Pediatric Annals

Special Issue Article 

Postural Tachycardia Syndrome: Diagnosis and Management in Adolescents and Young Adults

Geoffrey L. Heyer, MD

Abstract

Postural tachycardia syndrome (POTS) represents a common form of orthostatic intolerance that disproportionately affects young women from puberty through adulthood. Patients with POTS have day-to-day orthostatic symptoms with the hallmark feature of an excessive, sustained, and symptomatic rise in heart rate during orthostatic testing. Although considerable overlap exists, three subtypes of POTS have been described: neuropathic, hyperadrenergic, and hypovolemic forms. The wide spectrum of symptoms and comorbidities can make treatment particularly challenging. Volume expansion with fluid and salt, exercise, and education constitute a reasonable initial therapy for most patients. Several medicines are also available to treat orthostatic intolerance and the associated comorbidities. Defining the POTS subtypes clinically in each patient may help to guide medicine choices. A multidisciplinary approach to overall management of the patient with POTS is advised. This review highlights several aspects of POTS with a specific focus on adolescent and young adult patients. [Pediatr Ann. 2017;46(4):e145–e154.]

Abstract

Postural tachycardia syndrome (POTS) represents a common form of orthostatic intolerance that disproportionately affects young women from puberty through adulthood. Patients with POTS have day-to-day orthostatic symptoms with the hallmark feature of an excessive, sustained, and symptomatic rise in heart rate during orthostatic testing. Although considerable overlap exists, three subtypes of POTS have been described: neuropathic, hyperadrenergic, and hypovolemic forms. The wide spectrum of symptoms and comorbidities can make treatment particularly challenging. Volume expansion with fluid and salt, exercise, and education constitute a reasonable initial therapy for most patients. Several medicines are also available to treat orthostatic intolerance and the associated comorbidities. Defining the POTS subtypes clinically in each patient may help to guide medicine choices. A multidisciplinary approach to overall management of the patient with POTS is advised. This review highlights several aspects of POTS with a specific focus on adolescent and young adult patients. [Pediatr Ann. 2017;46(4):e145–e154.]

In 1871, Da Costa published a case series of American Civil War soldiers who developed symptomatic increases in heart rate with standing, often after a diarrheal illness, fever, or heavy combat and injury.1 Soldiers as young as age 16 years were reported. Da Costa referred to the malady as “Irritable Heart.” Over the years, the terminology has evolved as recognition of the syndrome continued.2 More contemporary reports have focused on the associated physiological features, including elevated serum norepinephrine levels and diminished plasma volumes.3–5 In 1993, Schondorf and Low6 formally defined the idiopathic postural orthostatic tachycardia syndrome among adults. Stewart et al.7 were the first to report adolescent patients in 1999.

Orthostatic intolerance refers to the inability to tolerate standing or upright posture (orthostasis) due to symptoms that are relieved by recumbency. Postural tachycardia syndrome (POTS) represents a common form of orthostatic intolerance, estimated to affect at least 500,000 people in the United States.8 Young women of childbearing age are disproportionately affected. Symptoms can develop after the onset of puberty or after an illness or injury, or they can occur without a clear trigger. This review highlights several diagnostic and treatment aspects of POTS with a specific focus on adolescent and young adult patients.

Normal Standing

When humans assume an upright posture, gravity stresses the regulatory capabilities of the circulatory system. During normal standing, gravity causes the downward displacement of blood into distensible blood vessels of the splanchnic vascular bed, pelvis, and lower extremities, which reduces venous return to the heart and causes a transient decline in arterial pressure. Prolonged standing leads to microvascular filtration of plasma into the interstitium, further reducing blood volume.9

Several physiological countermeasures help the body to defend against the effects of gravity with standing. These include the skeletal “muscle pump” and the baroreflex. Upon standing, the skeletal muscles that support upright posture also compress veins in the legs, pelvis, and abdomen, propelling blood return to the heart.10 Movement of the lower extremities creates a muscle-pumping effect, which is augmented by the abdominal-respiratory muscles.11 The concomitant baroreflex response activates the sympathetic system, while inhibiting the parasympathetic system, resulting in increased heart rate and contractility, increased vascular resistance, and modulation of other neuroendocrine responses. Failure of one or more of these compensatory mechanisms during normal standing can cause orthostatic intolerance.

