, abdominal pain, headaches, difficulty concentrating, syncope, blurred vision, dry mouth, dry eyes, foot coldness, extremity tingling, cutaneous flushing, or urinary frequency [39,55]. The extensive number and nonspecific nature of these symptoms makes attributing them to a diagnosis of POTS with certainty challenging. (See 'Diagnostic approach' below.)

Anxiety – Anxiety is common in POTS [56,57] but appears phenomenologically distinct from symptoms of generalized anxiety disorder or panic disorder [58,59]. It is characterized by somatic hypervigilance [53,60]. Psychological profiles of patients with POTS have found anxiety appears to be driven by heightened awareness of internal somatic sensations or fear conditioning in anticipation of orthostatic stress, rather than by trait anxiety or neurosis [59,61]. When patients were shown a series of randomly presented neutral, pleasant, or unpleasant images in the supine and upright postures, their emotional responsivity to unpleasant images was greater during head-up tilt, suggesting that increased autonomic reactivity amplified their sense of internal threat [61,62].

Measures of increased somatic vigilance, somatic anxiety, and catastrophic thinking correlate with functional disability in POTS [59,60,63].

Fatigue – Fatigue is a common symptom among patients with POTS but may be underrecognized, as reports identifying the association vary widely (21 to 93 percent) [20,39,64]. Fatigue may be attributable to orthostatic intolerance and/or exercise intolerance in POTS; however, in many patients, a sense of low energy does not always resolve upon sitting but persists at rest and may recur in cycles lasting for days or weeks at a time [55].

Cognitive dysfunction – Neuropsychological testing of patients with POTS has shown mild impairments in attention, cognitive processing speed, memory function, and executive function, even when in seated or supine positions [56]. Selective attention and cognitive processing speed, in particular, are reduced [65].

There is also consistent evidence of mild to moderate depression in POTS. These impairments do not correlate with heart rate changes but have been speculated to be due to high levels of circulating catecholamines or central norepinephrine dysregulation rather than decreased cerebral perfusion [65].

Gastrointestinal disturbances – Gastrointestinal complaints are common in POTS [66]. They may include nausea, irregular bowel movements, bloating, diarrhea, abdominal pain or cramping, constipation, heartburn, or vomiting [20,67,68]. Irritable bowel syndrome is diagnosed in 30 percent and gastroparesis in 14 percent [39,67]. Nausea and vomiting can also cause hypovolemia and exacerbate orthostatic intolerance symptoms.

The mechanism of gastrointestinal symptoms in POTS is not understood but is likely multifactorial. An investigation of splanchnic-mesenteric vasoregulation in 11 patients found an excessive splanchnic blood pooling in POTS patients compared with controls [69]. Intestinal hypomobility resulting from circulating catecholamines also likely plays a role [70].

Sleep disturbances – Nonrestorative sleep and daytime drowsiness are common and contribute to fatigue and impaired health-related quality of life [71,72].

Headache – Primary headache syndromes including migraine and tension-type headache are common, with prevalence estimates of 35 percent or higher [20,39,73,74]. Central sensitization has been proposed as a contributing factor [73].

Overactive bladder – In a small study of 19 females with POTS who completed a standardized questionnaire for overactive bladder symptoms, 13 met clinical criteria for overactive bladder, with nocturia being the most bothersome symptom, followed by frequency and urgency [75]. It is unclear whether symptoms are from autonomic dysregulation of lower urinary tract function or a consequence of recommending increased oral fluid intake, a common strategy for managing POTS.

Skin findings – Some patients with POTS may also have dermatologic manifestation including acrocyanosis, livedo reticularis, Raynaud phenomenon, and various rashes [76,77]. Bier anemic spots (white macules on erythematous background), cyanosis, and urticaria-like eruption (BASCULE) syndrome is a vasomotor dermatosis that has been associated with POTS in several case reports [78-81]. Symptoms are typically present in the lower legs, occur or worsen with standing, and may improve with treatment of POTS symptoms or antihistamines.

DIAGNOSTIC APPROACH

Diagnostic criteria — The diagnosis of POTS is made by:

History of symptoms of orthostatic intolerance with or without systemic symptoms

Correlation of symptoms with a sustained increase in upright heart rate by at least 30 beats/minute (40 beats/minute for patients under the age of 20 years) within 10 minutes of standing or head-up tilt, without orthostatic hypotension [2,54,82-84]

Autonomic testing to correlate symptoms with heart rate changes, confirm the diagnosis, and assess the degree of objective signs of orthostatic intolerance

Other diagnostic testing as needed to exclude alternative diagnoses or confounding concomitant conditions (see 'Differential diagnosis' below)

Clinical evaluation — The key physical finding is an excessive rise in resting heart rate within 10 minutes of standing, without decrease in blood pressure. Orthostatic intolerance symptoms should accompany tachycardia.

Symptomatic orthostatic tachycardia – In patients with POTS, the heart rate elevation should exceed 30 beats/minute (40 beats/minute in patients under 20 years of age) above a resting baseline while supine or seated.

Baseline heart rate and blood pressure should be measured after at least 5 minutes of rest supine and again after one minute of standing. If initial values are nondiagnostic, repeating the measurement of vital signs at 3, 5, or 10 minutes is often informative. The patient should be asked to stand quietly and still.

Pulse oximeter devices are useful for measuring orthostatic heart rates to display values much faster than the traditional method of counting the pulse over 15 seconds and multiplying by 4. The heart rate can vary greatly from moment to moment, so average rather than transient peak values should be recorded.

Patients with POTS should experience orthostatic intolerance symptoms during testing for orthostatic tachycardia. (See 'Orthostatic intolerance' above.)

A transient increase in heart rate during the first 20 seconds of standing is expected in healthy persons. In patients with POTS, heart rate increases at 30 to 60 seconds and may continue to gradually increase during standing. Additionally, an asymptomatic increase in heart rate by 30 or more beats/minute upon standing is common in healthy adolescents, and 5 percent may have a heart rate increase beyond 40 beats/minute. Because normative heart rate values are different for adolescents, an increase of at least 40 beats/minute is necessary for a diagnosis of POTS.

Postural elevations in heart rate without symptoms of orthostatic intolerance are insufficient to make the diagnosis of POTS [85-88]. In the absence of orthostatic symptoms, such an increase represents benign tachycardia [89]. In one study, the threshold of an increase in heart rate of 30 beats/minute at 10 minutes of standing was found to discriminate POTS from healthy controls with only 67 percent specificity [88].

In POTS, blood pressure during standing remains normal or may increase. By contrast, in orthostatic hypotension, there is a reduction of standing systolic or diastolic blood pressure by at least 20 or 10 mmHg, respectively.

In assessing the magnitude of heart rate changes for the diagnosis of POTS, current medications affecting heart rate, which may be impractical to hold in advance of an outpatient evaluation, should be taken into account. Beta blockers, for example, will suppress the rise in heart rate upon standing and could mask the change diagnostic of POTS. Adrenergic stimulants, norepinephrine transporter and reuptake inhibitors, anticholinergics, and beta-adrenoreceptor agonists can magnify the heart rate increase upon standing and lead to a false diagnosis of POTS [90].

Other findings – During a clinical examination, some patients may demonstrate subtle behaviors suggestive of orthostatic intolerance. While standing, patients may shift their weight back and forth; while sitting, they may entwine their legs [70].

Some POTS patients will demonstrate vasomotor changes during standing. Red or purple acrocyanosis, typically of the distal lower extremities, becomes evident during standing and may resolve when supine.

Neurologic examination is normal in POTS.

Autonomic testing — Autonomic testing is useful in the diagnosis of POTS in patients with orthostatic intolerance symptoms and for reassessment of changing symptoms over time. Autonomic testing is more sensitive and specific than random sampling of heart rate during clinical bedside assessment while standing [91].

Tilt-table testing – Vasomotor adrenergic autonomic testing using a tilt table provides objective evidence of orthostatic intolerance in patients with lightheadedness. It increases the diagnostic yield of assessing tachycardia in patients with POTS and helps exclude orthostatic hypotension. During passive head-up tilt-table testing, full activation of the leg muscles is not needed to support the weight of the body. Thus, it is possible to assess the hemodynamic response to the downward translocation of blood volume without the compensatory influence of the skeletal muscle pump, which may conceal objective signs of orthostatic intolerance during bedside assessment.

