Postural orthostatic tachycardia syndrome (POTS), first described in 1992, remains an enigmatic, yet severely and variably debilitating, disorder. The pathophysiology of this syndrome is still not understood, and there remains no biomarker indicating the presence of POTS. Although research interest has increased in recent years, there are relatively fewer clinical and research studies addressing POTS in children and adolescents compared with adults. Yet, adolescence is when a large number of cases of POTS begin, even among adult patients who are subsequently studied. This article summarizes reported research in POTS, specifically in pediatric patients, including discussion of aspects of diagnostic criteria, risk factors and outcomes, neurohormonal and hemodynamic abnormalities, clinical assessment, and treatment. The goals of this review are increased recognition and acknowledgment of POTS among pediatric and adolescent providers, as well as to provide an understanding of reported abnormalities of homeostasis, such that symptomatic patients will be able to be recognized and appropriately managed, enabling them to return to their activities of daily living.

Postural orthostatic tachycardia syndrome (POTS), a dysautonomia affecting multiple somatic systems in children and adults, causes significant disability.1,2  POTS has been increasingly recognized since first reported in 1992,3  with steadily increasing numbers of publications since the late 1990s.4  Its relatively high morbidity, plus relatively low research funding prompted the United States National Institutes of Health (NIH) to sponsor a 1-day seminar,5  where international experts in POTS gathered to discuss the state of the science and research priorities.6,7  As 2 of the pediatric representatives to this meeting, J.R.B. and J.P.M. had compiled an extensive medical literature review to discuss the pediatric aspects of POTS. However, as this symposium was not designed as a comprehensive discussion of the literature, the ability to fully compare and contrast pediatric and adult POTS was felt to be addressed better separately. This document will examine various features regarding diagnostic and clinical aspects of POTS in children and adolescents and will summarize specific research findings within these groups.

Take-home points:

  • Patients can have numerous symptoms across multiple body systems.

  • POTS affects predominantly White females in the United States.

  • Diagnostic criteria for pediatric POTS include symptoms of chronic orthostatic intolerance for ≥3 months, persistent symptomatic increase in heart rate by ≥40 beats per minute in the first 10 minutes of upright position after supine position without orthostatic hypotension, and the absence of other potential etiologies. The heart rate criteria may be disputed.

When considering clinical disorders spanning the pediatric and adult age range, it is tempting to contemplate similarities, consider overarching pathophysiologies, create global treatment approaches, and predict prognoses. Manifestations of POTS across ages are similar, with symptoms of chronic orthostatic intolerance,8  tachycardia without orthostatic hypotension, and multiple associated disabling symptoms across multiple body systems (Fig 1)(Table 1). In 1 study, 66% of patients reported at least 10 symptoms, 50% of patients reported ≥14 symptoms, and 30% of patients reported ≥26 symptoms.9  There also has been notable female (3.45:1) and White (94.1%) predominance,9  and association with previous infection or concussion.911  Yet, on closer examination, there are important differences. In children aged 12 to 19, the diagnosis of POTS is, in part, defined from tilt table data as a heart rate increase of ≥40 beats per minute;12  it is unclear if this is valid for a 10-minute standing test. Diagnostic criteria also remain undefined at <12 years.

FIGURE 1

Symptoms associated with POTS. Adapted from Boris JR et al, 2018.9 

FIGURE 1

Symptoms associated with POTS. Adapted from Boris JR et al, 2018.9 

Close modal
TABLE 1

Diagnostic Criteria for POTS

Diagnostic Criteria for POTS
1. A sustained heart rate increment of not less than 30 beats per minute within 10 minutes of standing or head-up tilt. For individuals aged 12–19 y, the required heart rate increment is at least 40 beats per minute; and 
2. An absence of orthostatic hypotension (ie, no sustained systolic blood pressure drop of 20 mmHg or more); and 
3. Frequent symptoms of orthostatic intolerance during standing, with rapid improvement upon return to a supine position. Symptoms may include lightheadedness, palpitations, tremulousness, generalized weakness, blurred vision, and fatigue; and 
4. Duration of symptoms for at least 3 mo; and 
5. Absence of other conditions explaining sinus tachycardia, such as anorexia nervosa, primary anxiety disorders, hyperventilation, anemia, fever, pain, infection, dehydration, hyperthyroidism, pheochromocytoma, use of cardioactive drugs (eg, sympathomimetics, anticholinergics), or severe deconditioning caused by prolonged bed rest. 
Diagnostic Criteria for POTS
1. A sustained heart rate increment of not less than 30 beats per minute within 10 minutes of standing or head-up tilt. For individuals aged 12–19 y, the required heart rate increment is at least 40 beats per minute; and 
2. An absence of orthostatic hypotension (ie, no sustained systolic blood pressure drop of 20 mmHg or more); and 
3. Frequent symptoms of orthostatic intolerance during standing, with rapid improvement upon return to a supine position. Symptoms may include lightheadedness, palpitations, tremulousness, generalized weakness, blurred vision, and fatigue; and 
4. Duration of symptoms for at least 3 mo; and 
5. Absence of other conditions explaining sinus tachycardia, such as anorexia nervosa, primary anxiety disorders, hyperventilation, anemia, fever, pain, infection, dehydration, hyperthyroidism, pheochromocytoma, use of cardioactive drugs (eg, sympathomimetics, anticholinergics), or severe deconditioning caused by prolonged bed rest. 

Adapted from Vernino S et al, 2021.6 

However, there are data that call a threshold heart rate criterion into question. A study by Boris in 2020 demonstrated that frequency of symptoms in children with a heart rate increase between 30 and 39 beats per minute on a 10-minute standing test was not statistically or significantly different from that of patients with a heart rate increase of ≥40 beats per minute13  (Table 2). Another study looking at joint hypermobility syndromes in pediatric patients demonstrated no significant difference in prevalence of joint hypermobility (hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorder) in children with a ≥40 beats per minute heart rate increase on a 10-minute standing test, children with a ≥30 beats per minute increase, or in comparable adult studies.14  Although the original article first documenting that the 95th percentile of heart rate increase in asymptomatic adolescents as 43 beats per minute was performed by tilt table testing,12  subsequently leading to recommendation of a 40 beats per minute threshold for diagnosis of pediatric POTS,15  a study in adults by Plash suggests that the mean increase in heart rate by tilt testing is 7 beats per minute higher than with a 10-minute standing test.16  Furthermore, Medow also showed that pediatric patients with vasovagal syncope had a mean increase in heart rate of 40 beats per minute in nearly half of patients, whereas controls only had a 20 beats per minute increase, despite affected patients not having POTS.17  At the present time, without a biological marker specific to POTS, the consensus is to continue utilizing the increase in heart rate as a major discriminating factor in the diagnosis.15,18  However, paying attention to the multitude and diversity of symptoms in these patients may end up being more important as a discriminator. Once a biological marker is discovered, it may provide for better determination for the presence or absence of disease.