Pots Definition and Diagnosis

The heart rate normally increases with standing. The hallmark of POTS is an excessive, sustained, and symptomatic rise in heart rate with upright posture (Figure 1A). The sinus tachycardia occurs without corresponding hypotension (Figure 1B) and in the absence of other conditions that can cause tachycardia (eg, medicines, anemia, dehydration, or thyroid disease). Among adults, the POTS diagnosis requires a heart rate increment of ≥30 beats per minute (bpm) or an absolute heart rate ≥120 bpm during the first 10 minutes of head-upright tilt or standing test.6,12–15 Singer et al.16 demonstrated that healthy children have higher heart rate changes during testing and recommended revised diagnostic criteria, including (1) a symptomatic heart rate increment ≥40 bpm and (2) an absolute heart rate ≥130 bpm (for age ≤13 years and younger) or ≥120 bpm (age 14 to 19 years), within the first 5 minutes of head-up tilt. The POTS diagnosis should also include a history of chronic, day-to-day orthostatic symptoms such as lightheadedness, palpitations, nausea, sweating, tremulousness, headaches, anxiety, and the sensation of near-syncope.17


            The figure demonstrates (A) a sustained elevation in heart rate without (B) hypotension for the first 10 minutes (600 seconds) of upright tilt. The blood pressure began to drop at about 800 seconds until neurally mediated (cardioinhibitory) syncope at about 900 seconds. The patient reported several orthostatic symptoms that progressed through the study.

Figure 1.

The figure demonstrates (A) a sustained elevation in heart rate without (B) hypotension for the first 10 minutes (600 seconds) of upright tilt. The blood pressure began to drop at about 800 seconds until neurally mediated (cardioinhibitory) syncope at about 900 seconds. The patient reported several orthostatic symptoms that progressed through the study.

The testing protocols for POTS vary across institutions. The original diagnostic criteria were established using tilt-table testing.6 Plash et al.15 validated an active standing protocol in adults. They included 60 minutes of recumbency prior to standing, which may have improved test sensitivity. An analogous study of standing has not yet been done in children. Passive tilt differs from active standing by allowing patients to assume an upright posture with minimal activation of the skeletal muscle pump. Whereas standing may represent the more physiologic form of orthostatic challenge, standardization of a standing test, with minimization of movement, can be challenging. Muscle contraction and postural sway during standing can alter hemodynamics.18–20 Some younger patients and those with anxiety can have difficulties standing calmly with tilt testing or standing test. Table 1 provides an example of a standing test protocol for the office screenig of POTS. Additional studies that can complement the orthostatic challenge include tests of autonomic function (sudomotor sweat test and measures of sympathetic and parasympathetic tone), exercise testing,21,22 and laboratory testing (eg, recumbent and upright norepinephrine levels, 24-hour urine sample, thyroid panel, and complete blood counts).


            Postural Tachycardia Syndrome Screening Testa

Table 1.

Postural Tachycardia Syndrome Screening Test

Pots Mimics

Bedrest

Prolonged bedrest can produce a POTS phenotype. Whether bedrest should be considered a cause of POTS or a mimic of POTS remains debated. Astronauts experience orthostatic intolerance after returning from long-term exposure to microgravity associated with spaceflight.23,24 Prolonged bedrest can emulate the microgravity environment and cause cardiovascular deconditioning with cardiac atrophy, diminished blood volume, atrophy of the skeletal muscle pump, and impaired vasoconstriction.17,25–27 Exercise coupled with volume expansion can lead to substantial symptom improvements, with resolution of the orthostatic tachycardia in some patients.28 Conversely, the lack of exercise and normal upright activity among patients with POTS can perpetuate a vicious cycle of more bedrest, less upright activity, and worsening of orthostatic tolerance.

Hypovolemia and Anemia

Anemia or acute dehydration can cause symptomatic tachycardia with standing. Correcting the underlying disorder should improve symptoms. Some overlap exists where patients with POTS have a chronic hypovolemic state with day-to-day orthostatic symptoms.

Syncope

Some patients with POTS experience neurally mediated syncope, but syncope is not a defining characteristic of POTS. Although the sensation of pre-syncope is commonly described, loss of consciousness from syncope is not a day-to-day feature.17 When patients present with daily fainting, numerous fainting episodes per day, or atypical fainting semiologies, psychogenic nonsyncopal collapse (also referred to as pseudosyncope) should be considered.29,30

Medicines

A variety of medicines can alter the autonomic or hemodynamic response to orthostasis. Table 2 lists some common drug types and some specific medicine examples. The list is not exhaustive. Some listed medicines have multiple drug mechanisms. Accurate orthostatic testing (tilt test or standing test) requires that these medicines be held ≥5 half-lives. When a medicine cannot be held for clinical reasons, the test results should be interpreted cautiously.


            Common Medications that Can Alter the Autonomic or Hemodynamic Response During Testing

Table 2.

Common Medications that Can Alter the Autonomic or Hemodynamic Response During Testing

Anxiety and Hyperventilation

The relationships between anxiety, hyperventilation, and orthostatic intolerance are complex. Patients with POTS, particularly those with the hyperadrenergic phenotype, can have a sense of anxiety, palpitations, tremulousness, and hyperventilation that are induced by tilt-table testing and that improve with recumbency. Studying adolescents and young adults with POTS, Del Pozzi et al.31 demonstrated that reduced cerebral blood flow velocities preceded hyperventilation and activation of the sympathetic system during tilt testing. Yet, patients with anxiety disorder also can experience hyperventilation and POTS-like symptoms of heart racing and lightheadedness. Excessive hyperventilation can cause tachycardia in healthy people. Anxiety is the more likely diagnosis when the orthostatic heart rate can be decreased by coaching the patient to relax his or her breathing. Sweating patterns and other objective measures of anxiety may prove useful in disentangling these complex interactions.32

Pots Subtypes

POTS is a heterogeneous disorder that represents a final common pathway for a number of overlapping pathophysiologies.21,33–37 Three POTS subtypes have been described: the neuropathic or denervated form, the hyperadrenergic form, and the hypovolemic form. Although clinical features overlap, characterizing the POTS subtype in each patient may help inform the approach to treatment.38–41

Neuropathic POTS

The neuropathic form of POTS features partial sympathetic denervation of the lower body, which causes impaired vasoconstriction in the lower extremities42,43 or splanchnic blood vessels,44,45 decreased norepinephrine spillover in the legs (compared to the arms),42 abnormal distal sweat responses with sudomotor testing,37,46,47 and decreased small-fiber densities on skin biopsy.48 The neuropathic phenotype corresponds with the POTS subgroups referred to as “high-flow” while recumbent35 and “hyperdynamic” during exercise,22 each reflecting the failure of normal vasoconstriction. A defect in arteriolar vasoconstriction, not an abnormality of venous capacitance, causes the excessive blood pooling.36,49 The redistribution of central blood volume to the legs when upright results in decreased venous return to the heart, with compensatory tachycardia and sympathetic activation.

In a large series of predominantly adult patients with POTS, 54% had evidence of denervation.47 Rates in pediatric populations have not been published. Clinical signs can overlap, but these patients tend to have lower resting heart rates, lower tilted heart rates, less anxiety and depression, and reduced parasympathetic function when compared to patients with POTS without signs of denervation.37 Acrocyanosis, the bluish-purple discoloration of the extremities when standing, suggests the neuropathic subtype. Patients can have elevated serum norepinephrine levels (measured from the arms), even though norepinephrine spillover in the legs is diminished.42 Midodrine promotes vasoconstriction and appears to be a particularly suitable treatment of neuropathic POTS.38

Hyperadrenergic POTS

The hyperadrenergic subtype refers to patients with POTS and excessive serum norepinephrine levels with standing (≥600 pg/mL).50–54 Whereas normal standing causes an increase in sympathetic nerve activity mediated by the baroreflex, patients with POTS can have an amplified response.52 Additionally, hypovolemia can decrease cardiac output and, in turn, decrease norepinephrine clearance, leading to a hyperadrenergic state.

In the absence of hypovolemia (including relative hypovolemia due to blood pooling), the mechanism accounting for increased norepinephrine is not clear. In both recumbent and upright positions, plasma concentrations of norepinephrine, epinephrine, and dopamine were higher among patients with POTS compared to healthy controls.34 The hyperadrenergic POTS subtype corresponds with the so-called “low-flow” POTS variant35 and the “hypokinetic” circulation during exercise,21 each reflecting the disproportionate degree of vasoconstriction. Studies have shown elevated angiotensin-II levels55 and impairment of nitric oxide-mediated vasodilation56,57 in these patients. The defect in vasodilation is corrected by angiotensin-II receptor blockade.58 Interestingly, the increases in angiotensin-II levels correlate with lower body-mass indexes.59 Low body weight is common among adolescents with POTS. Clinical features that suggest a hyperadrenergic subtype include elevated heart rate (upright and recumbent), elevated blood pressure, pallor, exaggerated tremors, anxiety, and cold, sweaty extremities.34,53,60,61 When present, the possibility of hyperthyroidism or a catecholamine-secreting tumor, such as pheochromocytoma, should be considered.62 Disordered mast cell activation and mutation of the norepinephrine transporter can cause hyperadrenergic POTS phenotypes (discussed below).

Volume expansion and medicines that decrease the production or effects of norepinephrine may be particularly helpful for patients with hyperadrenergic POTS. Given the chronic vasoconstricted state, medicines that promote further vasoconstriction such as midodrine may be undesirable.38

Hypovolemic POTS

Compared to healthy controls, patients with POTS can have lower plasma volumes,63–65 lower red blood cell volumes,66,67 or both.50,68 The renin-angiotensin-aldosterone system is fundamental in regulating blood volume, in large part by promoting renal retention of sodium and water. A hypovolemic state should activate this system, yet the hypovolemia present among POTS patients is accompanied by inappropriately low levels of plasma renin activity and aldosterone,50,63,64 with substantially elevated levels of angiotensin-II.51,55 This has been referred to as the “renin-aldosterone paradox,”50 and its cause is not known. Volume expansion and treatment of the hyperadrenergic state (when present) are reasonable first-line treatment approaches.

Norepinephrine-Transporter Deficiency

The primary mechanism for norepinephrine inactivation in the synaptic cleft is pre-synaptic reuptake by a norepinephrine transporter. Dysfunction of the transporter can cause a hyperadrenergic POTS phenotype characterized by postural tachycardia, elevated serum norepinephrine, lightheadedness, fatigue, altered mentation, and syncope.69,70 Shannon et al.69 identified a heterozygous mutation in the norepinephrine-transporter gene (SLC6A2) that resulted in more than 98% loss of function as compared to the wild-type gene. Medicines such as atomoxetine that selectively inhibit the norepinephrine transporter can produce a hyperadrenergic POTS-like effect.71

Mast Cell Activation Disorder

Idiopathic mast cell activation is independent of mastocytosis.72 The disorder can present with a hyperadrenergic POTS phenotype characterized by episodic flushing, lightheadedness, shortness of breath, headache, excessive diuresis, diarrhea, nausea, vomiting, and elevated urine N-methylhistamine (>230 mcg/g creatinine) during the flushing episode.73 Histamine is a potent vasodilator, and its episodic release in close proximity to blood vessels and peripheral nerves could alter sympathetic activity and vascular tone. Treatments include mast cell stabilizers and H1- and H2-antihistamines. Use of beta-blockers should be avoided.73

Duplications and triplications of the gene encoding alpha-tryptase (TPSAB1) produces a similar phenotype with multisystem complaints of episodic flushing, pruritus, dysautonomia, functional gastrointestinal symptoms, joint hypermobility, and elevated basal serum tryptase levels.74 People harboring alleles encoding three copies of alpha-tryptase were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect.74

Autoimmunity

An infection can precede the onset of POTS in some patients.47 The infection trigger plus evidence of subacute denervation in some patients has led investigators to search for an autoimmune mechanism. Elevated ganglionic-receptor-binding antibodies were detected in a single adult patient (out of 15) with POTS.75 Antibodies that cross-react with various cardiac proteins have been identified.76,77 Adult patients with POTS were found to possess alpha-1AR, beta-1AR, or beta-2AR antibodies that activate or block their corresponding receptors.78,79 These discoveries may open new avenues for POTS diagnosis and treatment, but they require further study before routine clinical use.

Deconditioning

Cardiovascular deconditioning is defined as an ineffective or inefficient response to physical exercise due to inactivity.80 Not all patients with POTS and high exercise heart rates are deconditioned; some have a hyperkinetic circulation (described above) with relative tachycardia, but normal stroke volumes.22 The laboratory definition of deconditioning relies on the percent maximum oxygen uptake (VO2max) during exercise testing. For example, patients between 65% and 85% VO2max may be considered mildly deconditioned, wheras those below 65% VO2max are severely deconditioned.81 The reduced VO2max occurs in the setting of maximal exercise effort, low cardiac stroke volumes, and relative tachycardia. In studies of adolescents and adults with POTS, the rates of deconditioning varied from 42% to >90% and related, in part, to the types of exercise performed and the specific laboratory definitions used.81–84 It is not clear whether deconditioning is a cause or consequence of POTS, but it is clear that reconditioning is beneficial and should be advocated.17

Comorbidities

Patients with POTS tend to have various other associated features that are not clearly orthostatic in nature, meaning that they are not typically provoked by upright positioning nor diminished by recumbency. The various comorbidities include chronic pain, fatigue, joint hypermobility, sleep disturbances, headache, anxiety, depression, inattention, nausea, gastroparesis, and various functional gastrointestinal complaints.85–95 How these comorbidities relate to POTS requires further study. Chelimsky et al.87 showed that the comorbid conditions are not specific to the POTS diagnosis. Yet, one could hypothesize indirect relationships related, for example, to the hyperadrenergic state. Duplications and triplications of the TPSAB1 gene (described above) appear to tie together joint hypermobility with a POTS phenotype in a small number of patients.74 It is likely that future discoveries will help us to understand the physiological links between POTS and its common comorbidities.

Treatment

There is no single, effective treatment for POTS. The wide spectrum of symptoms and comorbidities can make treatment particularly challenging. Education about the disorder is an important first step. The treatments below are divided into nonpharmacological and pharmacological. This is not meant to imply that all nonmedical interventions must be exhausted before medicine can be introduced. However, it is reasonable to first recommend volume expansion (salt and fluid), initiation of an exercise routine, and good sleep hygiene. Arguably, a patient who denies any symptom improvements with aggressive volume expansion may have other factors contributing to symptom persistence. A multidisciplinary treatment approach is often helpful.

Nonpharmacological Treatments

Regardless of the underlying mechanism causing POTS, diminished venous return to the heart while upright contributes to the symptomatic tachycardia. Accordingly, volume expansion with salt and fluid is a crucial first step in therapy. Urine should appear clear after the first morning void. Salty foods should be sought out from meals and snacks. Salt tablets can help to provide a salt load first thing in the morning and during periods in the day where it would be inconvenient to eat a meal. Some clinicians emphasize specific salt dosing, but day-to-day effect is probably a more valuable (and realistic) guide.

The use of chronic intravenous (IV) saline has become a common, albeit unfortunate, approach to volume expansion. As expected, IV saline infusion decreases recumbent and upright heart rates96 and improves symptoms during tilt.97 However, I do not recommend chronic IV hydration for several reasons: the effect is fleeting; oral hydration is usually equivalent; the risks of infection and blood clot from line placement far outweigh the potential benefits; and IV hydration over-medicalizes the simple act of drinking and eating, which can negatively affect disease-coping skills and life quality. I recommend IV hydration only during the brief periods when illness, nausea, or vomiting may prevent adequate oral intake.

Exercise is considered a cornerstone of POTS treatment that confers overall health benefits, regardless of the presence or degree of deconditioning. A short-term exercise program can increase baroreflex sensitivity, decrease upright heart rate,98 increase plasma volume,99 and improve day-to-day symptoms.99 The benefits appear to be longstanding.100 How to begin an exercise routine depends, in part, on the patient's exercise tolerance at the time of diagnosis. Physical therapy can be helpful when moderate-to-severe deconditioning is present.

Additional nonpharmacological interventions include education about good sleep hygiene, biofeedback and coping skills training, counseling, tracking and avoiding symptom triggers, and avoidance of medicines that can worsen orthostatic intolerance. Compression stockings (waste-high, 20-30 mm Hg)101 can be helpful for brief periods when prolonged standing is expected (eg, choir performance).

Pharmacological Treatments

The evidence to guide customized medication choices for POTS is limited.102

Fludrocortisone is a synthetic mineralocorticoid and potent aldosterone agonist that increases renal retention of sodium (and water). Optimal effects are achieved when salt is supplemented. Fludrocortisone improves the hemodynamic impairment of POTS, presumably by improving volume status.4,40 Due to the potassium wasting effects, potassium supplementation should be considered, especially with higher doses.

Midodrine, an alpha1-adrenergic agonist, causes vasoconstriction that may be particularly beneficial for patients with the neuropathic POTS subtype.38 The half-life of midodrine is short, so dosing is usually 3 times daily. Potential side effects include goose bumps, tingling, and urinary retention. Recumbent hypertension can occur, especially when midodrine is combined with medicines such as fludrocortisone. Octreotide, a somatostatin analog, has several physiological effects, including vasoconstriction of the splanchnic vascular bed. Octreotide improved tachycardia and standing times in POTS with potency similar to midodrine.5,103 However, combining octreotide and midodrine was no better than monotherapy.103

Pyridostigmine acts by inhibiting acetylcholinesterase, slowing the hydrolysis of acetylcholine in the synaptic cleft, and increasing parasympathetic tone. Oral pyridostigmine (30 mg) significantly decreased standing heart rate at 2 hours and 4 hours without changing blood pressure.104 Symptoms improved at 4 hours compared to placebo. Side effects relate to excessive cholinergic activity.

Propranolol at low doses (20 mg) reduced standing heart rates and improved orthostatic symptoms.39 It also improved exercise capacity by reducing peak heart rate and increasing stroke volume.105 Yet daily use of a long-acting propranolol formulation did not improve quality of life at 1 month.106 Esmolol infusion did not significantly reduce acute tachycardia.41 Beta-blockers may be most suitable for patients with a hyperadrenergic POTS subtype, but they should be avoided when mast cell activation disorders are suspected.73 Clonidine, an alpha-2 receptor agonist, reduces standing norepinephrine levels and may increase plasma volumes, but it can also decrease orthostatic blood pressure.97,107 A low, night-time dose may help with sleep initiation in hyperadrenergic POTS.

Ivabradine acts on the so-called “funny” channel current (If) that is highly expressed in the sinoatrial node, slowing heart rate without affecting blood pressure. A retrospective study suggests potential therapeutic benefits in POTS,108 but further investigation is needed.

Desmopressin is a synthetic analog of arginine vasopressin. It decreased standing heart rate and improved symptoms compared to placebo.109 But hyponatremia is a potential complication when used long-term.