Testing should include noninvasive beat-to-beat measurement of both heart rate and blood pressure during tilt-table testing, which provides more precise information than does bedside examination [20,92]. Assessment should be based not on random or peak heart rates, but on time-averaged heart rates (from which normative values were derived) (figure 2) [20,85,92].

Sudomotor testing – Sudomotor testing should be performed as a routine component of formal autonomic testing, when available. Approximately half of POTS patients will have neuropathic abnormalities evident by sudomotor testing. Sudomotor deficits are typically postganglionic and patchy in distribution [20,27,29,83].

Laboratory testing — Laboratory tests are useful to exclude other or additional causes of orthostatic intolerance symptoms. Because orthostatic intolerance and systemic symptoms are not specific to POTS, we perform routine testing in the initial diagnostic evaluation of patients. This includes:

Plasma electrolytes

Complete blood count

Thyroid function testing

Electrocardiography

Additional testing may be considered depending on associated symptoms or history provided. Such testing may include:

Morning cortisol in the patient with hypotension to exclude adrenal insufficiency. (See "Measurement of cortisol in serum and saliva".)

Transthoracic echocardiography if heart pump failure is suspected. (See "Clinical manifestations and diagnosis of advanced heart failure", section on 'Echocardiography'.)

Supine and standing plasma catecholamines in patients with tachycardia and hypertension. Hyperadrenergic status is associated with an orthostatic increase in systolic blood pressure of at least 10 mmHg or plasma norepinephrine of at least 600 picograms/mL [19,55].

Twenty-four-hour urinary sodium excretion if hypovolemia is suspected. Values less than 100 mEq/24 hours suggest hypovolemia [20,93].

Gastric motility testing in the patient with early satiety or intractable nausea, particularly if the patient cannot maintain adequate oral fluid intake. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis", section on 'Assess gastric motility'.)

Tryptase in the patient with prominent flushing to screen for mast cell activation disorder (MCAD). (See "Mast cell disorders: An overview", section on 'Measure serum tryptase'.)

Serologic testing of autoantibodies has low specificity and is not routinely recommended in the evaluation of POTS.

DIFFERENTIAL DIAGNOSIS — Symptoms of orthostatic intolerance may indicate POTS or alternative orthostatic conditions. Other entities with symptoms that mimic some aspects of the orthostatic intolerance or nonorthostatic systemic symptoms seen in POTS such as lightheadedness, fatigue, or headaches may be excluded by distinguishing clinical features (table 1).

Alternative orthostatic conditions

Dehydration – A diagnosis of POTS should not be made in the patient who is acutely or chronically dehydrated from frequent diarrhea, vomiting, polyuria, or water deprivation. In these patients, the tachycardia may be secondary to intravascular hypovolemia with a reflex increase in heart rate to sustain cardiac output when preload is reduced. The typical hemodynamic profile of dehydration is orthostatic hypotension with compensatory tachycardia. Orthostatic hypotension is an exclusionary criterion for POTS.

Pharmacologic syndromes – A diagnosis of POTS should not be made before excluding tachycardia caused by medication that has the property of increasing the heart rate. Examples include sympathomimetics, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, atomoxetine, and anticholinergics, all of which vary in the degree to which they can influence heart rate in individual patients [90]. The clinician should also inquire about the use of caffeine, psychostimulants, weight loss pills, and decongestants, among others.

Orthostatic hypotension – Patients with orthostatic hypotension from volume depletion or medications frequently have postural tachycardia with hypotension on testing. Orthostatic hypotension is discussed in detail separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".)

Reflex syncope – Also called vasovagal, neurally mediated, or neurocardiogenic syncope, this condition is distinct from POTS in that it is an episodic phenomenon, whereas in POTS orthostatic symptoms occur to some degree on a continuous basis. In reflex syncope, bradycardia and hypotension may precede loss of postural tone and transient loss of consciousness.

However, the occurrence of syncope does not exclude POTS. Reflex syncope and POTS may coexist as distinct conditions in the same patient [19]. As an example, syncope may also occur in some patients with POTS during prolonged tilt-table testing [4,94]. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)

Chronic isolated orthostatic intolerance – Some patients may have orthostatic intolerance symptoms without accompanying tachycardia or with a normal heart rate increase [5]. Such patients do not meet diagnostic criteria for POTS and may be described as having chronic isolated orthostatic intolerance.

Chronic isolated orthostatic tachycardia – Patients found to have postural tachycardia without symptoms are not diagnosed as having POTS. An excessively elevated heart rate is typically defined as above the 95th percentile, meaning that 5 percent of the general population, including many asymptomatic individuals, may have an excessive rise in heart rate when standing (>30 beats/minute, >40 in adolescents) [89].

Inappropriate sinus tachycardia – The syndrome of inappropriate sinus tachycardia is defined by a fast sinus rhythm greater than 100 beats/minute at rest or 90 beats/minute averaged during 24 hours not due to identified underlying causes [95]. In contrast with POTS, the tachycardia occurs at rest rather than in response to the upright posture. Occasionally, inappropriate sinus tachycardia coexists with POTS. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia'.)

Other conditions

Panic and anxiety disorders – The somatic symptoms of POTS are phenomenologically distinct from symptoms in patients with primary psychiatric disorders (eg, panic disorder or anxiety disorder). Both present with palpitations, but panic attacks occur spontaneously, whereas the tachycardia in POTS is induced by the upright posture. Symptoms more strongly associated with panic attacks include a feeling of intense fear, a desire to flee, a sense of impending doom, a fear of losing control, a fear of "going crazy," or a fear of dying. (See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical Manifestations'.)

A large online survey of POTS patients found that 77 percent had initially been given a psychiatric diagnosis such as anxiety, panic disorder, or depression. However, once the diagnosis of POTS was made, only 37 percent continued to have a psychiatric diagnosis [39]. Assessment of POTS patients for psychiatric disorders by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria found that they did not have an increased prevalence of anxiety disorders or major depression as compared with the general population, but many had mild depressive symptoms [96].

While not commonly used in clinical practice, physiologic responses to drugs or other interventions can also differentiate a psychiatric disorder from the anxiety in POTS. Intravenous infusion of isoproterenol or sodium lactate, which precipitate panic in patients with panic disorder, did not produce typical symptoms in a series of patients with POTS, although these did cause palpitations, dyspnea, and trembling [58]. Another study compared tilt-table responses in patients with POTS with patients with panic disorder who were comparably tachycardic; the depth of respiration increased in POTS, whereas both the depth and rate of respiration increased in panic disorder. Cardiac output was decreased in POTS but increased in those with panic [97].

Hypermobile Ehlers-Danlos syndrome (hEDS) – In addition to classic musculoskeletal and skin findings, patients with the hypermobile type of Ehlers-Danlos syndrome may report orthostatic intolerance or other autonomic symptoms. A number of studies have reported a relationship of POTS with hEDS [98-103].

Data associating POTS and hEDS are limited by variations in study methodology, manner of assessment of orthostatic symptoms, and subsequent advances in knowledge about these syndromes. Some patients would no longer be classified as POTS by current heart rate criteria for adolescents [85,104] or as hEDS by the more stringent established criteria for hEDS [105,106]. A consistent finding has been orthostatic symptoms in at least 40 percent of patients with generalized joint hypermobility [98-102,107]. Connective tissue laxity has been hypothesized to affect vascular wall compliance, leading to venous pooling [101], but the mechanism for orthostatic intolerance in a significant proportion of patients with joint hypermobility has not been established. Hypermobile Ehlers-Danlos syndrome is discussed in detail separately. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder".)

Mast cell activation syndrome (MCAS) – Flushing, which can occur in POTS, also occurs in patients with MCAS. In one report of 177 POTS patients, eight patients had episodes of flushing along with elevated urinary methylhistamine levels suggestive of MCAS (serum tryptase levels, a more specific marker of MCAS, were not reported) [108]. However, flushing in MCAS is episodic rather than postural, generalized rather than acral, and cardinal manifestations of MCAS such as urticaria, angioedema, or bronchial airway constriction are not features of POTS [106-111]. A causative association of MCAS with POTS lacks evidence-based support [106]. Mast cell activation syndromes are discussed separately. (See "Mast cell disorders: An overview", section on 'Mast cell activation syndrome'.)