TABLE 2

Research Specific to Pediatric Patients with POTS

Findings in Pediatric Patients with POTSReference
Postconcussion syndrome is associated with pediatric POTS, and a high percentage of POTS-associated tachycardia resolved as postconcussion symptoms improved. 11  
Symptom frequency on 10-min standing test is not significantly different whether heart rate increase is 30–39 or ≥40 beats per minute. 13  
Prevalence of joint hypermobility is not significantly different whether heart rate increase is 30–39 or ≥40 beats per minute. 14  
POTS occurs after growth spurt or menarche. 19  
Symptoms may abate after administration of exogenous testosterone. 20  
As many as 19% of patients with onset of POTS during adolescence had resolution of symptoms. 25  
Up to 48% of pediatric patients were symptom-free at 1-y follow-up, and >85% were symptom-free at 6-y follow-up. 26  
Pediatric patients with POTS are high-achieving in academics and/or athletics. 27  
Flow-mediated vasodilation is greater than in controls. 31  
Nitric oxide levels and nitric oxide synthase activity are elevated as compared with controls. 31  
Hydrogen sulfide levels are greater than in controls. 32  
Resting venous pressures are elevated and arterial resistance is decreased as compared with controls. 33  
Total peripheral vascular resistance and cardiac output are reduced when upright as compared with healthy controls. 34  
C-natriuretic peptide levels are greater than in controls. 34,35  
Resistin levels are elevated compared with controls. 37  
Supine resistin levels are inversely correlated with the degree of heart rate increase from supine to upright. 37  
Copeptin levels are elevated compared with controls. 37 
Antidiuretic hormone levels in patients with hypertension are greater than those without hypertension. 38  
24-h urinary sodium excretion is less than that of controls. 39  
Despite peripheral vasoconstriction, upright position induces splanchnic pooling. 40  
Initial orthostatic hypotension occurs more frequently and with greater severity in patients versus controls. 41  
There is a higher prevalence of altered cerebral blood flow and cardiorespiratory regulation in patients versus controls. 41  
QTc dispersion is longer in patients versus controls. 42  
Rate pressure product in patients is greater before and after awakening versus controls. 43  
Diurnal variation of the heart rate occurs in pediatric POTS. 44  
New-onset motion sickness, lightheadedness as a headache trigger, and orthostatic headache are associated with meeting POTS heart rate criteria in patients with new-onset headache and lightheadedness versus those who do not. 45  
Antroduodenal manometry is most often abnormal in patients with GI symptoms as compared with gastric emptying and endoscopy. 46  
Anorectal manometry is most often abnormal in patients with GI symptoms as compared with gastric emptying, colonic transit, and gastric accommodation. 47  
Patients with GI symptoms and POTS have bradygastria or tachygastria at the gastric antrum and fundus when upright, whereas those without POTS have decreased gastric electrical activity. 48  
In family members of pediatric patients with POTS, 14.2% have POTS, 31.3% have a family member with orthostatic intolerance, 20.2% have a family member with joint hypermobility, and 45.1% have an autoimmune disease. 51  
Symptomatic therapy for pediatric POTS results in efficacy ranging from 39% to 70%, depending upon symptom. 53,54  
Ivabradine improved symptoms in two-thirds of pediatric patients. 55,56  
Midodrine and metoprolol reduced symptoms scores versus untreated patients. 57  
Elevated C-natriuretic peptide and copeptin levels were predictive of efficacy with metoprolol therapy. 35,59  
β blockers and, to a lesser extent, midodrine reduced clinical symptoms of POTS. 60  
Midodrine was effective in the treatment of neuropathic POTS, but not in hyperadrenergic POTS. 61  
Parenteral normal saline reported improved quality of life, but those with permanent access were at risk for thrombosis and/or infection. 62  
Findings in Pediatric Patients with POTSReference
Postconcussion syndrome is associated with pediatric POTS, and a high percentage of POTS-associated tachycardia resolved as postconcussion symptoms improved. 11  
Symptom frequency on 10-min standing test is not significantly different whether heart rate increase is 30–39 or ≥40 beats per minute. 13  
Prevalence of joint hypermobility is not significantly different whether heart rate increase is 30–39 or ≥40 beats per minute. 14  
POTS occurs after growth spurt or menarche. 19  
Symptoms may abate after administration of exogenous testosterone. 20  
As many as 19% of patients with onset of POTS during adolescence had resolution of symptoms. 25  
Up to 48% of pediatric patients were symptom-free at 1-y follow-up, and >85% were symptom-free at 6-y follow-up. 26  
Pediatric patients with POTS are high-achieving in academics and/or athletics. 27  
Flow-mediated vasodilation is greater than in controls. 31  
Nitric oxide levels and nitric oxide synthase activity are elevated as compared with controls. 31  
Hydrogen sulfide levels are greater than in controls. 32  
Resting venous pressures are elevated and arterial resistance is decreased as compared with controls. 33  
Total peripheral vascular resistance and cardiac output are reduced when upright as compared with healthy controls. 34  
C-natriuretic peptide levels are greater than in controls. 34,35  
Resistin levels are elevated compared with controls. 37  
Supine resistin levels are inversely correlated with the degree of heart rate increase from supine to upright. 37  
Copeptin levels are elevated compared with controls. 37 
Antidiuretic hormone levels in patients with hypertension are greater than those without hypertension. 38  
24-h urinary sodium excretion is less than that of controls. 39  
Despite peripheral vasoconstriction, upright position induces splanchnic pooling. 40  
Initial orthostatic hypotension occurs more frequently and with greater severity in patients versus controls. 41  
There is a higher prevalence of altered cerebral blood flow and cardiorespiratory regulation in patients versus controls. 41  
QTc dispersion is longer in patients versus controls. 42  
Rate pressure product in patients is greater before and after awakening versus controls. 43  
Diurnal variation of the heart rate occurs in pediatric POTS. 44  
New-onset motion sickness, lightheadedness as a headache trigger, and orthostatic headache are associated with meeting POTS heart rate criteria in patients with new-onset headache and lightheadedness versus those who do not. 45  
Antroduodenal manometry is most often abnormal in patients with GI symptoms as compared with gastric emptying and endoscopy. 46  
Anorectal manometry is most often abnormal in patients with GI symptoms as compared with gastric emptying, colonic transit, and gastric accommodation. 47  
Patients with GI symptoms and POTS have bradygastria or tachygastria at the gastric antrum and fundus when upright, whereas those without POTS have decreased gastric electrical activity. 48  
In family members of pediatric patients with POTS, 14.2% have POTS, 31.3% have a family member with orthostatic intolerance, 20.2% have a family member with joint hypermobility, and 45.1% have an autoimmune disease. 51  
Symptomatic therapy for pediatric POTS results in efficacy ranging from 39% to 70%, depending upon symptom. 53,54  
Ivabradine improved symptoms in two-thirds of pediatric patients. 55,56  
Midodrine and metoprolol reduced symptoms scores versus untreated patients. 57  
Elevated C-natriuretic peptide and copeptin levels were predictive of efficacy with metoprolol therapy. 35,59  
β blockers and, to a lesser extent, midodrine reduced clinical symptoms of POTS. 60  
Midodrine was effective in the treatment of neuropathic POTS, but not in hyperadrenergic POTS. 61  
Parenteral normal saline reported improved quality of life, but those with permanent access were at risk for thrombosis and/or infection. 62  

