Postural Tachycardia Syndrome: A Concise and Practical Guide to Management and Associated Conditions

This book describes the varying clinical manifestations of postural tachycardia syndrome (PoTS) and provides a robust yet practical set of clinical tools for those managing patients suffering with this syndrome. Guidance is provided by a range of disciplines relevant to PoTS including general and specialist assessments, associated conditions, diagnostic considerations, therapy and service models. 

Postural Tachycardia Syndrome: A Concise and Practical Guide to Management and Associated Conditions presents the scientific background and practical information for the busy medical professional, illustrating key features with care-based materials to help them manage this condition, which can be a challenge for patients and clinicians alike.

• Language: English
• Publisher: Springer
• Release date: Oct 21, 2020
• ISBN: 9783030541651

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© Springer Nature Switzerland AG 2021

N. Gall et al. (eds.)Postural Tachycardia Syndromehttps://doi.org/10.1007/978-3-030-54165-1_3

Clinical Presentation

Nicholas Gall¹  

(1)

Department of Cardiology, King’s College Hospital, London, SE5 9RS, UK

Nicholas Gall

Email: [e-mail]

Keywords

Postural tachycardiaPre-syncopeSyncopeChest painBreathlessnessPalpitation

Postural tachycardia syndrome, as a syndrome, is defined as a collection of symptoms present for at least six months associated with cardiovascular abnormalities on standing, where the heart rate increases inappropriately and remains persistently raised without significant orthostatic hypotension [1–3]. The details of securing the diagnosis are to be found in other chapters of this text. While the clinical definition relies on a significant heart rate change, that heart rate change can vary both with the time of day [4, 5], whether the patient has eaten recently and in women with relation to the menstrual cycle [6]. There are no other specific laboratory / imaging markers for this condition and indeed it is described as a syndrome and therefore, as detailed elsewhere, it may well represent a number of different pathophysiologies. In light of that, the diagnosis should rest not only on suggestive physiological findings but also on the clinical presentation of the patient. Review articles have been published in the field, detailing the clinical presentation in major centres [7] and other organisations have also assessed patients with the condition in an effort to understand their symptoms [8, 9].

There is no true understanding of the prevalence of the condition, although 170/100,000 population is often quoted although that is an estimate based on an assumption that 40% of patients with chronic fatigue syndrome have PoTS [10]. This may mean that from 500,000 to 3,000,000 Americans are affected [2]. No UK study to date has assessed the incidence or prevalence in any formalised manner but many clinicians believe that it is likely to be more common than is often perceived. The condition is particularly common in younger women and usually presents between the ages of 15 and 25 although patients will often describe that their symptoms began earlier and indeed a recent review of patient symptoms suggests that the modal age of onset is 14 [8]. It seems to be at least three times more common in women for which there are potential explanations, detailed elsewhere. It is important to recognise this demographic as clearly, while other patients may present with PoTS-like symptoms, the more different the patient is from this classical demographic the more one needs to be concerned that there may be an alternative explanation, perhaps a more significant underlying autonomic disturbance. In some cases, patients will describe their cardiovascular symptoms as being present for as long as they can remember and from personal experience, this may be more likely in those with hypermobility. One quarter may have a family history of similar complaints [11].

In many other cases, there is a sudden onset to the symptoms, in association with another illness [10]. Often this may be a viral illness, for instance glandular fever (Epstein Barr virus); however many other precipitants can be associated, for instance a road traffic accident, during a pregnancy or after a complicated labour, after an operation or a vaccination. Stressful events may also be noted as a precipitant although, as detailed elsewhere, this should not be taken to suggest that the condition is purely psychological. In the end, it does not appear that one particular event precipitates PoTS, it is often a significant event potentially putting strain on the system which produces the changes. While deconditioning may be relevant to many symptoms, as will be detailed elsewhere, the sudden onset in many cases would suggest that deconditioning is not the specific driver in most cases, more often a contributor, albeit important.

PoTS tends to present with a multitude of symptoms affecting many different organ systems but is particularly focused on the cardiovascular system and it is for that reason that many patients with this condition will be seen in cardiology clinics. The table below details the frequency of these symptoms in two reviews (Table 1).

Table 1

The symptoms associated with PoTS have been studied in a number of series; detailed here is a summary of findings from the Mayo clinic and a more recent patient questionnaire

The most frequently quoted study of patient symptoms originates from the Mayo clinic. Thieban and colleagues [7] documented their experience over an 11-year period. They included patients with the classical definition of PoTS and excluded patients with orthostatic hypotension, pregnancy, other causes of autonomic failure and those with systemic illness. They identified 152 patients, 87% being female, with symptoms predating the diagnosis by an average of four years. One in eight had a family history of orthostatic intolerance and 40% had a prior history to some degree. 13% had symptoms beginning acutely within one month, 14% between one and three months and 6% with a more gradual onset over three months or more, although in two thirds the onset was not defined. In their series, one quarter felt that there was a precipitant, often a viral illness but the majority did not recognise a clear cause. They noted a wide range of symptoms, many relating to cardiovascular symptoms but other, non-orthostatic symptoms and more general symptoms were also notable. Symptoms were noted to worsen in over half of patients with exercise or heat, a quarter noted worsening around a meal and 15% around the time of their period.

Shaw and colleagues [8] have more recently summarised the characteristics of PoTS patients with a large, cross-sectional, online community-based survey, conducted between academic institutions and Dysautonomia International, a USA-based patient advocacy organisation. There will clearly be some limitation as the data originates from self-reported diagnosis and symptoms but is a much larger sample, involving 4835 participants. The mean age of symptom onset in their cohort was 21 (±12) years with a median of 17 and a modal age of onset at 14. Nearly 50% noted their symptoms began after the age of 18. 41% of patients reported that their symptoms had started within three months of a particular event, in particular an infection in 41%, after surgery in 12%, with a pregnancy in 9%, after a vaccination in 6%, after an accident in 6%, with puberty in 5%, after a concussion in 4% or with an emotional stress/trauma in 3%. In this self-selected group, 94% of patients were female. A median of 24 months for diagnosis from symptom onset was notable. 16% of patients had some form of autoimmune disease.

A survey of PoTS patients based in the UK derived from the Newcastle PoTS clinic and subscribing to the PoTS-UK charity [9], assessed 136 patients with a mean age of 33, 10% of whom were male. On average, their symptoms began at 24 years of age but were diagnosed at 31 suggesting that diagnosis may take up to 7 years in many cases. They noted significant associated conditions including 21% diagnosed with chronic fatigue syndrome, 18% diagnosed with EDS/hypermobility, 10% with irritable bowel syndrome, 10% with thyroid problems and 7% with fibromyalgia. They also noted that 43% of PoTS patients who had not been diagnosed with chronic fatigue syndrome would in fact have fulfilled criteria for that condition.

The most common symptoms relate to a sense of faintness, particularly associated with standing, not only when patients stand initially (initial orthostatic hypotension), but also when patients stand for any length of time. Patients will often feel that they have a sense that they need to sit or lie down in those situations to avoid losing consciousness. As will be detailed later, there is also an association with more vertiginous dizziness where patients may fear that they will fall from being off-balance which does need to be differentiated from these feelings of faintness. While PoTS patients are at risk of losing consciousness with a vasovagal mechanism, this is perhaps less common than might be assumed, perhaps 30% [6]. There is also a distinct association with dissociative syncope in this condition. From personal experience, although the exact reasons for that remain uncertain, this will also produce an apparent loss of consciousness. However, these two forms of collapse can be differentiated. Vasovagal syncope is usually associated with autonomic symptoms and a rapid recovery of consciousness albeit with patients feeling generally unwell and washed out afterwards, whereas dissociative syncope [12] may happen more frequently (many times a day), may be more prolonged (minutes and even longer), may be associated with atypical seizure-like movements and may be associated with eye closure which is not something that occurs with vasovagal syncope.

Many PoTS patients complain of chest pain although there is very little understanding of the exact aetiology [6]. It can take a number of different forms including sharp, stabbing pains which may be more musculoskeletal, and may potentially link in with hypermobility. There can be associations with gastrointestinal disturbance, as will be detailed later, which can also precipitate chest pain of a more oesophageal quality. A number of patients describe angina-like chest tightness, which may associate with their sinus tachycardia. ECG changes in the inferior leads may occur [6]. The exact aetiology is uncertain, but this may also associate with dysfunctional breathing which is recognised to associate with PoTS (see Chapter 39 and Physiotherapy intervention for Patients with PoTS Presenting with Breathlessness). Dysfunctional breathing will also produce breathlessness on exertion, where patients will feel that their exercise abilities are limited. However, it may not associate with other respiratory symptoms, may be described as ‘air hunger’ and may associate with either gasping or yawning respiration, potentially with hand or facial paraesthesiae. This can also occur when patients are lying flat in bed but is different to orthopnoea in character. Patients may note some ankle swelling, but often they also tend to report red or purple discolouration of their legs when dependent (acrocyanosis), which is often described as pooling, although this may represent skin ischaemia [2, 13].

Patients often describe palpitation, some of which will relate to sensing ectopic beats as flutters, pauses, missed or extra beats. However, it does not appear that PoTS patients suffer any more ectopic beats than any other patient, although they do seem to be more aware of those symptoms. Their sinus rate is often inappropriately fast and therefore much of the palpitation will relate to a sense that their heart is beating harder, more strongly and faster than is required for the circumstances. It may be that this is noted suddenly. However usually this form of palpitation passes off gradually, therefore differentiating it from other arrhythmias such as supraventricular tachycardia (SVT).

Differing forms of PoTS have been recognised by some, for instance neuropathic and hyperadrenergic. They may present with differing symptoms; hyperadrenergic PoTS may be more likely to present with palpitation, anxiety, tachycardia and tremor [10]. Kanjwal in the Cardiology Journal in 2011 [14] also describe their experience with this form. They felt that in their series, these patients had a more gradual onset of symptoms in comparison to others. They also note complaints of feeling cold and sweaty when upright and also note migraine in more than half. They also found that one third of their patients had high blood pressure. Differentiating these two distinct forms, if they exist, may however be not so clear-cut from personal experience.

With the associated features and conditions, which are detailed elsewhere in this text, it is well-recognised that PoTS patients also describe symptoms in other organ territories although these can vary from patient to patient. They may present with gastrointestinal symptoms, urological symptoms, migraines, joint symptoms perhaps associating with hypermobility [15] and allergic symptoms associating with potential mast cell activation. In many patients, more vertiginous dizziness is often described which seems in many to link in with vestibular migraine. There can be a significant association with fatigue although there is little true understanding as to the exact causes of fatigue and it is for that reason that there is an overlap with chronic fatigue syndrome. Garland et al. [2] note that chronic fatigue may affect 48–77% of PoTS patients with 17–23% of patients being diagnosed formally with chronic fatigue syndrome.

Many patients complain of cold hands and feet, often with features of Raynaud’s and poor temperature control, that is persistently feeling the wrong temperature for the environment; again, the reasons for these symptoms remain uncertain. Grubb and colleagues [16] note in addition significant functional impairment similar to patients with chronic obstructive pulmonary disease or heart failure.

In light of the widespread and disparate symptoms associated with this condition, many patients will present to a number of different physicians, potentially over a number of months and even years and indeed studies would suggest that many patients may take years prior to their receiving a diagnosis, having seen multiple different physicians in the interim [8, 9]. In many cases, the large number of symptoms associated can cause confusion in clinicians who are not aware of this problem and may consider that there can be little physiological basis to these multitudinous symptoms. Abnormalities in the autonomic nervous system, of course, can provide a clear explanation for the widespread issues.

The diagnosis of PoTS therefore rests not only on the suggestive findings of a significant heart rate change on a stand test but also the presentation in a patient of the correct age, beginning in a classical manner, without an alternative explanation. The response to medications, which will be detailed elsewhere and indeed lifestyle change, will also provide support for the diagnosis. Clinicians in the field no longer focus to such an extent on the absolute heart rate change, an acknowledgment of the complexity of the presentation which is reflected in the Canadian Cardiac Society guidance [17].

References

1.

2015 Heart rhythm society expert consensus statement on the diagnosis and treatment of postural Tachycardia syndrome, inappropriate sinus Tachycardia, and Vasovagal syncope. Heart Rhythm Soc [Internet] [cited 2019 Nov 27]. https://​www.​hrsonline.​org/​clinical-resources/​2015-heart-rhythm-society-expert-consensus-statement-diagnosis-and-treatment-postural-tachycardia.

2.

Garland EM, Celedonio JE, Raj SR. Postural Tachycardia syndrome: beyond orthostatic intolerance. In: Current neurology and neuroscience reports, vol. 15. Current Medicine Group LLC 1; 2015.

3.

Carew S, Connor MO, Cooke J, Conway R, Sheehy C, Costelloe A, et al. A review of postural orthostatic tachycardia syndrome. Europace. 2009;11:18–25.

4.

Plash WB, Diedrich A, Biaggioni I, Garland EM, Paranjape SY, Black BK, et al. Diagnosing postural tachycardia syndrome: Comparison of tilt testing compared with standing haemodynamics. Clin Sci [Internet]. 2013 [cited 2020 Jan 12];124(2):109–14. https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​22931296.

5.

Nwazue VC, Arnold AC, Raj V, Black BK, Biaggioni I, Paranjape SY, et al. Understanding the placebo effect in clinical trials for postural tachycardia syndrome. Clin Exp Pharmacol Physiol. 2014;41(5):325–30.Crossref

6.

Raj SR. Postural tachycardia syndrome (POTS). Circulation. 2013;127(23):2336–42.Crossref

7.

Thieben MJ, Sandroni P, Sletten DM, Benrud-Larson LM, Fealey RD, Vernino S, et al. Postural orthostatic tachycardia syndrome: the Mayo clinic experience. Mayo Clin Proc [Internet]. 2007 [cited 2020 Jan 12];82(3):308–13. https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​17352367.

8.

Shaw BH, Stiles LE, Bourne K, Green EA, Shibao CA, Okamoto LE, et al. The face of postural tachycardia syndrome—insights from a large cross-sectional online community-based survey. J Intern Med. 2019;286(4):438–48.Crossref

9.

McDonald C, Koshi S, Busner L, Kavi L, Newton JL. Postural tachycardia syndrome is associated with significant symptoms and functional impairment predominantly affecting young women: a UK perspective. BMJ Open. 2014;4(6).

10.

Low PA, Sandroni P, Joyner M, Shen WK. Postural tachycardia syndrome (POTS): clinical review. J Cardiovasc Electrophysiol. 2009;20:352–8.

11.

Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. In: Mayo clinic proceedings, vol. 87. Elsevier Ltd; 2012. p. 1214–25.

12.

Blad H, Lamberts RJ, Dijk JG Van, Thijs RD. Tilt-induced vasovagal syncope and psychogenic pseudosyncope. Neurology. 2015;85(23):2006–10.

13.

Medow MS, Stewart JM. The postural tachycardia syndrome. Cardiol Rev. 2007;15:67–75.

14.

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 [Internet]. 2011 [cited 2020 Jan 12];18(5):527–31. https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​21947988.

15.

Mathias CJ, Low DA, Iodice V, Owens AP, Kirbis M, Grahame R. Postural tachycardia syndrome—current experience and concepts. Nat Rev Neurol. 2012;8:22–34.

16.

Grubb BP, Kanjwal Y, Kosinski DJ. The postural tachycardia syndrome: a concise guide to diagnosis and management. J Cardiovasc Electrophysiol. 2006;17(1):108–12.PubMed

17.

Raj SR, Guzman JC, Harvey P, et al. Canadian Cardiovascular Society Position Statement on Postural Orthostatic Tachycardia Syndrome (POTS) and Related Disorders of Chronic Orthostatic Intolerance. Can J Cardiol. 2020; 36(3):357–72. https://​doi.​org/​10.​1016/​j.​cjca.​2019.​12.​024.

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© Springer Nature Switzerland AG 2021

N. Gall et al. (eds.)Postural Tachycardia Syndromehttps://doi.org/10.1007/978-3-030-54165-1_4

Diagnostic Criteria for Postural Tachycardia Syndrome: Consideration of the Clinical Features Differentiating PoTS from Other Disorders of Orthostatic Intolerance

Kate M. Bourne¹, Matthew G. Lloyd¹ and Satish R. Raj¹, ²  

(1)

University of Calgary, Calgary, AB, Canada

(2)

Vanderbilt University Medical Center, Nashville, TN, USA

Satish R. Raj

Email: [e-mail]

Keywords

PoTSOrthostatic tachycardiaOrthostatic intolerancePostural tachycardia syndromeOrthostatic tachycardia

Abbreviations

ADHD

Attention deficit hyperactivity disorder

HR

Heart Rate

IOH

Initial Orthostatic Hypotension

IST

Inappropriate Sinus Tachycardia

OH

Orthostatic Hypotension

PoTS

Postural Tachycardia Syndrome

NET

Norepinephrine transporter

SNRI

Serotonin-norepinephrine reuptake inhibitor

Background

The current definition of Postural Tachycardia Syndrome (PoTS) was developed in 1993 by Ron Schondorf and Phillip Low in an effort to provide a standardized profile for this disorder [1]. Prior to this, accounts of PoTS in the literature only referred to small or single sample cases [1]. Through reviewing a set of patients age 20–51 years who demonstrated orthostatic tachycardia during testing at the Mayo Autonomic Reflex Laboratory, a PoTS diagnosis was made if the heart rate (HR) increase was 2 standard deviations above the mean increase for a sex-matched control population [1]. Importantly, these data excluded children and adolescents.

Diagnostic Criteria

PoTS is a chronic form of orthostatic intolerance marked by excessive orthostatic tachycardia and associated symptoms. Specifically, a PoTS diagnosis is made when, upon assumption of upright posture, a sustained HR increase of 30 beats per minute (bpm) or more is observed in association with symptoms of orthostatic intolerance [2, 3]. In youth under 19 years of age, this HR increase should be 40 bpm or more. Diagnosing PoTS in pediatric patients will be discussed later in this chapter. The duration of the increased HR should be sustained – in other words, seen on at least 2 consecutive recordings. This orthostatic tachycardia should develop within 10 minutes of upright posture [2]. It is not unusual, but not necessary for diagnosis, for the HR to exceed 120 bpm [2, 3]. Orthostatic symptoms should improve with recumbence, and may include lightheadedness, blurry vision, tremulousness, and weakness [2, 3]. The observed postural tachycardia should also be in the absence of orthostatic hypotension (>20/10 mmHg decrease in blood pressure [BP]) [3], and symptoms should be chronic (lasting at least 3–6 months) [4]. The critical concern is that PoTS patients must have both excessive orthostatic tachycardia and symptoms of orthostatic intolerance in order to meet the criteria for this disorder. The diagnostic criteria are summarized in Table 1.

Table 1

PoTS diagnostic criteria

Clinical Evaluation of a Patient with Suspected PoTS

While seemingly simple, there are many caveats to the PoTS diagnosis that are important when differentiating between this disorder and other causes of orthostatic intolerance. All diagnostic criteria must be fulfilled for a diagnosis of PoTS. A more in-depth look at each of the diagnostic criteria is discussed below:

Orthostatic Tachycardia Must Occur Within 10 minutes

The orthostatic HR increase of 30 bpm or more (or 40 bpm or more in youth 12–19 years of age) should occur within 10 minutes of standing [2]. In a study investigating tilt table testing and PoTS, 15 PoTS patients and 15 healthy controls underwent 30 minutes tilt table and active stand tests [5]. Orthostatic HR changes were evaluated at the 10 and 30 minutes tilt and stand time points. During head up tilt, if the 30 minutes time point and 30 bpm increase were used for diagnosis, 80% of the healthy controls would have met the HR criterion for PoTS diagnosis [5]. This is compared to only 60% within 10 minutes [5]. The increased orthostatic tachycardia in healthy controls during the longer tilt tests corresponds to physiological changes in the body that occur over a long period of orthostasis [5]. Blood return to the heart is decreased, as plasma is filtered through the microvasculature into the interstitial spaces, reducing blood volume [5, 6]. However, with the active stand testing, the excessive tachycardia in healthy controls was less pronounced, with only 47% of control participants meeting the PoTS HR criterion at the 30 minutes time point [5]. In the PoTS group, 14 of the 15 participants met the PoTS HR criterion during the 10 minutes tilt [5]. While the majority of PoTS patients met the HR criterion within the first 10 minutes, the majority of healthy control participants met the HR criterion by the 30 min time point. The 10 min duration for the head-up tilt serves to capture patients with PoTS, while limiting inadvertent diagnosis of healthy individuals (false positives).

Symptoms of Orthostatic Intolerance and Symptoms Independent of Orthostasis

Symptoms of orthostatic intolerance must be present in addition to orthostatic tachycardia (Table 2). If a patient has orthostatic tachycardia, but no (or minimal) orthostatic symptoms, they do not meet the requirements for a PoTS diagnosis. There must be clinical history of postural symptoms, but they are not required to be present at the time of orthostatic assessment. Clinical history may also reveal symptoms independent of orthostasis including gastrointestinal disturbances, fatigue, sleep problems [3] and difficulty concentrating [2].

Table 2

PoTS symptoms

Patients may also have symptoms related to comorbid disorders including, but not limited to, Ehlers-Danlos Syndrome, mast cell activation syndrome, and autoimmune disorders [7]. About 20–30% of patients may also experience syncope [8]. The mechanistic relationships between these disorders are not fully understood at this time.

PoTS is a Chronic Disorder

For a formal diagnosis of PoTS, the orthostatic intolerance should be chronic, and present for a period of 6 months or longer [4]. Some centers use a minimum of 3 months. Realistically, it is unusual for PoTS symptoms to disappear between 3 and 6 months, so these likely represent the same populations. Many people will develop orthostatic intolerance with acute infectious illnesses that can mimic PoTS. Unlike in PoTS patients, when seen with the flu, these symptoms will usually resolve after a few days [8]. Generally, if signs and symptoms of orthostatic intolerance are present for a prolonged period of time, clinical investigation and treatment should not be withheld, even if the time frame of symptom onset is less than 6 months.

Other Causes of Tachycardia

A detailed clinical history should rule out other disorders or physiological conditions that may have a similar clinical presentation to PoTS [3]. If a patient has another overt cause for their sinus tachycardia, a diagnosis of PoTS should NOT be made. A summary of these causes is provided in Table 3.

Table 3

Other causes of tachycardia to consider when diagnosing PoTS

Dehydration and Acute Blood Volume Loss

Dehydration leads to reduced circulating plasma volume, and compensatory tachycardia will result from the body’s attempts to compensate for the reduced fluid volume [4]. For example, patients with acute gastrointestinal bleeding may present with orthostatic tachycardia (≥30 bpm increase), indicating a plasma volume loss of 50% or more [9].

Deconditioning

Severe deconditioning and prolonged bed rest can lead to orthostatic intolerance and PoTS-like symptoms. A deconditioned patient may present with physiological findings including hypovolemia [10], cardiac atrophy [10] and/or reduced stroke volume [11]. It is important to determine if a patient is deconditioned secondary to PoTS, or if it is the primary pathogenic mechanism of their orthostatic intolerance [11]. This will help to guide treatment, from basic reconditioning in a deconditioned patient, to treatment of a patient with pathogenic mechanisms. Deconditioning is common in patients with PoTS. In a study of patients with PoTS or orthostatic intolerance but not PoTS, 93% of participants were found to be deconditioned [11]. However, whether deconditioning is cause or consequence is still under investigation. Some patients seen in clinic report periods of bedrest for 16 or more hours per day. While they are supine, their symptoms are improved, but the situation is self-perpetuating and deconditioning worsens. In cases of extreme bedrest and deconditioning, a PoTS diagnosis should not be made. Prolonged bedrest produces orthostatic intolerance similar to PoTS [12]. The physiological findings in individuals who have undergone prolonged bedrest are similar to the physiological findings in PoTS [12]. Similarly, research into spaceflight and microgravity has shown the presence of orthostatic intolerance in astronauts who have returned to earth. Prolonged exposure to low-zero gravity conditions alters the body’s physiological responses to standing. Cardiovascular autonomic regulatory mechanisms are disrupted, leading to a presentation of orthostatic intolerance comparable to individuals with PoTS [13].

A study of orthostatic intolerance and space flight involved astronauts engaging in a cardiovascular conditioning program for the duration of their space travel [14]. Astronauts who participated in this study were found to have reduced left ventricular mass as well as reduced plasma and red cell volume [14]. However, despite these physiological changes, the astronauts did not have significant orthostatic tachycardia suitable for PoTS diagnosis [14]. The authors suggest that the conditioning program while in space, helped to counter the effects of deconditioning experienced upon return to earth [14]. A separate study of 12 astronauts (n = 4 female) studied orthostatic hypotension and showed a similar result [15]. Throughout the 6 months the astronauts were in space, they participated in a resistance and endurance conditioning program. Upon return to earth, they were infused with 500–1000 mL of IV saline. No astronauts developed orthostatic hypotension upon return to earth, demonstrating that a regular conditioning program and acute volume loading were sufficient to prevent orthostatic intolerance [15].

Medications

Medications including vasodilators, diuretics, stimulants, as well as some antidepressant, antipsychotic, and anxiolytic medications may cause tachycardia [7, 16]. Medications that inhibit norepinephrine reuptake (via the norepinephrine transporter [NET]), can cause tachycardia due to increased stimulation of norepinephrine receptors. NET-inhibitor medications including atomoxetine and reboxetine [4], and serotonin-norepinephrine reuptake inhibitor (SNRI) agents including duloxetine and venlafaxine [8] are examples of these medications. Attention deficit hyperactivity disorder (ADHD) medication including methylphenidate has sympathomimetic effects, and stimulates adrenergic receptors, leading to tachycardia [12]. Drospirenone, a spironolactone-analog containing oral contraceptive may also promote a sinus tachycardia due to diuretic effects [16]. Caffeine and alcohol can also contribute to orthostatic tachycardia [7]. A summary of these medications and their effects are listed in Table 4.

Table 4

Medications that can cause PoTS-like tachycardia

Other Medical Conditions

Some medical conditions cause tachycardia that can be confused with PoTS. Anemia [16] can lead to tachycardia, as the body works to maintain adequate tissue oxygenation [17]. Clinical evaluation of the anemic patient may reveal pale skin, a history of heavy menstrual periods, and/or a vegetarian diet [12]. Hyperthyroidism [7, 16] can also cause tachycardia. Increased thyroid hormone (T3) alters the renin–angiotensin–aldosterone axis, with an end result of increased HR, and excessively increased cardiac output (50–300% larger) [18]. Patients may present with warm and moist skin, tremor, pretibial myxedema [12], weight loss and/or thyroid bruit [19]. A neuroendocrine tumour called pheochromocytoma [7, 12] presents with tachycardia independent of orthostasis [12]. Plasma metanephrine levels are often, and non-positionally, elevated in the presence of this condition [12]. Other medical conditions including pulmonary embolism, acute coronary syndrome, and arrhythmic disorders [12] should also be ruled out before making a diagnosis of PoTS. Acute infectious illness will also often present with transient symptoms of orthostatic intolerance, which should resolve within a few days [8].

Diurnal Variability in Orthostatic Tachycardia

PoTS patients experience variability of symptoms, and most often symptoms are worse in the morning [12]. Consideration of the time of testing should be given when diagnosing PoTS, as orthostatic tachycardia and symptoms may be lessened later in the day. A study of 54 PoTS patients found a significantly greater proportion of patients meeting PoTS diagnostic criteria in the morning than with testing in the evening (60 vs. 42%, p = 0.008) [20]. Another important finding in this study is the percentage of healthy controls who met the PoTS HR criterion in the morning but not in the afternoon (31 vs. 4%). Again, the presence of chronic orthostatic symptoms are important in the diagnosis of this clinical syndrome.

Similarly, women may experience fluctuations in symptom severity during different phases of the menstrual cycle. Estradiol and progesterone regulate fluids and sodium in the body [21]. A study of women with PoTS investigated the function of the renin–angiotensin–aldosterone system at different phases of the menstrual cycle [22]. Prolonged standing tests (up to 2 hours), were conducted to compare participants responses during the early follicular phase (EFP; low estrogen and progesterone) and mid-luteal phase (MLP; high estrogen and progesterone) phases of the menstrual cycle [22]. Plasma renin activity and aldosterone levels with a 2 hours standing test were higher during MLP than during EFP in PoTS patients [22]. The authors conclude that the increased estrogen and progesterone in the MLP are associated with increased renal hormones and exaggerated volume retention, leading to improved standing tolerance [22]. In a separate study, participants reported an increase in lightheadedness in the late-luteal and menstrual phases of their cycle [23]. These research findings demonstrate that menstrual cycle phase should be a consideration in the evaluation of PoTS.

Common Misconceptions Regarding the Diagnosis of PoTS

Tilt Table Testing

PoTS can be diagnosed with either a tilt table test or active stand testing [5]. Orthostatic tachycardia is likely to be more pronounced with tilt due to the passive standing mechanisms and lack of engagement of the skeletal muscle pump [5]. However, a tilt table test is not required for PoTS diagnosis [12]. A simple free stand for 10 minutes with repeated measurements of HR and blood pressure is a valid diagnostic test [5]. Further information comparing active stand and tilt testing in the diagnosis of PoTS is included in chapter Autonomic Testing:​ Active Stand and Tilt Table Test of this book.

Specialist Referral

A PoTS diagnosis can be made by a general clinician using an in office active stand test in combination with clinical assessment and ECG [3].

Syncope

A common misconception is that patients must faint in order to meet the criteria for PoTS. In reality, only about 20–30% of patients with PoTS will experience syncope [8]. A patient with PoTS could also have a syncope diagnosis, but syncope is not a requirement for a PoTS diagnosis. Prolonged pre-syncope is extremely common, and patients frequently report they are going to faint, but most often frank syncope does not occur. PoTS is primarily a disorder of feeling faint rather than a fainting disorder.

Distinguishing PoTS from Other Types of Orthostatic Intolerance

There are several different causes of orthostatic tachycardia, and it is important to rule out these other types of orthostatic intolerance to ensure an accurate diagnosis of PoTS.

Orthostatic Tachycardia Without Orthostatic Symptoms

Some patients may present with excessive orthostatic tachycardia in the absence of orthostatic symptoms. The recent increase in consumer HR monitoring devices may be contributing to this increased presentation in clinic as patients are able to readily monitor their own data. However, without orthostatic symptoms, PoTS should not be diagnosed. The mechanistic differences behind orthostatic tachycardia with and without symptoms are not well understood.

An increase in HR with exercise is not PoTS (even if perceived to be excessive), and should not be diagnosed as such. PoTS is a clinical syndrome and requires the presence of symptoms [8].

Orthostatic Symptoms Without Orthostatic Tachycardia

Some patients may present with symptoms of orthostatic intolerance without meeting the corresponding HR criterion. Both criteria are required for PoTS diagnosis. These patients may be diagnosed with orthostatic intolerance, but not PoTS. It is important to note that orthostatic intolerance without orthostatic tachycardia is a legitimate diagnosis and warrants appropriate treatment. Some patients may seek out an incorrect PoTS diagnosis in order to validate their illness. A representative diagram is shown in Fig. 1.

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Fig. 1

For a diagnosis of PoTS, both orthostatic tachycardia and orthostatic symptoms are required

Inappropriate Sinus Tachycardia (IST)

IST is a disorder where excessive sinus tachycardia is present independent of position. HR is sustained >100 bpm at rest in association with symptoms of palpitation [3]. IST presents in the absence of a clear causative medical condition, physiological process, or medication effect [24]. Similar to PoTS, IST primarily presents in adolescent and young adult females [24]. Mechanistic similarities between IST and PoTS have been proposed, however, PoTS is distinct in that the development of tachycardia only occurs with orthostasis [24]. If patients continue to have tachycardia independent of orthostasis, a PoTS diagnosis would not be appropriate.

Orthostatic Hypotension (OH) and Initial Orthostatic Hypotension (IOH)

OH is defined as a decrease in BP >20/10 mmHg within 3 minutes of standing [25]. PoTS patients may experience OH at times, especially if they are hypovolemic, but they must also experience an orthostatic HR increase independent of a decrease in BP (at other times) to meet PoTS diagnostic criteria [8].

IOH is defined as a transient decrease in BP >40 mmHg systolic BP or >20 mmHg diastolic BP within 15 seconds of standing [2]. IOH quickly resolves within 20–30 seconds of standing [26]. IOH occurs in seemingly young, healthy individuals and the pathophysiology has not been fully elucidated [26]. Proposed mechanisms include the role of the muscle pump, as well as sympathetic withdrawal and/or vasodilation upon standing [26]. Reflex tachycardia in response to these decreased pressure states can result as the baroreceptors detect fluid shifts due to gravity. In IOH, this tachycardia should resolve as the BP returns to normal. Although PoTS patients may also experience IOH, PoTS should not be diagnosed in such cases where tachycardia is only observed in response to the acutely decreased BP, and is not sustained when the BP returns to a normal level (Fig. 2).

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Fig. 2

Blood pressure and heart rate trends in a normal individual and in disorders orthostatic intolerance. 1. Normal blood pressure and heart rate response upright posture. A gradual heart rate increase is observed over time. Blood pressure remains unchanged. 2. Postural Tachycardia Syndrome (PoTS): Upon assumption of upright posture, excessive orthostatic tachycardia is observed. Blood pressure remains relatively unchanged. 3. Initial Orthostatic Hypotension (IOH): Upon upright posture, blood pressure transiently decreases and then recovers. A brief reflex tachycardia is observed. 4. Orthostatic Hypotension (OH): Upon upright posture, blood pressure continually declines. A reflex tachycardia is observed. Figure modified from [31]

Supine Bradycardia: Patients with a low resting HR may have an orthostatic HR increase that meets or exceeds PoTS criteria. However, a PoTS diagnosis may not be appropriate unless their upright HR is significantly elevated [2].

Diagnosing PoTS in the Pediatric Patient

Children and youth are more prone to physiological orthostatic tachycardia than adults [27]. With aging into later adulthood, physiological orthostatic tachycardia decreases even further. Therefore, many youths may experience orthostatic tachycardia >30 bpm when upright, but are asymptomatic. A study established normal orthostatic HR increase in 100 healthy youth age 12–19 using active stand testing [28]. The mean HR upon upright posture was 21.5 ± 21.2 bpm (2 standard deviations above the mean) [28]. The established Schondorf and Low criteria indicate PoTS should be diagnosed when the HR is 2 standard deviations above the mean or more [1]. Based on this study, the HR target would be >42.7 bpm [28] for a diagnosis of PoTS. A separate study of 108 healthy youth found 42% increased their HR by 30 bpm or more when upright during tilt table testing [27]. To adjust for this common tachycardia in children and youth, an orthostatic HR increase of >40 bpm must be achieved for a diagnosis of PoTS in patients 12–19 years of age. A period of ≥3 months may be suitable to establish chronicity of symptoms in a pediatric population [29]. The standard test to diagnose PoTS in a pediatric population is a 10 min head-up tilt test [3, 29]. Although active stand testing is a validated diagnostic test in adults [5], it has not been validated for a pediatric population [29]. However, a research study has used standing as a diagnostic test for PoTS in 93 youth (mean age 17) while investigating appropriate duration of testing [30]. Participants stood freely with their back against a wall for 10 minutes while orthostatic vitals and symptoms were measured [30]. Notably this work found that if upright tests were conducted for only 2 or 5 minutes, 54 and 27% of participants with PoTS, respectively, would be misdiagnosed [30]. The researchers also used a 2 minutes supine post-stand measurement, to determine the value of lowest supine HR, as pre-stand supine HR was often higher than post-stand supine HR [30]. With this change, an additional 14% of adolescents met the PoTS criteria. Measurement of the lower, post-stand HR may be a more accurate value for diagnosis of PoTS [30]. Although, as mentioned, the stand test has not been validated in a pediatric population, it can be used for diagnosis. This is especially true when access to a testing center or specialist care may be limited and may be barrier to diagnosis and appropriate treatment.

Conclusions

The primary diagnostic criteria for PoTS require an excessive orthostatic tachycardia within 10 min of assuming upright posture in association with chronic symptoms of orthostatic intolerance. This must occur chronically and in the absence orthostatic hypotension, and other disorders or medications which could independently cause orthostatic tachycardia. A thorough clinical review and consideration of related disorders is critical to ensure the accurate diagnosis of PoTS and appropriate clinical treatment plan.

Acknowledgments

The authors would like to acknowledge the many patients that have volunteered their time to contribute to this body of work. Their participation is critical to the ongoing investigation of PoTS.

Funding

Dr. Raj has a research grant related to Postural Tachycardia Syndrome from the Canadian Institutes of Health Research, Ottawa, Canada (grant number MOP142426). Dr. Lloyd has a post-doctoral scholarship through the Cumming School of Medicine. Kate Bourne holds a Canadian Institutes of Health Research Canada Graduate Scholarship.

Disclosures

Dr. