Derek S. Chew, MD

Article Type

Article

Changed

Wed, 05/01/2019 - 07:59

Display Headline

Evaluating and managing postural tachycardia syndrome

Author(s)

Lucy Y. Lei

Derek S. Chew, MD

Robert S. Sheldon, MD, PhD

Satish R. Raj, MD, MSCI, FRCPC

Some people, most of them relatively young women, experience lightheadedness, a racing heart, and other symptoms (but not hypotension) when they stand up, in a condition known as postural tachycardia syndrome (POTS).¹ Although not known to shorten life,¹ it can be physically and mentally debilitating.^2,3 Therapy rarely cures it, but a multifaceted approach can substantially improve quality of life.

This review outlines the evaluation and diagnosis of POTS and provides guidance for a therapy regimen.

HOW IS POTS DEFINED?

POTS is a multifactorial syndrome rather than a specific disease. It is characterized by all of the following^1,4–6:

An increase in heart rate of ≥ 30 bpm, or ≥ 40 bpm for those under age 19, within 10 minutes of standing from a supine position
Sustained tachycardia (> 30 seconds)
Absence of orthostatic hypotension (a fall in blood pressure of ≥ 20/10 mm Hg)
Frequent and chronic duration (≥ 6 months).

These features are critical to diagnosis. Hemodynamic criteria in isolation may describe postural tachycardia but are not sufficient to diagnose POTS.

The prevalence of POTS is estimated to be between 0.2% and 1.0%,⁷ affecting up to 3 million people in the United States. Most cases arise between ages 13 and 50, with a female-to-male ratio of 5:1.⁸

MANY NAMES, SAME CONDITION

In 1871, Da Costa⁹ described a condition he called “irritable heart syndrome” that had characteristics similar to those of POTS, including extreme fatigue and exercise intolerance. Decades later, Lewis¹⁰ and Wood¹¹ provided more detailed descriptions of the disorder, renaming it “soldier’s heart” or “Da Costa syndrome.” As other cases were documented, more terms arose, including “effort syndrome” and “mitral valve prolapse syndrome.”

In 1982, Rosen and Cryer¹² were the first to use the term “postural tachycardia syndrome” for patients with disabling tachycardia upon standing without orthostatic hypotension. In 1986, Fouad et al¹³ described patients with postural tachycardia, orthostatic intolerance, and a small degree of hypotension as having “idiopathic hypovolemia.”

In 1993, Schondorf and Low¹⁴ established the current definition of POTS, leading to increased awareness and research efforts to understand its pathophysiology.

MULTIFACTORIAL PATHOPHYSIOLOGY

During the last 2 decades, several often-overlapping forms of POTS have been recognized, all of which share a final common pathway of sustained orthostatic tachycardia.^15–19In addition, a number of common comorbidities were identified through review of large clinic populations of POTS.^20,21

Hypovolemic POTS

Up to 70% of patients with POTS have hypovolemia. The average plasma volume deficit is about 13%, which typically causes only insignificant changes in heart rate and norepinephrine levels while a patient is supine. However, blood pooling associated with upright posture further compromises cardiac output and consequently increases sympathetic nerve activity. Abnormalities in the renin-angiotensin-aldosterone volume regulation system are also suspected to impair sodium retention, contributing to hypovolemia.^1,22

Neuropathic POTS

About half of patients with POTS have partial sympathetic denervation (particularly in the lower limbs) and inadequate vasoconstriction upon standing, leading to reduced venous return and stroke volume.^17,23 A compensatory increase in sympathetic tone results in tachycardia to maintain cardiac output and blood pressure.

Hyperadrenergic POTS

Up to 50% of patients with POTS have high norepinephrine levels (≥ 600 pg/mL) when upright. This subtype, hyperadrenergic POTS, is characterized by an increase in systolic blood pressure of at least 10 mm Hg within 10 minutes of standing, with concomitant tachycardia that can be similar to or greater than that seen in nonhyperadrenergic POTS. Patients with hyperadrenergic POTS tend to report more prominent symptoms of sympathetic activation, such as palpitations, anxiety, and tremulousness.^24,25

Norepinephrine transporter deficiency

The norepinephrine transporter (NET) is on the presynaptic cleft of sympathetic neurons and serves to clear synaptic norepinephrine. NET deficiency leads to a hyperadrenergic state and elevated sympathetic nerve activation.¹⁸ NET deficiency may be induced by common antidepressants (eg, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors) and attention-deficit disorder medications.⁴

Mast cell activation syndrome

The relationship between mast cell activation syndrome and POTS is poorly understood.^4,26 Mast cell activation syndrome has been described in a subset of patients with POTS who have sinus tachycardia accompanied by severe episodic flushing. Patients with this subtype have a hyperadrenergic response to postural change and elevated urine methylhistamine during flushing episodes.

Patients with mast cell activation syndrome tend to have strong allergic symptoms and may also have severe gastrointestinal problems, food sensitivities, dermatographism, and neuropathy. Diagnosis can be difficult, as the condition is associated with numerous markers with varying sensitivity and specificity.