Adapted from Boris JR et al, 2018.9  QTc, corrected QT interval.

Take-home points:

  • POTS can start after infection, concussion, growth spurt, or menarche.

  • A small percentage of patients have spontaneous resolution of POTS, meaning that most patients remain at least somewhat affected.

  • Many patients are high-achieving, either academically or athletically, before illness onset.

  • The presence of parental care, plus ensuring that patients take responsibility for their own care, are both important to outcomes of symptomatic management.

Leveraging issues specifically seen in children and adolescents may help with understanding POTS pathophysiology, as the actual pathophysiology in POTS has yet to be defined. Although inadequate peripheral vasoconstriction with compensatory tachycardic response combined with inadequate systemic venous return has been offered a mechanism,6  why this occurs is unclear. POTS is noted to occur after growth spurt or menarche,19  and symptoms may abate after administration of testosterone,20  suggesting a role for sex hormones. There is concern for association with immunization,21  although causation has not been demonstrated and population-based studies have not demonstrated an increase in disease frequency as adolescent vaccination rates have risen.22,23  POTS-like findings have been seen in children with mitochondrial disorders.24  We have anecdotally noted patients with chronic symptoms since infancy or toddlerhood (eg, dysmotility, headaches, or joint hypermobility) who eventually developed POTS later in childhood, with their parents feeling that there was always “something wrong” with them. A 2016 study of patients with POTS with onset during adolescence demonstrated spontaneous resolution of symptoms in up to 19% of patients by the time they reached adulthood.25  However, in these patients, it was noted that POTS symptoms were still present in up to 33% of respondents who had “recovered.” A similar study of long-term outcomes in 2019 from China showed that 48% of pediatric patients with POTS were free of symptoms at 1-year follow-up, with >85% being symptom-free after 6 years,26  although fewer symptoms were used for their assessment than those in other studies.9 

Adolescence, when half of patients with POTS are diagnosed,1  is an important time in which many changes occur in the body, demonstrating significant contrast to adults. During puberty, hormonal changes cause somatic growth, brain maturation, psychological maturation, and gonadal growth and maturation, although it is unclear how these affect the onset, pathophysiology, and outcomes. Children attend school and participate in athletics, whereas adults are more sedentary, and are often high-achieving in either academics and/or athletics.27  Sleep hygiene can be difficult, especially with already recognized differences in adolescent sleep.28  Anecdotally, we have noted patients’ symptoms improving when attending college. This may be because of increased time between classes, with more recovery time, increased neurologic maturity allowing for improved ability to recognize and avoid triggers, or being away from parents, forcing them to accept responsibility and own their disease management. Or it could be simply associated with the aforementioned improvement of symptoms with time.25 

A unique factor that pediatric patients have is parental involvement.29  Parents can be strong advocates, getting these children to a knowledgeable and caring provider, especially when symptoms are ignored or misinterpreted by other providers.1  They network with other parents to optimize their child’s care, and remind or push their children in routine care management. However, parents can generate hindrance to their child’s progress. They may expect rapid return of their (high-achieving) child to school or sports. They may have difficulties allowing their child to mature, or to fail.29  Parents may have their own untreated medical and/or psychological issues influencing their child’s treatment, sometimes feeling compelled to maintain caregiver status as secondary gain.30  They may also not recognize comorbid psychological issues in their children.

Take-home points:

  • Patients with POTS demonstrate abnormal vascular responses, especially with upright position.

  • There are abnormally elevated levels of compounds associated with vasodilation.

  • Significant splanchnic and lower extremity venous pooling occurs in patients.

Research into specific abnormalities found in POTS in children and adolescents is limited because most studies are performed in either adults or a combination of adults and children, but interesting data do exist. Several studies have demonstrated abnormal neurohormonal levels and vascular findings, although these do not necessarily indicate a biological marker specific to POTS. Flow-mediated vasodilation in the brachial artery in children with POTS was found to be greater than that of healthy controls.31  In that same study, plasma concentrations of the vasodilator, nitric oxide, and activity of nitric oxide synthase were elevated. A Chinese study demonstrated that hydrogen sulfide, which can also induce vasodilation, was elevated in pediatric patients with POTS and in those with vasovagal syncope versus healthy controls.32  Adolescents with POTS demonstrate elevated resting venous pressures and decreased arterial resistance.33  Li et al showed that total peripheral vascular resistance and cardiac output were significantly reduced when upright, then normalized while supine, although these measures were unchanged in healthy controls in either position.34  In that same study, C-natriuretic peptide levels were also greater in patients with POTS versus healthy controls. A separate study also confirmed elevated C-natriuretic peptide levels in pediatric patients with overcontrols.35  Serum levels of resistin, a peptide hormone promoting vasoconstriction,36  and copeptin, a glycopeptide closely correlated with vasopressin,37  are noted to be elevated versus controls. Interestingly, supine resistin levels were also found to be inversely correlated with the degree of change of heart rate from supine to upright position.36  Levels of antidiuretic hormone in children with POTS who have hypertension were noted to be higher than that of those without hypertension (397). Another Chinese study demonstrated that 24-hour urinary sodium excretion in children with POTS was significantly less than that of controls.39  In that same study, they attempted to discern patients who would respond to subsequent increased sodium loading by demonstrating decreased symptom scores in patients with persistently low urinary sodium excretion; however, they did not assess this in their control group. Lastly, upright position has been found to induce splanchnic pooling and venous pooling, despite peripheral vasoconstriction.40 

Take-home points:

  • Patients have abnormal cerebral blood flow with upright position.

  • There is significant diurnal variability of upright heart rate response, with worsening morning response.

  • Antroduodenal and anorectal manometry are the most frequently abnormal tests in patients with gastrointestinal (GI) symptoms.

  • Patients with POTS have a higher prevalence of family members with orthostatic intolerance, joint hypermobility, and autoimmune disorders.

From a clinical standpoint, several studies have contributed to better understanding of pediatric POTS. Postconcussion syndrome is associated with pediatric POTS, with a high percentage of resolution of POTS-associated heart rate changes with tilt table as symptoms of postconcussion syndrome improve.11  One finding seen in pediatric patients with POTS is initial orthostatic hypotension, occurring in 51% of patients versus 13% of controls,41  with greater severity and higher prevalence of altered cerebral blood flow and cardiorespiratory regulation. Corrected QT interval dispersion on electrocardiogram is noted to be longer in pediatric patients with POTS versus controls, serving as a marker of a risk factor for the presence of POTS, as well as lower likelihood of success with use of orthostatic training and other physical maneuvers.42  An interesting study of ambulatory blood pressure monitoring in patients and controls showed that the rate pressure product (heart rate times systolic blood pressure) in patients was greater both before and after awakening versus controls,43  with morning increase associated with worsening morning symptoms of orthostatic intolerance. They also demonstrated significant diurnal variability in heart rates of children with POTS, such that all patients met heart rate criteria for the diagnosis of POTS in the morning, but only 28% met those same criteria in the evening.44  In patients evaluated for headaches and lightheadedness, those who met diagnostic criteria for POTS were more likely to have new-onset motion sickness, lightheadedness as a headache trigger, and orthostatic headaches, versus those not meeting heart rate criteria.45 

From a GI standpoint, antroduodenal manometry was found to be the most useful gastroenterologic evaluation versus gastric emptying studies and esophagogastroduodenoscopy, with abnormalities in 81% of pediatric patients demonstrating GI symptoms.46  A retrospective case-control study of gastroenterologic symptoms in pediatric patients with POTS showed that anorectal manometry was also the most frequently abnormal test versus gastric emptying, colonic transit, and gastric accommodation.47  Results from a study assessing electrogastrography in supine versus upright position revealed evidence of bradygastria and tachygastria in the antrum and fundus of patients with POTS when upright on a tilt table, whereas those without POTS but still with GI symptoms had a decrease in abnormal gastric electrical activity; both groups had baseline normal gastric activity while supine.48 

A study from the Mayo Clinic demonstrated that POTS symptoms in adolescents can improve with comprehensive interdisciplinary “pain rehabilitation,”49  though greater symptom burden positively correlated with delayed clinical improvement.10  However, some data suggest that POTS may be a comorbid finding not related to other symptoms (eg, fatigue, pain, dysmotility, headache, or joint hypermobility).50  Lastly, 14.2% of pediatric patients with POTS were found to have a family member with POTS, with 31.3% having a family member with orthostatic intolerance, 20.2% having a family member with joint hypermobility, and 45.1% having a family member with autoimmune disease.51 

Take-home points:

  • There are numerous medications that can be used to reduce symptoms of POTS.

  • Parenteral saline can be used to reduce symptoms as a temporizing measure but is typically not recommended as prolonged therapy.

There is a notable paucity of prospective data related to medication management of pediatric patients with POTS. In fact, the first double-blind, prospective, crossover trial of a medication in POTS in adults, ivabradine, was just published in 2021.52  The published studies addressing medication utilization in pediatric patients have been mostly retrospective and observational in nature, although there are a few small prospective studies. The 2 retrospective studies with the largest patient volumes were published by Boris et al.53,54  Both assessed effectiveness of various medication therapies for specific symptoms using a threshold of at least 5 medication refills of the same medication at the same dose consecutively as a proxy measure for efficacy. Although overall therapeutic efficacy for symptoms of lightheadedness, headache, nausea, dysmotility, pain, and insomnia ranged from 39% to 53%,53  efficacy for fatigue and cognitive dysfunction was greater, at nearly 70%.54  In both studies, the efficacy of multiple medications was assessed both individually, as well as within symptom groupings.

Other smaller studies have been performed in the pediatric population. A retrospective analysis of 27 patients demonstrated that ivabradine improved symptoms in 67% of patients,55  and another showed similar outcomes in 22 patients,56  both with minimal side effects. A meta-analysis was performed evaluating studies in which β blockers were used in pediatric patients with POTS.57  However, 7 of 8 studies reviewed were in Chinese and could not be assessed here. But the review stated that these 7 studies demonstrated significant concern for bias and were not considered to be of high enough quality. The eighth study, which was felt to be of adequate quality, was a prospective controlled study that was neither blinded nor randomized in evaluating groups receiving routine nonpharmacologic therapy, plus either a morning dose of 2.5 mg midodrine, twice daily metoprolol at 0.5 mg/kg per day, or no medications.58  Both midodrine and metoprolol therapy reduced symptom scores in children versus untreated patients, with midodrine leading to a higher rate of overall resolution of symptoms of orthostatic intolerance. Lin, who demonstrated elevated C-natriuretic peptide levels in the study mentioned previously, also showed in that same study that metoprolol lowered symptom scores in pediatric patients.35  Furthermore, a C-natriuretic peptide level greater than 32.55 pg/mL correlated with efficacy of metoprolol in lowering symptoms. Effectiveness of metoprolol was also assessed in a prospective trial, in which a threshold copeptin level of 10.225 pmol/L was predictive of efficacy.59  A retrospective chart review analysis and survey of adolescent patients suggested that patients treated with midodrine or with β blockers both reported clinical improvement with addition of medication therapy, although those using β blockade felt that their medication had a more significant role in symptom reduction.60  Lastly, in a prospective double-blind, placebo-controlled crossover study of midodrine in adolescents with neuropathic and hyperadrenergic POTS, midodrine was found to be effective in the treatment of those patients with neuropathic POTS, whereas no improvement or a placebo effect was seen in those with hyperadrenergic POTS.61 