Spontaneous intracranial hypotension – Orthostatic headache is one of the symptoms of orthostatic intolerance as well as the hallmark feature of spontaneous intracranial hypotension. Patients with POTS may report orthostatic headaches [54,112]. Additionally, in one instance, orthostatic headaches with postural tachycardia was due to spontaneous intracranial hypotension from cerebrospinal fluid leak [113].

Chiari malformation – While some patients with Chiari I malformation may report dizziness or other symptoms suggestive of orthostatic intolerance, there is no evidence for an association of POTS with the descended cerebellar tonsils in Chiari malformation [114]. (See "Causes of vertigo", section on 'Chiari malformation'.)

MANAGEMENT — The therapeutic strategy for POTS relies on symptom management through intravascular volume expansion, physical exercise, and lifestyle changes as well as compressive garments. Pharmacologic agents may be needed in more severe cases. Data supporting recommendations are limited to small studies using heterogeneous diagnostic criteria and varied duration of follow-up or from expert consensus opinion [115].

Initial treatment strategies — We suggest increasing fluid and salt intake and advise an exercise regimen with targeted lifestyle modifications for the initial treatment of most patients with POTS.

Water and salt intake — Oral fluid intake should be encouraged to a target of 3 L daily and a daily salt intake of 8 to 12 g of sodium chloride (3.2 to 4.8 g of sodium) [55,84,104,116]. Available sources of sodium include table salt, sports tablets, sports beverages, oral rehydration salts, and some soups. The long-term effects on blood pressure of increased sodium intake in POTS are unknown [93,117].

Intravenous boluses of 1 to 2 L of normal saline can be used for hypovolemic patients unable to tolerate liberalization of fluids by mouth to help improve orthostatic symptoms for up to two days [118-120]. This strategy may be used as a short-term bridge to enable the patient to engage in physical exercise and other lifestyle modifications [51,121]. Long-term administration of intravenous saline infusions through an indwelling central venous port is discouraged because of the potential risks of venous thrombosis, bacteremia, and systemic infections [90,104,116,122].

Exercise — Patients with POTS benefit from an incremental program of aerobic exercise. Many patients with POTS are physically deconditioned and others are at risk for deconditioning by restricting their physical activity to manage POTS symptoms [15,55,123].

Despite intolerance of exercise in the upright position, many patients are successful in beginning an exercise program in a semirecumbent position, such as with a recumbent bicycle, with a rowing machine, or in a swimming pool. Exercise rehabilitation for POTS should include lower extremity resistance strength training, which helps to reduce venous pooling [15]. Supervised training may be needed for patients who cannot adhere to an exercise program on their own or believe exercise to be too difficult [124]. An approach that has worked well starts with training sessions three to four times per week for 30 to 40 minutes per session. During these sessions, exercise intensity is individualized to achieve 70 to 75 percent of maximal predicted heart rate. As fitness improves, patients should be able gradually to increase the duration, intensity, and frequency of exercise and advance to exercising in the upright posture [125].

The benefits of exercise in POTS have been demonstrated in small studies. In one study involving 31 military recruits with symptoms of orthostatic intolerance, those assigned to an exercise regimen were less likely to report orthostatic symptoms at three months [126]. In another study, 19 patients with POTS assigned to a three-month exercise training program (consisting of 30- to 45-minute sessions two to four times weekly) showed improved cardiovascular responses to exercise, lower heart rates, and faster heart rate recovery after exercise compared with baseline [127]. Among 103 patients who completed a program of mild-to-moderate intensity progressive endurance training, 71 percent went into remission and no longer met the diagnostic criteria for POTS [125].

Lifestyle management — Behavioral and environmental changes may help reduce systemic (nonorthostatic) symptoms. The efficacy of these strategies has not been evaluated systematically in POTS patients but may provide adjunctive benefit to many patients. Such strategies include the following:

Encourage patients to be upright as much as possible during the day and to avoid prolonged bedrest, which can lead to further deconditioning.

Manage catastrophizing, anxiety, and functional disability with counseling and cognitive behavioral therapy [63,128]. (See "Overview of psychotherapies", section on 'Cognitive and behavioral therapies'.)

Develop physical habits to reduce triggering symptoms. As examples, lower extremity muscle tensing, leg crossing, and weight shifting engage the skeletal "muscle pump" to improve venous return and can provide immediate temporary symptom relief.

Improve sleep quality by having a consistent bedtime and wake time, not spending time in bed during the day, winding down prior to going to bed, and ensuring that the bedroom environment promotes sleep [129].

Adjunctive treatment options — In patients with severe symptoms and those whose symptoms persist in spite of initial treatment strategies, we add compressive garments and medications to the management regimen. Individual options among choices are guided by patient preferences and concomitant medical comorbidities.

Compressive garments — We use graded compressive stockings or abdominal binders to reduce symptoms related to venous pooling. Waist-high stockings at 30 to 40 mmHg or abdominal binders at 10 mmHg ameliorate lower extremity and splanchnic venous pooling, respectively, but higher pressures do not provide further benefit [130].

Lower-extremity compressive garments avoid risk of adverse effects associated with medications but are not always tolerated, as they can be uncomfortable to wear. The use of an abdominal binder is better tolerated and convenient because it can be applied when the patient is upright and is easily removed at other times [130]. Compression of the abdomen may be more beneficial in reducing venous pooling than compression of the legs because of the higher venous capacitance of the splanchnic mesenteric bed, which is the largest of the body's venous reservoirs, accounting for one-third of the total blood volume [131,132].

Medications — The use of medications to treat POTS is based on severity of the patient's symptoms and response to other treatments. We start medications at a low dose and titrate slowly, as patients with POTS are often sensitive to medications, and doses effective for POTS are typically lower than the doses at which these medications are used for other conditions.

Initial medication choice is guided by targeting the underlying mechanism and by patient medical comorbidities. A general rationale is provided here, with specific drug recommendations listed further below. For most patients, our approach to selecting initial pharmacotherapy includes:

Beta blockers for patients without contraindicating comorbid medical conditions to reduce orthostatic tachycardia

Vasopressor therapy for patients who have neuropathic (eg, sudomotor or acral vasomotor) symptoms [20,84]

Avoiding medications that inhibit norepinephrine uptake for patients with evidence of a hyperadrenergic state

However, there is no specific pharmacologic algorithm that applies to all patients. For an individual patient, it may be necessary to try several approaches in succession. We commonly use beta blockers, midodrine, fludrocortisone, or pyridostigmine and reserve the other medications listed below in select severe or refractory cases.

Beta blockers – Beta adrenergic receptor antagonists can blunt elevations in heart rate and are therefore used frequently in patients with POTS. Propranolol and metoprolol have been studied the most in POTS but have not been compared, and there is no consensus as to whether a beta-1 selective or nonselective beta blocker is superior in the treatment of POTS. For some patients, fatigue is a limiting side effect.

Metoprolol 0.25 to 0.5 mg/kg given twice daily reduced symptoms in nearly 80 percent of children and adolescents in a systematic review of 249 patients [133].

Propranolol was effective at 20 mg daily in attenuating both tachycardia and symptom burden in a study of 54 patients [134]. A higher dose of 80 mg elicited a greater reduction in heart rate but with less net improvement of symptoms.

MidodrineMidodrine, an alpha adrenoreceptor agonist, is used at 2.5 to 10 mg three times daily. The medication should be administered in the morning, midday, and late afternoon when the patient is in the upright position.

Midodrine constricts arteriolar and venous capacitance vessels and reduces blood pooling. A crossover study found that midodrine up to 10 mg three times daily improved postural tachycardia in patients with decreased adrenergic vasoconstriction [135]. In a nonblinded trial of 53 adolescents with POTS, midodrine at 2.5 mg once daily was superior to metoprolol 0.5 mg/kg daily or increased salt and water intake, with 89 percent efficacy during three to six months of follow-up despite the very low dose used [136]. Cutaneous paresthesia is a common side effect. Although supine hypertension is a recognized adverse effect of midodrine when used to treat neurogenic orthostatic hypotension, this seldom occurs when used for POTS [135].

Fludrocortisone – The mineralocorticoid fludrocortisone is used at 0.05 to 0.2 mg daily. Patients should be monitored for hypokalemia and elevated blood pressure in the supine position while taking fludrocortisone.

Fludrocortisone temporarily expands intravascular volume by temporarily promoting renal sodium reabsorption and increases peripheral vascular resistance by sensitizing peripheral blood vessel alpha adrenoreceptors to circulating catecholamines [137,138]. One survey of POTS patients found that fludrocortisone improved nausea in half of 16 POTS patients but without significant improvement in orthostatic symptoms [139].

PyridostigminePyridostigmine enhances sympathetic ganglionic transmission and is given at doses of 30 to 60 mg up to three times daily.

In a small randomized crossover study, POTS patients receiving 30 mg pyridostigmine reported decreased symptoms within four hours and had decreased standing heart rates [140]. In a retrospective study of 300 POTS patients, approximately half reported improvement in orthostatic symptoms on pyridostigmine [4].

DroxidopaDroxidopa is a prodrug of norepinephrine that can be administered orally to induce peripheral vasoconstriction. Droxidopa is given 100 mg three times daily, in the morning, midday, and late afternoon, and is best held when patients are recumbent to reduce the risk of supine hypertension. It may be titrated up to 600 mg three times daily for efficacy as symptoms and blood pressure tolerability permit.

In a retrospective study of 37 patients with POTS who were treated off-label with droxidopa at 100 to 600 mg three times daily, 27 percent reported improved quality of life; however, 41 percent stopped the drug due to adverse effects or ineffectiveness [141].

Ivabradine – Several case series have reported lowering of heart rate and symptomatic improvement in more than half of patients treated with ivabradine at 2.5 to 20 mg/day in one to two doses [142-145]. In a small crossover trial of 22 patients with POTS and an elevated baseline norepinephrine level, those assigned to ivabradine given at 2.5 mg to 7.5 mg twice daily (titrated to achieve resting supine heart rate <70 beats/minute) over one month had reduced heart rate and reported improved symptoms compared with those assigned to placebo [146].

Methylphenidate – As a postsynaptic alpha receptor agonist, methylphenidate releases stored catecholamines. Methylphenidate may be started at 10 mg twice daily and increased as needed every few weeks to 30 mg twice daily. In a retrospective study of 24 POTS patients, methylphenidate given as 10 mg three times daily was associated with improvement of presyncope and fatigue in 14 patients [147].

Special circumstances

Surgery in POTS patients — No guidelines or systemic studies are available to direct optimal perioperative management of POTS patients. However, a number of recommendations are offered based on POTS pathophysiology. Intravenous fluid boluses can compensate for preoperative oral fluid restriction. Patients taking fludrocortisone should be monitored for hypokalemia. Epinephrine and combined alpha-beta receptor agonists should be used with caution, as they may worsen tachycardia [148].

The effects of general anesthetic agents in POTS patients have not been well studied, but there is no evidence that any one agent is superior to another [148]. In a series of 13 POTS patients who underwent surgery with general anesthesia, three patients experienced prolonged intraoperative hypotension, but not tachycardia, that occurred during the course of anesthesia and not at the time of induction [149].

If prolonged immobilization is necessary postoperatively, early physical therapy is useful to prevent worsening of orthostatic symptoms through deconditioning.

POTS and pregnancy — Limited data suggest a varied effect of pregnancy on POTS symptoms. During the third trimester of pregnancy, pressure of the uterus against the inferior vena cava can reduce cardiac preload and contribute to orthostatic symptoms. A study of 22 POTS patients who carried pregnancies to term found that orthostatic symptoms worsened in 7, remained unchanged in 3, and improved in 12 [150].

Nonpharmacologic therapy is appropriate. Salt supplementation should be continued unless contraindicated by hypertension [151]. Exercise regimens and other medication options should be discussed with the patient and her obstetrician prior to implementing.

Treatment not recommended — Several interventions have previously been used for POTS patients that have been shown to lack efficacy, risk harm, or both.

Radiofrequency sinus node modification is not recommended for treatment of tachycardia in POTS, as such treatment often worsens symptoms [104].

There is insufficient evidence to recommend vagal nerve stimulation in POTS [152].

There is neither evidence nor scientific rationale for the use of endovascular procedures on the thoracic venous system in the treatment of POTS [153].

PROGNOSIS — Most patients with POTS improve with treatment or spontaneously. In one prospective study, orthostatic symptoms improved at one year follow-up in most patients, and more than one-third no longer met tilt-table criteria for POTS [154].

However, POTS is a chronic condition, and many patients may be subject to occasional flares or recurrences of orthostatic symptoms [49]. In a survey of 502 patients with POTS at a mean of 5.4 years after diagnosis, 19 percent reported complete resolution of symptoms, 51 percent reported persistent but improved symptoms, and 16 percent reported intermittent continued symptoms [155].

POTS does not increase the risk of mortality [49,116].

SUMMARY AND RECOMMENDATIONS

Definition and terminology – Postural tachycardia syndrome (POTS) is a disorder of orthostatic tolerance. Orthostatic intolerance describes an abnormal autonomic response causing symptoms that develop while sustaining an upright posture. The clinical syndrome of POTS includes intermittent symptoms of orthostatic intolerance accompanied by excessive tachycardia without arterial hypotension. (See 'Introduction and terminology' above.)

Mechanisms – In POTS, a variety of pathophysiologic conditions may lead to a final common pathway of orthostatic intolerance with tachycardia. These include hypovolemia and deconditioning, neuroendocrine dysfunction, autonomic neuropathy, and autoimmunity. More than one mechanism may be present in a given patient. (See 'Mechanisms' above.)

Clinical features

Orthostatic intolerance – Symptoms of orthostatic intolerance in patients with POTS are brought on by standing and are relieved by sitting down. They typically include lightheadedness, palpitations, fading of vision, presyncope, and headache. (See 'Clinical features' above.)

Nonorthostatic symptoms – Many patients with POTS also report symptoms that are unrelated to postural changes. Symptoms may be intermittent or constant and include anxiety, fatigue, resting or nocturnal paroxysmal tachycardia, and acrocyanosis. Anxiety is common in POTS but appears phenomenologically distinct from symptoms of generalized anxiety disorder or panic disorder. (See 'Symptoms unrelated to orthostasis' above.)

Diagnosis – The diagnosis of POTS is made by (see 'Diagnostic criteria' above):

History of symptoms of orthostatic intolerance with or without systemic symptoms

Correlation of symptoms with a sustained increase in upright heart rate by at least 30 beats/minute (40 beats/minute for patients under the age of 20 years) within 10 minutes of standing or head-up tilt, without orthostatic hypotension

Autonomic testing to correlate symptoms with heart rate changes, confirm the diagnosis, and assess the degree of objective signs of orthostatic intolerance

Other diagnostic testing as needed to exclude alternative diagnoses or confounding concomitant conditions

Initial conservative management – The therapeutic strategy for POTS relies on symptom management. For most patients with POTS, we suggest conservative interventions such as increasing fluid and salt intake, a regular exercise regimen, and targeted lifestyle modifications (Grade 2C). (See 'Initial treatment strategies' above.)

Adjunctive treatments – In patients with severe symptoms and those whose symptoms persist in spite of initial treatment strategies, we add compressive garments and medications to the management regimen. Individual options among choices is guided by patient preferences and concomitant medical comorbidities. (See 'Adjunctive treatment options' above.)

There is no specific pharmacologic algorithm that applies to all patients. We commonly use beta blockers, midodrine, fludrocortisone, or pyridostigmine and reserve the other medications listed above in select severe or refractory cases. (See 'Medications' above.)

Prognosis – Most patients with POTS improve with treatment or spontaneously. However, many patients may be subject to occasional flares or recurrences of orthostatic symptoms. (See 'Prognosis' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Horacio Kaufmann, MD and Roy Freeman, MD, who contributed to earlier versions of this topic review.

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Topic 5100 Version 27.0

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