Current evidence does not support the routine use of erythropoietin in POTS treatment.68,110 Stimulants should be used cautiously. Atomexetine, an inhibitor of the norepinephrine reuptake transporter, acutely worsens POTS symptoms.71 Modafinil increases heart rate, blood pressure, and orthostatic norepinephrine levels.111

Placebo Effect

POTS treatment trials have demonstrated a placebo effect where the placebo resulted in lower orthostatic heart rates.38,104,109 That a placebo effect can occur underscores the notion that POTS represents a complex psychophysiological disorder, with possible similarities to migraine.112,113

Outcomes

There is a paucity of outcome data for adolescents and young adults with POTS. Given the heterogeneous nature of the disorder, the specific POTS subtype and associated comorbidities probably influence long-term prognosis. A survey of adolescents (mean 5.4 years after the POTS diagnosis) indicates a high rate of symptom improvement or resolution.114 A study of young adults with POTS, an average of 92 ± 41 months after diagnosis, suggested similar improvements.115

Conclusion

POTS is a common form of orthostatic intolerance among adolescents and young adults. It is characterized by day-to-day orthostatic symptoms and an excessive, sustained, and symptomatic rise in heart rate during orthostatic testing. Defining POTS subtypes clinically may help to guide the approach to treatment, although overlap between subtypes exists. Future research is needed to better understand the complex psychophysiological nature of POTS and to discover its underlying causes.

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Postural Tachycardia Syndrome Screening Testa

Standing-test protocol to screen for POTS in adolescent patients <list-item>

Record baseline heart rate and blood pressure while patient is recumbent ≥10 minutes

</list-item><list-item>

Ask patient to stand in place calmly for 10 minutes

</list-item><list-item>

Record heart rate and blood pressure every 2 minutes or monitor continuously

</list-item><list-item>

Encourage reporting of symptoms

</list-item><list-item>

Recommend sitting if fainting seems imminent

</list-item>
Consider the diagnosis of POTS when all of the following are present <list-item>

Sustained rise in heart rate of 40 bpm or absolute heart rate of 120 bpm

</list-item><list-item>

Orthostatic symptoms correspond with a rise in heart rate and resolve with recumbency

</list-item><list-item>

Blood pressure does not drop ≥20 mm Hg systolic or ≥10 mm Hg diastolic

</list-item><list-item>

Patient has longstanding, day-to-day symptoms

</list-item><list-item>

Medicines that can alter hemodynamics were held at least five half-lives prior to testing

</list-item><list-item>

No signs of anemia, acute dehydration, or hyperventilation (while standing)

</list-item>

Common Medications that Can Alter the Autonomic or Hemodynamic Response During Testing

Serotonin-norepinephrine reuptake inhibitors <list-item>

Venlafaxine

</list-item><list-item>

Desvenlafaxine

</list-item><list-item>

Duloxetine

</list-item>
Norepinephrine reuptake inhibitors <list-item>

Bupropion

</list-item><list-item>

Nortriptyline

</list-item><list-item>

Desipramine

</list-item>
Atomoxetine Anticholinergics <list-item>

Amitriptyline

</list-item><list-item>

Cyclobenzaprine

</list-item><list-item>

Dicyclomine

</list-item><list-item>

Hyoscyamine

</list-item>
Stimulants <list-item>

Methylphenidate

</list-item><list-item>

Amphetamine enantiomer

</list-item><list-item>

Modafinil

</list-item>
Alpha-1 adrenergic receptor agonists <list-item>

Midodrine

</list-item><list-item>

Phenylephrine

</list-item>
Alpha-2 adrenergic receptor agonists <list-item>

Clonidine

</list-item><list-item>

Guanfacine

</list-item>
Beta-adrenergic receptor blockers Calcium-channel blockers Phosphodiesterase inhibitors Acetylcholinesterase inhibitors Diuretics Angiotensin-converting enzyme inhibitors Phenothiazines Butyrophenones Lithium salts Benzodiazepines
Authors

Geoffrey L. Heyer, MD, is an Associate Professor, Division of Pediatric Neurology, Nationwide Children's Hospital.

Address correspondence to Geoffrey L. Heyer, MD, Division of Pediatric Neurology, Nationwide Children's Hospital, 700 Children's Drive, ED-5, Columbus, OH 43205; email: geoffrey.heyer@nationwidechildrens.org

Disclosure: The author has no relevant financial relationships to disclose.

10.3928/19382359-20170322-01

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