Autoimmune origin

A significant minority of patients report a viral-like illness before the onset of POTS symptoms, suggesting a possible autoimmune-mediated or inflammatory cause. Also, some autoimmune disorders (eg, Sjögren syndrome) can present with a POTS-like manifestation.

Research into the role of autoantibodies in the pathophysiology of POTS offers the potential to develop novel therapeutic targets. Autoantibodies that have been reported in POTS include those against M1 to M3 muscarinic receptors (present in over 87% of patients with POTS),²⁷ cardiac lipid raft-associated proteins,²⁸ adrenergic G-protein coupled receptors, alpha-1-adrenergic receptors, and beta-1- and beta-2-adrenergic receptors.²⁹ Although commercial enzyme-linked immunosorbent assays can assess for these antibody fragments, it is not known whether targeting the antibodies improves outcomes. At this time, antibody testing for POTS should be confined to the research setting.

LINKS TO OTHER SYNDROMES

POTS is often associated with other conditions whose symptoms cannot be explained by postural intolerance or tachycardia.

Ehlers-Danlos syndromes are a group of inherited heterogeneous disorders involving joint hypermobility, skin hyperextensibility, and tissue fragility.³⁰ The hypermobile subtype is most commonly associated with POTS, with patients often having symptoms of autonomic dysregulation and autonomic test abnormalities.^31–33 Patients with POTS may have a history of joint subluxations, joint pain, cervical instability, and spontaneous epidural leaks. The reason for the overlap between the two syndromes is not clear.

Chronic fatigue syndrome is characterized by persistent fatigue that does not resolve with rest and is not necessarily associated with orthostatic changes. More than 75% of patients with POTS report general fatigue as a major complaint, and up to 23% meet the full criteria for chronic fatigue syndrome.³⁴

DIAGNOSTIC STRATEGY

A patient presenting with symptoms suggestive of POTS should first undergo a detailed history and physical examination. Other causes of sinus tachycardia should be considered.

Detailed history, symptom review

The history should focus on determining symptom burden, including tachycardia onset, frequency, severity, and triggers; the presence of syncope; and the impact of symptoms on daily function and quality of life.

Typical symptoms of postural tachycardia syndrome

POTS-associated orthostatic intolerance manifests with cardiac and noncardiac symptoms (Table 1).

Presyncope and its associated symptoms occur in less than one-third of patients with POTS, and syncope is not a principal feature.⁴ If syncope is the predominant complaint, alternative causes should be investigated. The usual cause of syncope in the general population is thought to be vasovagal.

In addition to orthostatic intolerance, gastrointestinal disturbances are common in POTS, presenting as abdominal pain, heartburn, irregular bowel movements, diarrhea, or constipation. Symptoms of gastroparesis are less common. Gastrointestinal symptoms tend to be prolonged, lasting hours and occurring multiple times a week. They tend not to improve in the supine position.³⁵

POTS-associated symptoms may develop insidiously, but patients often report onset after an acute stressor such as pregnancy, major surgery, or a presumed viral illness.⁴Whether these putative triggers are causative or coincidental is unknown. Symptoms of orthostatic intolerance tend to be exacerbated by dehydration, heat, alcohol, exercise, and menstruation.^36,37

Consider the family history: 1 in 8 patients with POTS reports familial orthostatic intolerance,³⁸suggesting a genetic role in some patients. Inquire about symptoms or a previous diagnosis of Ehlers-Danlos syndrome and mast cell activation syndrome.

Consider other conditions

Differential diagnosis of postural tachycardia syndrome symptoms

Other causes of orthostatic tachycardia are listed in Table 2.^39–41 Most can be diagnosed with a careful history, physical examination, and laboratory tests. Two of the more challenging diagnoses are described below.

Pheochromocytoma causes hyperadrenergic symptoms (eg, palpitations, lightheadedness) like those in POTS, but patients with pheochromocytoma typically have these symptoms while supine. Pheochromocytoma is also characterized by plasma norepinephrine levels much higher than in POTS.⁴ Plasma metanephrine testing helps diagnose or rule out pheochromocytoma.⁵

Inappropriate sinus tachycardia, like pheochromocytoma, also has clinical features similar to those of POTS, as well as tachycardia present when supine. It involves higher sympathetic tone and lower parasympathetic tone compared with POTS; patients commonly have a daytime resting heart rate of at least 100 bpm or a 24-hour mean heart rate of at least 90 bpm.^1,42 While the intrinsic heart rate is heightened in inappropriate sinus tachycardia, it is not different between POTS patients and healthy individuals.^42,43 Distinguishing POTS from inappropriate sinus tachycardia is further complicated by the broad inclusion criteria of most studies of inappropriate sinus tachycardia, which failed to exclude patients with POTS.⁴⁴The Heart Rhythm Society recently adopted distinct definitions for the 2 conditions.¹

Physical examination: Focus on vital signs

Figure 1. Results of head-up tilt-table (HUT) testing in a healthy person (top) and in a patient with postural tachycardia syndrome (POTS) (bottom). Upon passive head-up tilting, the heart rate increases in POTS by at least 30 bpm but remains largely stable in healthy individuals. Orthostatic hypotension (a fall in blood pressure of ≥ 20/10 mm Hg) does not occur in either patient.