In patients who fail oral medication therapy, parenteral therapy may be an option. The only study in children with this therapy is a retrospective study that uses intravenous normal saline in patients with POTS, neurally mediated hypotension, or orthostatic intolerance.62  Most patients reported an improved quality of life, although patients utilizing a permanent method of access, such as a peripherally inserted central catheter or central port, had a notable incidence of vascular thrombosis and infection.

Take-home points:

  • A thorough history evaluating associated symptoms, as well as for comorbid disorders, is key to ensuring a comprehensive therapeutic approach.

  • Except for clinical findings associated with comorbidities, physical examination findings may be completely normal.

  • Management starts with nonpharmacologic interventions, with addition of medications, as indicated.

The general pediatrician’s approach to the care of children and adolescents with POTS, as with any clinical concern, starts with the evaluation. A thorough history is necessary to assess for the wide array of symptoms associated with POTS9  (Fig 1), as well as symptoms seen in associated disorders, including but not limited to joint hypermobility syndromes,14  mast cell activation syndrome,63  craniocervical instability, median arcuate ligament syndrome,64  and autoimmune disorders such as Sjögren syndrome and systemic lupus erythematosus.65 

Physical examination findings can include manifestations of the above disorders, such as an elevated Beighton score, dermatographia, urticaria, an epigastric/abdominal bruit, venous pooling, dilated pupils, etc. Often, except for upright tachycardia, clinical examination may be normal. Initial studies should include a baseline electrocardiogram, plus consideration of 24-hour Holter monitoring evaluating for arrhythmias. Suggested laboratory investigations include morning cortisol, thyroid function testing, vitamin D level, and ferritin because derangements in these can lead to orthostatic intolerance.66 

Evaluation for orthostatic intolerance includes a 10-minute standing test. Ideally, continuous blood pressure and heart rate monitoring are performed, but measurements at least once per minute should be obtained. The patient should rest in the supine position for 5 minutes, with heart rate and blood pressure obtained at the conclusion. Then, the patient should immediately stand for 10 minutes, with minimal stimulation and movement. A persistent heart rate increase of ≥40 beats per minute without orthostatic hypotension (decreased blood pressure of 20 mmHg systolic or 10 mmHg diastolic) with symptoms of orthostatic intolerance, plus a history of symptoms for ≥3 months, is diagnostic for POTS (after ruling out other diagnoses), although some sites use a 30 beats per minute threshold. Although tilt testing is utilized in a number of formal autonomic laboratories, the majority of clinics do not have access to these.

In the absence of finding other treatable etiologies for symptoms, therapeutic management starts with nonpharmacologic intervention, which is foundational. Increasing intravascular volume with daily fluid intake of 80 to 120 ounces daily, plus 8 to 10 g of sodium chloride,8,67  is the most important initial treatment. Other therapies, including elevation of the head of the bed to reduce nocturnal diuresis,68  appropriate sleep hygiene, use of compression garments,69  and use of cooling vests to reduce heat intolerance are important adjunct measures. Initiation of an exercise protocol specifically for patients with POTS is important to help suppress symptoms. Fu and Levine developed a protocol utilizing initially recumbent aerobic exercises, plus isometric activities strengthening legs and core that produced important and lasting symptom reduction in adults with POTS.70,71  A version of their protocol modified for adolescents can be found online.72  However, basic principles of exercise for these patients include the following: utilizing both aerobic and isometric exercises, initially avoiding upright activities to prevent orthostatic intolerance, beginning with minimal duration of exercise, and ensuring consistent and progressive exercise. Patients with joint hypermobility are strongly advised to be evaluated by a physical therapist familiar with hypermobility to teach patients how to strengthen and protect their joints.73 

Often, nonpharmacologic therapy for POTS is insufficient to reduce symptoms, and patients are not able to resume their activities of daily living, much less incorporate exercise into their routine. Thus, use of medications to reduce symptoms of POTS can be beneficial. Although discussion of specific medication utilization is beyond the scope of this article, there are basic approaches that can be taken. One is to use medications targeted at specific symptoms.53,54  Another is to take a general approach to use of medications, aiming at supporting blood pressure, with use of therapies such as fludrocortisone or midodrine, while gently slowing heart rate to improve cardiac output, such as with β blockade or ivabradine.74  Many medications used in the management of POTS are already used in children and adolescents for medical disorders, allowing for familiarity. Certainly, these medications can have side effects, and patients may have persistent symptoms despite what seems to be appropriate therapy. Therefore, comfort using these medications takes practice, as well as communication with the patients and families. Patients may also require further referral to specialists, such as cardiologists, neurologists, gastroenterologists, allergist/immunologists, etc, depending upon specific persistent or abnormal clinical findings, or lack of response to therapy. In the United States, specialists in pediatric POTS include general pediatricians, pediatric cardiologists, pediatric gastroenterologists, and child neurologists. Caring for these patients and families is best achieved by providers with patience, perseverance, and creativity, and those who have time to validate, to explain details without using medical jargon, and to reassure these individuals.

Take-home points:

  • There is increasing research interest in pathophysiology and management of POTS.

  • Ensuring recognition of POTS in children and adolescents, including education and de-stigmatization, is important to allow patients to attain access to therapy.