The most critical component of the physical examination is thorough measurement of orthostatic vital signs (Figure 1). Blood pressure and heart rate should be measured while the patient has been supine for at least 5 minutes, and again after being upright for 1, 3, 5, and 10 minutes. These measurements determine if orthostatic hypotension is present and whether the patient meets the heart rate criteria for POTS. Patients with POTS tend to experience greater orthostatic tachycardia in the morning, so evaluation early in the day optimizes diagnostic sensitivity.⁵

Dependent acrocyanosis—dark red-blue discoloration of the lower legs that is cold to the touch—occurs in about half of patients with POTS upon standing.⁴ Dependent acrocyanosis is associated with joint hypermobility and Ehlers-Danlos syndrome, so these conditions should also be considered if findings are positive.

Laboratory testing for other causes

Laboratory testing is used mainly to detect primary causes of sinus tachycardia. Tests should include:

Complete blood cell count with hematocrit (for severe anemia)
Thyroid-stimulating hormone level (for hyperthyroidism)
Electrolyte panel (for significant electrolyte disturbances).

Evidence is insufficient to support routinely measuring the vitamin B₁₂ level, iron indices, and serum markers for celiac disease, although these may be done if the history or physical examination suggests related problems.⁴ Sicca symptoms (severe dry eye or dry mouth) should trigger evaluation for Sjögren syndrome.

Electrocardiography needed

Electrocardiography should be performed to investigate for cardiac conduction abnormalities as well as for resting markers of a supraventricular tachyarrhythmia. Extended ambulatory (Holter) monitoring may be useful to evaluate for a transient reentrant tachyarrhythmia⁴; however, it does not record body position, so it can be difficult to determine if detected episodes of tachycardia are related to posture.

Additional testing for select cases

Further investigation is usually not needed to diagnose POTS but should be considered in some cases. Advanced tests are typically performed at a tertiary care referral center and include:  

Quantitative sensory testing to evaluate for small-fiber neuropathy (ie, Quantitative Sudomotor Axon Reflex Test, or QSART), which occurs in the neuropathic POTS subtype
Formal autonomic function testing to characterize neurovascular responsiveness
Supine and standing plasma norepinephrine levels (fractionated catecholamines) to characterize the net activation of the sympathetic nervous system
Blood volume assessments to assess hypovolemia
Formal exercise testing to objectively quantify exercise capacity.

GRADED MANAGEMENT

No single universal gold-standard therapy exists for POTS, and management should be individually determined with the primary goals of treating symptoms and restoring function. A graded approach should be used, starting with conservative nonpharmacologic therapies and adding medications as needed.

While the disease course varies substantially from patient to patient, proper management is strongly associated with eventual symptom improvement.¹

NONPHARMACOLOGIC STEPS FIRST

Nonpharmacologic treatments for postural tachycardia syndrome

A multipronged nonpharmacologic approach should be used for all patients before resorting to medications (Table 3). In an observational study, most patients reported that such interventions were more helpful than medications.⁴⁵The following elements are recommended:

Education

Patients should be informed of the nature of their condition and referred to appropriate healthcare personnel. POTS is a chronic illness requiring individualized coping strategies, intensive physician interaction, and support of a multidisciplinary team. Patients and family members can be reassured that most symptoms improve over time with appropriate diagnosis and treatment.¹ Patients should be advised to avoid aggravating triggers and activities.

Exercise

Exercise programs are encouraged but should be introduced gradually, as physical activity can exacerbate symptoms, especially at the outset. Several studies have reported benefits from a short-term (3-month) program, in which the patient gradually progresses from non-upright exercise (eg, rowing machine, recumbent cycle, swimming) to upright endurance exercises. At the end of these programs, significant cardiac remodeling, improved quality of life, and reduced heart rate responses to standing have been reported, and benefits have been reported to persist in patients who continued exercising after the 3-month study period.^46,47

Despite the benefits of exercise interventions, compliance is low.^46,47 To prevent early discouragement, patients should be advised that it can take 4 to 6 weeks of continued exercise before benefits appear. Patients are encouraged to exercise every other day for 30 minutes or more. Regimens should primarily focus on aerobic conditioning, but resistance training, concentrating on thigh muscles, can also help. Exercise is a treatment and not a cure, and benefits can rapidly disappear if regular activity (at least 3 times per week) is stopped.⁴⁸

Compression stockings

Compression stockings help reduce peripheral venous pooling and enhance venous return to the heart. Waist-high stockings with compression of at least 30 to 40 mm Hg offer the best results.

Diet

Increased fluid and salt intake is advisable for patients with suspected hypovolemia. At least 2 to 3 L of water accompanied by 10 to 12 g of daily sodium intake is recommended.¹ This can usually be accomplished with diet and salt added to food, but salt tablets can be used if the patient prefers. The resultant plasma volume expansion may help reduce the reflex tachycardia upon standing.⁴⁹

Check medications

Medications that can exacerbate postural tachycardia syndrome

The clinician should review—and perhaps discontinue—medications the patient is already taking that may exacerbate tachycardia or related symptoms (Table 4).⁵⁰Venodilators decrease preload, thereby reducing cardiac output and blood pressure, which triggers compensatory tachycardia. Diuretics can reduce effective blood volume and lower preload, leading to worsened symptoms mediated by hypovolemia.

Rescue therapy with saline infusion

Intravenous saline infusion can augment blood volume in patients who are clinically decompensated and present with severe symptoms.¹ Intermittent infusion of 1 L of normal saline has been found to significantly reduce orthostatic tachycardia and related symptoms in patients with POTS, contributing to improved quality of life.^51,52

Chronic saline infusions are not recommended for long-term care because of the risk of access complications and infection.¹ Moak et al⁵³ reported a high rate of bacteremia in a cohort of children with POTS with regular saline infusions, most of whom had a central line. On the other hand, Ruzieh et al⁵⁴reported significantly improved symptoms with regular saline infusions without a high rate of complications, but patients in this study received infusions for only a few months and through a peripheral intravenous catheter.

DRUG THERAPY

Pharmacologic treatments for postural tachycardia syndrome

Drug therapy for POTS should be used only if nonpharmacologic interventions do not adequately relieve symptoms. Given the heterogeneity of POTS, treatment should be tailored to the patient’s underlying pathophysiology, key clinical features, and comorbidities. These considerations should guide the initial selection of medications, with adjustments as needed to alleviate adverse effects (Table 5).

No medications are approved by the US Food and Drug Administration (FDA) or Health Canada specifically for treating POTS, making all pharmacologic recommendations off-label. Although the drugs discussed below have been evaluated for POTS in controlled laboratory settings, they have yet to be tested in robust clinical trials.

Blood volume expansion

Several drugs expand blood volume, which may reduce orthostatic tachycardia.

Fludrocortisone is a synthetic aldosterone analogue that enhances sodium and water retention. Although one observational study found that it normalizes hemodynamic changes in response to orthostatic stress, no high-level evidence exists for its effectiveness for POTS.⁵⁵ It is generally well tolerated, although possible adverse effects include hyperkalemia, hypertension, fatigue, nausea, headache, and edema.^5,56

Desmopressin is a synthetic version of a natural antidiuretic hormone that increases kidney-mediated free-water reabsorption without sodium retention. It significantly reduces upright heart rate in patients with POTS and improves symptom burden. Although potential adverse effects include edema and headache, hyponatremia is the primary concern with daily use, especially with the increased water intake advised for POTS.⁵⁷ Patients should be advised to use desmopressin no more than once a week for the acute improvement of symptoms. Intermittent monitoring of serum sodium levels is recommended for safety.

Erythropoietin replacement has been suggested for treating POTS to address the significant deficit in red blood cell volume. Although erythropoietin therapy has a direct vasoconstrictive effect and largely improves red blood cell volume in patients with POTS, it does not expand plasma volume, so orthostatic tachycardia is not itself reduced.²² Nevertheless, it may significantly improve POTS symptoms refractory to more common methods of treatment, and it should be reserved for such cases. In addition to the lack of effect on orthostatic tachycardia, drawbacks to using erythropoietin include its high cost, the need for subcutaneous administration, and the risk of life-threatening complications such as myocardial infarction and stroke.^58,59

Heart rate-lowering agents

Propranolol, a nonselective beta-adrenergic antagonist, can significantly reduce standing heart rate and improve symptoms at low dosages (10–20 mg). Higher dosages can further restrain orthostatic tachycardia but are not as well tolerated, mainly due to hypotension and worsening of existing symptoms such as fatigue.⁶⁰ Regular-acting propranolol works for about 4 to 5 hours per dose, so full-day coverage often requires dosing 4 times per day.

Ivabradine is a selective blocker of the “funny” (I_f) channel that reduces the sinus node firing rate without affecting blood pressure, so it slows heart rate without causing supine hypertension or orthostatic hypotension.

A retrospective case series found that 60% of patients with POTS treated with ivabradine reported symptomatic improvement, and all patients experienced reduced tachycardia with continued use.⁶¹ Ivabradine has not been compared with placebo or propranolol in a randomized controlled trial, and it has not been well studied in pregnancy and so should be avoided because of potential teratogenic effects.

When prescribing ivabradine for women of childbearing age, a negative pregnancy test may be documented prior to initiation of therapy, and the use of highly effective methods of contraception is recommended. Ivabradine should be avoided in women contemplating pregnancy. Insurance coverage can limit access to ivabradine in the United States.

Central nervous system sympatholytics

Patients with prominent hyperadrenergic features may benefit from central sympatholytic agents. However, these drugs may not be well tolerated in patients with neuropathic POTS because of the effects of reduced systemic vascular resistance⁵ and the possible exacerbation of drowsiness, fatigue, and mental clouding.⁴ Patients can be extremely sensitive to these medications, so they should initially be prescribed at the lowest dose, then gradually increased as tolerated.

Clonidine, an alpha-2-adrenergic agonist, decreases central sympathetic tone. In hyperadrenergic patients, clonidine can stabilize heart rate and blood pressure, thereby reducing orthostatic symptoms.⁶²

Methyldopa has effects similar to those of clonidine but is easier to titrate owing to its longer half-life.⁶³Methyldopa is typically started at 125 mg at bedtime and increased to 125 mg twice daily, if tolerated.

Other agents

Midodrine is a prodrug. The active form, an alpha-1-adrenergic agonist, constricts peripheral veins and arteries to increase vascular resistance and venous return, thereby reducing orthostatic tachycardia.⁵² It is most useful in patients with impaired peripheral vasoconstriction (eg, neuropathic POTS) and may be less effective in those with hyperadrenergic POTS.⁶⁴ Major limitations of midodrine include worsening supine hypertension and possible urinary retention.³⁹

Because of midodrine’s short half-life, frequent dosing is required during daytime hours (eg, 8 AM, noon, and 4 PM), but it should not be taken within 4 to 5 hours of sleep because of the risk of supine hypertension. Midodrine is typically started at 2.5 to 5 mg per dose and can be titrated up to 15 mg per dose.

Midodrine is an FDA pregnancy category C drug (adverse effects in pregnancy seen in animal models, but evidence lacking in humans). While ideally it should be avoided, we have used it safely in pregnant women with disabling POTS symptoms.

Pyridostigmine, an acetylcholinesterase inhibitor, increases cardiovagal tone and possibly sympathetic tone. It has been reported to significantly reduce standing heart rate and improve symptom burden in patients with POTS.⁶⁵ However, pyridostigmine increases gastrointestinal mobility, leading to severe adverse effects in over 20% of patients, including abdominal cramps, nausea, and diarrhea.⁶⁶

Droxidopa, a synthetic amino acid precursor of norepinephrine, improves dizziness and fatigue in POTS with minimal effects on blood pressure.⁶⁷

Modafinil, a psychostimulant, may improve POTS-associated cognitive symptoms.⁴ It also raises upright blood pressure without significantly worsening standing heart rate or acute orthostatic symptoms.⁶⁸

EFFECTS OF COMORBID DISORDERS ON MANAGEMENT

Ehlers-Danlos syndrome

Pharmacologic approaches to POTS should not be altered based on the presence of Ehlers-Danlos syndrome, but because many of these patients are prone to joint dislocation, exercise prescriptions may need adjusting.

A medical genetics consult is recommended for patients with Ehlers-Danlos syndrome. Although the hypermobile type (the form most commonly associated with POTS) is not associated with aortopathy, it can be confused with classical and vascular Ehlers-Danlos syndromes, which require serial aortic screening.³⁰

Mast cell activation syndrome

Consultation with an allergist or immunologist may help patients with severe symptoms.

Autoantibodies and autoimmunity

Treatment of the underlying disorder is recommended and can result in significantly improved POTS symptoms.

SPECIALTY CARE REFERRAL

POTS can be challenging to manage. Given the range of physiologic, emotional, and functional distress patients experience, it often requires significant physician time and multidisciplinary care. Patients with continued severe or debilitating symptoms may benefit from referral to a tertiary-care center with experience in autonomic nervous system disorders.

PROGNOSIS

Limited data are available on the long-term prognosis of POTS, and more studies are needed in pediatric and adult populations. No deaths have been reported in the handful of published cases of POTS in patients older than 50.¹ Some pediatric studies suggest that some teenagers “outgrow” their POTS. However, these data are not robust, and an alternative explanation is that as they get older, they see adult physicians for their POTS symptoms and so are lost to study follow-up.^6,44,69

We have not often seen POTS simply resolve without ongoing treatment. However, in our experience, most patients have improved symptoms and function with multimodal treatment (ie, exercise, salt, water, stockings, and some medications) and time.

References

Sheldon RS, Grubb BP 2nd, Olshansky B, et al. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm 2015; 12(6):e41–e63. doi:10.1016/j.hrthm.2015.03.029
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):204–210. pmid:21509337
Benrud-Larson LM, Dewar MS, Sandroni P, Rummans TA, Haythornthwaite JA, Low PA. Quality of life in patients with postural tachycardia syndrome. Mayo Clin Proc 2002; 77(6):531–537. doi:10.4065/77.6.531
Raj SR. Postural tachycardia syndrome (POTS). Circulation 2013; 127(23):2336–2342. doi:10.1161/CIRCULATIONAHA.112.144501
Raj SR. The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & management. Indian Pacing Electrophysiol J 2006; 6(2):84–99. pmid:16943900
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):222–226. doi:10.1016/j.jpeds.2011.08.054
Mar PL, Raj SR. Neuronal and hormonal perturbations in postural tachycardia syndrome. Front Physiol 2014; 5:220. doi:10.3389/fphys.2014.00220
Garland EM, Raj SR, Black BK, Harris PA, Robertson D. The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome. Neurology 2007; 69(8):790–798. doi:10.1212/01.wnl.0000267663.05398.40
Da Costa JM. On irritable heart: a clinical study of a form of functional cardiac disorder and its consequences. Am J Med Sci 1871; 61(121):2–52.
Lewis T. The tolerance of physical exertion, as shown by soldiers suffering from so-called “irritable heart.” Br Med J 1918; 1(2987):363–365. pmid:20768980
Wood P. Da Costa’s syndrome (or effort syndrome): lecture I. Br Med J 1941; 1(4194):767–772. pmid:20783672
Rosen SG, Cryer PE. Postural tachycardia syndrome. Reversal of sympathetic hyperresponsiveness and clinical improvement during sodium loading. Am J Med 1982; 72(5):847–850.
Fouad FM, Tadena-Thome L, Bravo EL, Tarazi RC. Idiopathic hypovolemia. Ann Intern Med 1986; 104(3):298–303. pmid:3511818
Schondorf R, Low PA. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia? Neurology 1993; 43(1):132–137. pmid:8423877
Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med 2000; 343(12):847–855. doi:10.1056/NEJM200009213431204
Raj SR, Robertson D. Blood volume perturbations in the postural tachycardia syndrome. Am J Med Sci 2007; 334(1):57–60. doi:10.1097/MAJ.0b013e318063c6c0
Jacob G, Costa F, Shannon JR, et al. The neuropathic postural tachycardia syndrome. N Engl J Med 2000; 343(14):1008–1014. doi:10.1056/NEJM200010053431404
Shannon JR, Flattem NL, Jordan J, et al. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med 2000; 342(8):541–549. doi:10.1056/NEJM200002243420803
Jones PK, Shaw BH, Raj SR. Clinical challenges in the diagnosis and management of postural tachycardia syndrome. Pract Neurol 2016; 16(6):431–438. doi:10.1136/practneurol-2016-001405
Gunning WT, Karabin BL, Blomquist TM, Grubb BP. Postural orthostatic tachycardia syndrome is associated with platelet storage pool deficiency. Medicine (Baltimore) 2016; 95(37):e4849. doi:10.1097/MD.0000000000004849
Kanjwal K, Sheikh M, Karabin B, Kanjwal Y, Grubb BP. Neurocardiogenic syncope coexisting with postural orthostatic tachycardia syndrome in patients suffering from orthostatic intolerance: a combined form of autonomic dysfunction. Pacing Clin Electrophysiol 2011; 34(5):549–554. doi:10.1111/j.1540-8159.2010.02994.x
Raj SR, Biaggioni I, Yamhure PC, et al. Renin-aldosterone paradox and perturbed blood volume regulation underlying postural tachycardia syndrome. Circulation 2005; 111(13):1574–1582. doi:10.1161/01.CIR.0000160356.97313.5D
Gibbons CH, Bonyhay I, Benson A, Wang N, Freeman R. Structural and functional small fiber abnormalities in the neuropathic postural tachycardia syndrome. PLoS One 2013; 8(12):e84716. doi:10.1371/journal.pone.0084716
Low PA, Sandroni P, Joyner M, Shen WK. Postural tachycardia syndrome (POTS). J Cardiovasc Electrophysiol 2009; 20(3):352–358. doi:10.1111/j.1540-8167.2008.01407.x
Kanjwal K, Saeed B, Karabin B, Kanjwal Y, Grubb BP. Clinical presentation and management of patients with hyperadrenergic postural orthostatic tachycardia syndrome. A single center experience. Cardiol J 2011; 18(5):527–531. pmid:21947988
Shibao C, Arzubiaga C, Roberts J, et al. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension 2005; 45(3):385–390. doi:10.1161/01.HYP.0000158259.68614.40
Dubey D, Hopkins S, Vernino S. M1 and M2 muscarinic receptor antibodies among patients with postural orthostatic tachycardia syndrome: potential disease biomarker [abstract]. J Clin Neuromuscul Dis 2016; 17(3):179S.
Wang XL, Ling TY, Charlesworth MC, et al. Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome. Transl Res 2013; 162(1):34–44. doi:10.1016/j.trsl.2013.03.002
Li H, Yu X, Liles C, et al. Autoimmune basis for postural tachycardia syndrome. J Am Heart Assoc 2014; 3(1):e000755. doi:10.1161/JAHA.113.000755
Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet 2017; 175(1):8–26. doi:10.1002/ajmg.c.31552
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. doi:10.1016/j.jns.2014.03.002
De Wandele I, Calders P, Peersman W, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls. Semin Arthritis Rheum 2014; 44(3):353–361. doi:10.1016/j.semarthrit.2014.05.013
Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med 2003; 115(1):33–40. pmid:12867232
Okamoto LE, Raj SR, Peltier A, et al. Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes. Clin Sci (Lond) 2012; 122(4):183–192. doi:10.1042/CS20110200
Wang LB, Culbertson CJ, Deb A, Morgenshtern K, Huang H, Hohler AD. Gastrointestinal dysfunction in postural tachycardia syndrome. J Neurol Sci 2015; 359(1-2):193–196. doi:10.1016/j.jns.2015.10.052
Raj S, Sheldon R. Management of postural tachycardia syndrome, inappropriate sinus tachycardia and vasovagal syncope. Arrhythm Electrophysiol Rev 2016; 5(2):122–129. doi:10.15420/AER.2016.7.2
Peggs KJ, Nguyen H, Enayat D, Keller NR, Al-Hendy A, Raj SR. Gynecologic disorders and menstrual cycle lightheadedness in postural tachycardia syndrome. Int J Gynaecol Obstet 2012; 118(3):242–246. doi:10.1016/j.ijgo.2012.04.014
Thieben MJ, Sandroni P, Sletten DM, et al. Postural orthostatic tachycardia syndrome: the Mayo Clinic experience. Mayo Clin Proc 2007; 82(3):308–313. doi:10.4065/82.3.308
Deb A, Morgenshtern K, Culbertson CJ, Wang LB, Hohler AD. A survey-based analysis of symptoms in patients with postural orthostatic tachycardia syndrome. J Am Coll Cardiol 2015; 28(7):157–159. pmid:25829642
Ertek S, Cicero AF. Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology. Arch Med Sci 2013; 9(5):944–952. doi:10.5114/aoms.2013.38685
Rangno RE, Langlois S. Comparison of withdrawal phenomena after propranolol, metoprolol and pindolol. Br J Clin Pharmacol 1982; 13(suppl 2):345S–351S. pmid:6125187
Nwazue VC, Paranjape SY, Black BK, et al. Postural tachycardia syndrome and inappropriate sinus tachycardia: role of autonomic modulation and sinus node automaticity. J Am Heart Assoc 2014; 3(2):e000700. doi:10.1161/JAHA.113.000700
Morillo CA, Klein GJ, Thakur RK, Li H, Zardini M, Yee R. Mechanism of “inappropriate” sinus tachycardia. Role of sympathovagal balance. Circulation 1994; 90(2):873–877. pmid:7913886
Grubb BP. Postural tachycardia syndrome. Circulation 2008; 117(21):2814–2817. doi:10.1161/CIRCULATIONAHA.107.761643
Bhatia R, Kizilbash SJ, Ahrens SP, et al. Outcomes of adolescent-onset postural orthostatic tachycardia syndrome. J Pediatr 2016; 173:149–153. doi:10.1016/j.jpeds.2016.02.035
George SA, Bivens TB, Howden EJ, et al. The international POTS registry: evaluating the efficacy of an exercise training intervention in a community setting. Heart Rhythm 2016; 13(4):943–950. doi:10.1016/j.hrthm.2015.12.012
Fu Q, VanGundy TB, Galbreath MM, et al. Cardiac origins of the postural orthostatic tachycardia syndrome. J Am Coll Cardiol 2010; 55(25):2858–2868. doi:10.1016/j.jacc.2010.02.043
Raj SR. Row, row, row your way to treating postural tachycardia syndrome. Heart Rhythm 2016; 13(4):951–952. doi:10.1016/j.hrthm.2015.12.039
Celedonio JE, Garland EM, Nwazue VC, et al. Effects of high sodium intake on blood volume and catecholamines in patients with postural tachycardia syndrome and healthy females [abstract]. Clin Auton Res 2014; 24:211.
Garland EM, Celedonio JE, Raj SR. Postural tachycardia syndrome: beyond orthostatic intolerance. Curr Neurol Neurosci Rep 2015; 15(9):60. doi:10.1007/s11910-015-0583-8
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
Jacob G, Shannon JR, Black B, et al. Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia. Circulation 1997; 96(2):575–580. pmid:9244228
Moak JP, Leong D, Fabian R, et al. Intravenous hydration for management of medication-resistant orthostatic intolerance in the adolescent and young adult. Pediatr Cardiol 2016; 37(2):278–282. doi:10.1007/s00246-015-1274-6
Ruzieh M, Baugh A, Dasa O, et al. Effects of intermittent intravenous saline infusions in patients with medication-refractory postural tachycardia syndrome. J Interv Card Electrophysiol 2017; 48(3):255–260. doi:10.1007/s10840-017-0225-y
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(5):293–299. pmid:11198485
Lee AK, Krahn AD. Evaluation of syncope: focus on diagnosis and treatment of neurally mediated syncope. Expert Rev Cardiovasc Ther 2016; 14(6):725–736. doi:10.1586/14779072.2016.1164034
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):1484–1490. doi:10.1016/j.hrthm.2012.05.002
Kanjwal K, Saeed B, Karabin B, Kanjwal Y, Sheikh M, Grubb BP. Erythropoietin in the treatment of postural orthostatic tachycardia syndrome. Am J Ther 2012; 19(2):92–95. doi:10.1097/MJT.0b013e3181ef621a
Hoeldtke RD, Horvath GG, Bryner KD. Treatment of orthostatic tachycardia with erythropoietin. Am J Med 1995; 99(5):525–529. pmid:7485211
Raj SR, Black BK, Biaggioni I, et al. Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Circulation 2009; 120(9):725–734. doi:10.1161/CIRCULATIONAHA.108.846501
McDonald C, Frith J, Newton JL. Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. Europace 2011; 13(3):427–430. doi:10.1093/europace/euq390
Gaffney FA, Lane LB, Pettinger W, Blomqvist G. Effects of long-term clonidine administration on the hemodynamic and neuroendocrine postural responses of patients with dysautonomia. Chest 1983; 83(suppl 2):436–438. pmid:6295714
Jacob G, Biaggioni I. Idiopathic orthostatic intolerance and postural tachycardia syndromes. Am J Med Sci 1999; 317(2):88–101. pmid:10037112
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):289–296. doi:10.1042/CS20130222
Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation 2005; 111(21):2734–2340. doi:10.1161/CIRCULATIONAHA.104.497594
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):750–755. doi:10.1111/j.1540-8159.2011.03047.x
Ruzieh M, Dasa O, Pacenta A, Karabin B, Grubb B. Droxidopa in the treatment of postural orthostatic tachycardia syndrome. Am J Ther 2017; 24(2):e157–e161. doi:10.1097/MJT.0000000000000468
Kpaeyeh AG Jr, Mar PL, Raj V, et al. Hemodynamic profiles and tolerability of modafinil in the treatment of POTS: a randomized placebo-controlled trial. J Clin Psychopharmacol 2014; 34(6):738–741. doi:10.1097/JCP.0000000000000221
Lai CC, Fischer PR, Brands CK, et al. Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and beta-blockers. Pacing Clin Electrophysiol 2009; 32(2):234–238. doi:10.1111/j.1540-8159.2008.02207.x

Article PDF

lei_posturaltachycardiasyndrome.pdf

Author and Disclosure Information

Lucy Y. Lei
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Derek S. Chew, MD
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Robert S. Sheldon, MD, PhD
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Satish R. Raj, MD, MSCI, FRCPC
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada; Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN

Address: Satish R. Raj, MD, MSCI, FRCPC, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, GAC70 HRIC Building, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; satish.raj@ucalgary.ca

Dr. Raj has disclosed consulting for Abbott Laboratories, Boston Scientific Corporation, GE Healthcare, and Lundbeck, and serving on the steering committee for the ADMIRE-ICD trial, funded by GE Healthcare.

Issue

Cleveland Clinic Journal of Medicine - 86(5)

Publications

Cleveland Clinic Journal of Medicine

Topics

Cardiology

Neurology

Women's Health

Page Number

333-344

Legacy Keywords

postural tachycardia syndrome, POTS, autonomic nervous system, hypovolemia, hyperadrenergic, norepinephrine, mast cell activation syndrome, Ehlers-Danlos syndromes, tilt table, chronic fatigue syndrome, syncope, Lucy Lei, Derek Chew, Robert Sheldon, Satish Raj

Read more about Evaluating and managing postural tachycardia syndrome

Sections

Author(s)

Robert S. Sheldon, MD, PhD

Satish R. Raj, MD, MSCI, FRCPC

Author(s)

Lucy Y. Lei

Derek S. Chew, MD

Robert S. Sheldon, MD, PhD

Satish R. Raj, MD, MSCI, FRCPC

Author and Disclosure Information

Lucy Y. Lei
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Derek S. Chew, MD
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Robert S. Sheldon, MD, PhD
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Satish R. Raj, MD, MSCI, FRCPC
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada; Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN

Address: Satish R. Raj, MD, MSCI, FRCPC, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, GAC70 HRIC Building, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; satish.raj@ucalgary.ca

Dr. Raj has disclosed consulting for Abbott Laboratories, Boston Scientific Corporation, GE Healthcare, and Lundbeck, and serving on the steering committee for the ADMIRE-ICD trial, funded by GE Healthcare.

Author and Disclosure Information

Lucy Y. Lei
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Derek S. Chew, MD
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Robert S. Sheldon, MD, PhD
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada

Satish R. Raj, MD, MSCI, FRCPC
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada; Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN

Address: Satish R. Raj, MD, MSCI, FRCPC, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, GAC70 HRIC Building, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; satish.raj@ucalgary.ca

Dr. Raj has disclosed consulting for Abbott Laboratories, Boston Scientific Corporation, GE Healthcare, and Lundbeck, and serving on the steering committee for the ADMIRE-ICD trial, funded by GE Healthcare.

Article PDF

lei_posturaltachycardiasyndrome.pdf

Article PDF

lei_posturaltachycardiasyndrome.pdf

Some people, most of them relatively young women, experience lightheadedness, a racing heart, and other symptoms (but not hypotension) when they stand up, in a condition known as postural tachycardia syndrome (POTS).¹ Although not known to shorten life,¹ it can be physically and mentally debilitating.^2,3 Therapy rarely cures it, but a multifaceted approach can substantially improve quality of life.

This review outlines the evaluation and diagnosis of POTS and provides guidance for a therapy regimen.