Besides basic questions of underlying POTS pathophysiology, evaluation, and therapy, numerous questions pertaining to these patients remain, including whether pediatric POTS occurs with minimal symptoms, ascertainment of appropriate criteria for diagnosis (including orthostatic testing and heart rate cutoffs), how growth and hormonal changes influence POTS, roles of maladaptive psychiatric health of patients and parents, determination if POTS is 1 disease entity or multiple entities, the role of genetics, and the function of the immune response and inflammation on pathophysiology. These unanswered questions continue to limit the ability to more consistently diagnose and manage this diverse group of patients. As the adage “Children are not just small adults” rings true, so does another oft-repeated statement in multiple journal articles: “More research is required.” The NIH recently issued a notice of special interest to stimulate research on diagnosis, treatment, and mechanistic understanding of POTS.75  As well, starting in 2021, the NIH listed funding for POTS in their annual categorical spending,76  so that the amount of research dollars spent on this disorder can be better followed.

Yet, even basic recognition of POTS in adolescents remains limited. Diagnosis is typically delayed by a median of >3 years, especially with comorbid joint hypermobility.9  Patients may be recognized as having something wrong without ability of the provider to give further guidance,1  or are incorrectly diagnosed as having a psychological or psychiatric disorder.1 

As knowledge and interest in this disorder, as well as research, continues to increase, the relative volume of pediatric research will also rise. Recognition of the unique aspects of pediatric POTS, specifically, will further augment greater understanding of this syndrome in general. But most importantly, improving understanding of pediatric and adolescent providers about its presence and diagnostic criteria will allow patients to receive a diagnosis and to access the care that they require to be able to return to their daily lives.

Drs Boris and Moak conceptualized this review article, drafted the initial manuscript, and reviewed and revised the manuscript; and both authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Postural orthostatic tachycardia syndrome, a poorly understood and recognized diagnosis, has had limited pediatric research. This article reviews existing data and discusses future research approaches.

FUNDING: No external funding.

     
  • GI

    gastrointestinal

  •  
  • NIH

    National Institutes of Health

  •  
  • POTS

    postural orthostatic tachycardia syndrome

1
Shaw
BH
,
Stiles
LE
,
Bourne
K
, et al
.
The face of postural tachycardia syndrome: insights from a large cross-sectional online community-based survey
.
J Intern Med
.
2019
;
286
(
4
):
438
448
2
Bourne
KM
,
Chew
DS
,
Stiles
LE
, et al
.
Postural orthostatic tachycardia syndrome is associated with significant employment and economic loss
.
J Intern Med
.
2021
;
290
(
1
):
203
212
3
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
4
National Center for Biotechnology Information
.
PubMed
.
Available at: www.pubmed.gov. Accessed September 5, 2021
5
Collins
FS
.
Department of Health and Human Services
;
National Institutes of Health
;
National Heart, Lung, and Blood Institute
;
National Institute of Neurological Disorders and Stroke
.
Postural orthostatic tachycardia syndrome (POTS): state of the science, clinical care, and research
.
6
Vernino
S
,
Bourne
KM
,
Stiles
LE
, et al
.
Postural orthostatic tachycardia syndrome (POTS): state of the science and clinical care from a 2019 National Institutes of Health expert consensus meeting - part 1
.
Auton Neurosci
.
2021
;
235
:
102828
7
Raj
SR
,
Bourne
KM
,
Stiles
LE
, et al
.
Postural orthostatic tachycardia syndrome (POTS): priorities for POTS care and research from a 2019 National Institutes of Health expert consensus meeting - part 2
.
Auton Neurosci
.
2021
;
235
:
102836
8
Stewart
JM
,
Boris
JR
,
Chelimsky
G
, et al.
Pediatric Writing Group of the American Autonomic Society
.
Pediatric disorders of orthostatic intolerance
.
Pediatrics
.
2018
;
141
(
1
):
e20171673
9
Boris
JR
,
Bernadzikowski
T
.
Demographics of a large paediatric postural orthostatic tachycardia syndrome program
.
Cardiol Young
.
2018
;
28
(
5
):
668
674
10
Li
J
,
Zhang
Q
,
Hao
H
,
Jin
H
,
Du
J
.
Clinical features and management of postural tachycardia syndrome in children: a single-center experience
.
Chin Med J (Engl)
.
2014
;
127
(
21
):
3684
3689
11
Heyer
GL
,
Fischer
A
,
Wilson
J
, et al
.
Orthostatic intolerance and autonomic dysfunction in youth with persistent postconcussion symptoms: a head-upright tilt table study
.
Clin J Sport Med
.
2016
;
26
(
1
):
40
45
12
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
13
Boris
JR
,
Huang
J
,
Bernadzikowski
T
.
Orthostatic heart rate does not predict symptomatic burden in pediatric patients with chronic orthostatic intolerance
.
Clin Auton Res
.
2020
;
30
(
1
):
19
28
14
Boris
JR
,
Bernadzikowski
T
.
Prevalence of joint hypermobility syndromes in pediatric postural orthostatic tachycardia syndrome
.
Auton Neurosci
.
2021
;
231
:
102770
15
Sheldon
RS
,
Grubb
BP
II
,
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
16
Plash
WB
,
Diedrich
A
,
Biaggioni
I
, et al
.
Diagnosing postural tachycardia syndrome: comparison of tilt testing compared with standing haemodynamics
.
Clin Sci (Lond)
.
2013
;
124
(
2
):
109
114
17
Medow
MS
,
Merchant
S
,
Suggs
M
,
Terilli
C
,
O’Donnell-Smith
B
,
Stewart
JM
.
Postural heart rate changes in young patients with vasovagal syncope
.
Pediatrics
.
2017
;
139
(
4
):
e20163189
18
Shen
WK
,
Sheldon
RS
,
Benditt
DG
, et al
.
2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the heart rhythm society
.
Circulation
.
2017
;
136
(
5
):
e60
e122
19
Johnson
JN
,
Mack
KJ
,
Kuntz
NL
,
Brands
CK
,
Porter
CJ
,
Fischer
PR
.
Postural orthostatic tachycardia syndrome: a clinical review
.
Pediatr Neurol
.
2010
;
42
(
2
):
77
85
20
Boris
JR
,
McClain
ZBR
,
Bernadzikowski
T
.
Clinical course of transgender adolescents with complicated postural orthostatic tachycardia syndrome undergoing hormonal therapy in gender transition: a case series
.
Transgend Health
.
2019
;
4
(
1
):
331
334
21
Blitshteyn
S
.
Postural tachycardia syndrome following human papillomavirus vaccination
.
Eur J Neurol
.
2014
;
21
(
1
):
135
139
22
Pharmacovigilance Risk Assessment Committee
.
Human Papillomavirus (HPV) Vaccines
.
London
:
European Medicines Agency
;
2015
23
Skufca
J
,
Ollgren
J
,
Ruokokoski
E
,
Lyytikäinen
O
,
Nohynek
H
.
Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012
.
Papillomavirus Res
.
2017
;
3
:
91
96
24
Schenkel
LC
,
Singh
RK
,
Michel
V
, et al
.
Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts
.
FASEB J
.
2015
;
29
(
5
):
1663
1675
25
Bhatia
R
,
Kizilbash
SJ
,
Ahrens
SP
, et al
.
Outcomes of adolescent-onset postural orthostatic tachycardia syndrome
.
J Pediatr
.
2016
;
173
:
149
153
26
Tao
C
,
Lu
W
,
Lin
J
, et al
.
Long-term outcomes of children and adolescents with postural tachycardia syndrome after conventional treatment
.
Front Pediatr
.
2019
;
7
:
261
27
Kizilbash
SJ
,
Ahrens
SP
,
Bruce
BK
, et al
.
Adolescent fatigue, POTS, and recovery: a guide for clinicians
.
Curr Probl Pediatr Adolesc Health Care
.
2014
;
44
(
5
):
108
133
28
Frey
S
,
Balu
S
,
Greusing
S
,
Rothen
N
,
Cajochen
C
.
Consequences of the timing of menarche on female adolescent sleep phase preference
.
PLoS One
.
2009
;
4
(
4
):
e5217
29
Padilla-Walker
LM
,
Nelson
LJ
.
Black Hawk down? Establishing helicopter parenting as a distinct construct from other forms of parental control during emerging adulthood
.
J Adolesc
.
2012
;
35
(
5
):
1177
1190
30
Boris
JR
.
Postural orthostatic tachycardia syndrome in children and adolescents
.
Auton Neurosci
.
2018
;
215
:
97
101
31
Liao
Y
,
Chen
S
,
Liu
X
, et al
.
Flow-mediated vasodilation and endothelium function in children with postural orthostatic tachycardia syndrome
.
Am J Cardiol
.
2010
;
106
(
3
):
378
382
32
Zhang
F
,
Li
X
,
Stella
C
, et al
.
Plasma hydrogen sulfide in differential diagnosis between vasovagal syncope and postural orthostatic tachycardia syndrome in children
.
J Pediatr
.
2012
;
160
(
2
):
227
231
33
Stewart
JM
,
Weldon
A
.
The relation between lower limb pooling and blood flow during orthostasis in the postural orthostatic tachycardia syndrome of adolescents
.
J Pediatr
.
2001
;
138
(
4
):
512
519
34
Li
H
,
Han
Z
,
Chen
S
, et al
.
Total peripheral vascular resistance, cardiac output, and plasma C-type natriuretic peptide level in children with postural tachycardia syndrome
.
J Pediatr
.
2015
;
166
(
6
):
1385
9.e1
,
2
35
Lin
J
,
Han
Z
,
Li
H
, et al
.
Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome
.
PLoS One
.
2015
;
10
(
3
):
e0121913
36
Bai
W
,
Han
Z
,
Chen
S
, et al
.
Serum resistin negatively correlates with clinical severity of postural tachycardia syndrome in children
.
Pediatr Cardiol
.
2017
;
38
(
8
):
1639
1644
37
Xu
WR
,
Jin
HF
,
Du
JB
.
Pathogenesis and individualized treatment for postural tachycardia syndrome in children
.
Chin Med J (Engl)
.
2016
;
129
(
18
):
2241
2245
38
Zhao
J
,
Yang
J
,
Du
S
,
Tang
C
,
Du
J
,
Jin
H
.
Changes of atrial natriuretic peptide and antidiuretic hormone in children with postural tachycardia syndrome and orthostatic hypertension: a case control study
.
Chin Med J (Engl)
.
2014
;
127
(
10
):
1853
1857
39
Zhang
Q
,
Liao
Y
,
Tang
C
,
Du
J
,
Jin
H
.
Twenty-four-hour urinary sodium excretion and postural orthostatic tachycardia syndrome
.
J Pediatr
.
2012
;
161
(
2
):
281
284
40
Stewart
JM
,
Medow
MS
,
Glover
JL
,
Montgomery
LD
.
Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome
.
Am J Physiol Heart Circ Physiol
.
2006
;
290
(
2
):
H665
H673
41
Stewart
JM
,
Kota
A
,
O'Donnell-Smith
MB
,
Visintainer
P
,
Terilli
C
,
Medow
MS
.
The preponderance of initial orthostatic hypotension in postural tachycardia syndrome
.
J Appl Physiol (1985)
.
2020
;
129
(
3
):
459
466
42
Lu
W
,
Yan
H
,
Wu
S
, et al
.
Electrocardiography-derived predictors for therapeutic response to treatment in children with postural tachycardia syndrome
.
J Pediatr
.
2016
;
176
:
128
133
43
Cai
H
,
Wang
S
,
Zou
R
,
Wang
Y
,
Wang
C
.
Circadian rhythms of blood pressure and rate pressure product in children with postural tachycardia syndrome
.
Auton Neurosci
.
2020
;
228
:
102715
44
Cai
H
,
Wang
S
,
Zou
R
, et al
.
Diagnostic value of diurnal variability of orthostatic heart rate increment in children and adolescents with POTS
.
Front Pediatr
.
2021
;
9
:
644461
45
Heyer
GL
,
Fedak
EM
,
LeGros
AL
.
Symptoms predictive of postural tachycardia syndrome (POTS) in the adolescent headache patient
.
Headache
.
2013
;
53
(
6
):
947
953
46
Zhang
LN
,
Moak
JP
,
Desbiens
J
, et al
.
Utility of diagnostic studies for upper gastrointestinal symptoms in children with orthostatic intolerance
.
J Pediatr
.
2019
;
205
:
138
144
47
Manini
ML
,
Barazi
A
,
Khemani
D
, et al
.
Gastrointestinal motility evaluation in children with orthostatic intolerance: Mayo Clinic experience
.
Neurogastroenterol Motil
.
2020
;
32
(
8
):
e13863
48
Safder
S
,
Chelimsky
TC
,
O’Riordan
MA
,
Chelimsky
G
.
Gastric electrical activity becomes abnormal in the upright position in patients with postural tachycardia syndrome
.
J Pediatr Gastroenterol Nutr
.
2010
;
51
(
3
):
314
318
49
Bruce
BK
,
Weiss
KE
,
Ale
CM
,
Harrison
TE
,
Fischer
PR
.
Development of an interdisciplinary pediatric pain rehabilitation program: the first 1000 consecutive patients
.
Mayo Clin Proc Innov Qual Outcomes
.
2017
;
1
(
2
):
141
149
50
Chelimsky
G
,
Kovacic
K
,
Nugent
M
,
Mueller
A
,
Simpson
P
,
Chelimsky
TC
.
Comorbid conditions do not differ in children and young adults with functional disorders with or without postural tachycardia syndrome
.
J Pediatr
.
2015
;
167
(
1
):
120
124
51
Boris
JR
,
Huang
J
,
Shuey
T
,
Bernadzikowski
T
.
Family history of associated disorders in patients with postural tachycardia syndrome
.
Cardiol Young
.
2020
;
30
(
3
):
388
394
52
Taub
PR
,
Zadourian
A
,
Lo
HC
,
Ormiston
CK
,
Golshan
S
,
Hsu
JC
.
Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome
.
J Am Coll Cardiol
.
2021
;
77
(
7
):
861
871
53
Boris
JR
,
Bernadzikowski
T
.
Utilization of medications to reduce symptoms in children with postural orthostatic tachycardia syndrome
.
Cardiol Young
.
2018
;
28
(
12
):
1386
1392
54
Boris
JR
,
Bernadzikowski
T
.
Therapy for fatigue and cognitive dysfunction in postural orthostatic tachycardia syndrome
.
Cardiol Young
.
2018
;
28
(
12
):
1415
1420
55
Towheed
A
,
Nesheiwat
Z
,
Mangi
MA
,
Karabin
B
,
Grubb
BP
.
Ivabradine in children with postural orthostatic tachycardia syndrome: a retrospective study
.
Cardiol Young
.
2020
;
30
(
7
):
975
979
56
Delle Donne
G
,
Rosés Noguer
F
,
Till
J
,
Salukhe
T
,
Prasad
SK
,
Daubeney
PEF
.
Ivabradine in postural orthostatic tachycardia syndrome: preliminary experience in children
.
Am J Cardiovasc Drugs
.
2018
;
18
(
1
):
59
63
57
Deng
X
,
Zhang
Y
,
Liao
Y
,
Du
J
.
Efficacy of β-blockers on postural tachycardia syndrome in children and adolescents: a systematic review and meta-analysis
.
Front Pediatr
.
2019
;
7
:
460
58
Chen
L
,
Wang
L
,
Sun
J
, et al
.
Midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syndrome
.
Circ J
.
2011
;
75
(
4
):
927
931
59
Zhao
J
,
Du
S
,
Yang
J
, et al
.
Usefulness of plasma copeptin as a biomarker to predict the therapeutic effectiveness of metoprolol for postural tachycardia syndrome in children
.
Am J Cardiol
.
2014
;
114
(
4
):
601
605
60
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
61
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
62
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
63
Shibao
C
,
Arzubiaga
C
,
Roberts
LJ
II
, et al
.
Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders
.
Hypertension
.
2005
;
45
(
3
):
385
390
64
Moak
JP
,
Ramwell
C
,
Fabian
R
,
Hanumanthaiah
S
,
Darbari
A
,
Kane
TD
.
Median arcuate ligament syndrome with orthostatic intolerance: intermediate-term outcomes following surgical intervention
.
J Pediatr
.
2021
;
231
:
141
147
65
Goodman
BP
,
Crepeau
A
,
Dhawan
PS
,
Khoury
JA
,
Harris
LA
.
Spectrum of autonomic nervous system impairment in Sjögren syndrome
.
Neurologist
.
2017
;
22
(
4
):
127
130
66
Antiel
RM
,
Caudill
JS
,
Burkhardt
BE
,
Brands
CK
,
Fischer
PR
.
Iron insufficiency and hypovitaminosis D in adolescents with chronic fatigue and orthostatic intolerance
.
South Med J
.
2011
;
104
(
8
):
609
611
67
Medow
MS
,
Guber
K
,
Chokshi
S
,
Terilli
C
,
Visintainer
P
,
Stewart
JM
.
The benefits of oral rehydration on orthostatic intolerance in children with postural tachycardia syndrome
.
J Pediatr
.
2019
;
214
:
96
102
68
Cooper
VL
,
Hainsworth
R
.
Head-up sleeping improves orthostatic tolerance in patients with syncope
.
Clin Auton Res
.
2008
;
18
(
6
):
318
324
69
Bourne
KM
,
Sheldon
RS
,
Hall
J
, et al
.
Compression garment reduces orthostatic tachycardia and symptoms in patients with postural orthostatic tachycardia syndrome
.
J Am Coll Cardiol
.
2021
;
77
(
3
):
285
296
70
Shibata
S
,
Fu
Q
,
Bivens
TB
,
Hastings
JL
,
Wang
W
,
Levine
BD
.
Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome
.
J Physiol
.
2012
;
590
(
15
):
3495
3505
71
Fu
Q
,
Levine
BD
.
Exercise in the postural orthostatic tachycardia syndrome
.
Auton Neurosci
.
2015
;
188
:
86
89
72
Instructions for POTS exercise protocol
.
73
Miranda
NA
,
Boris
JR
,
Kouvel
KM
,
Stiles
L
.
Activity and exercise intolerance after concussion: identification and management of postural orthostatic tachycardia syndrome
.
J Neurol Phys Ther
.
2018
;
42
(
3
):
163
171
74
Y Lei
L
,
S Chew
D
,
K Sandhu
R
,
S Sheldon
R
,
R Raj
S
.
Non-pharmacological and pharmacological management of cardiac dysautonomia syndromes
.
J Atr Fibrillation
.
2020
;
13
(
1
):
2395
75
Notice of special interest (NOSI): stimulate research on the diagnosis, treatment, and mechanistic understanding of postural orthostatic tachycardia syndrome (POTS)
.
76
Estimates of funding for various research, condition, and disease categories (RCDC)
.
Available at: https://report.nih.gov/funding/categorical-spending#/. Accessed Sept. 29, 2021

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.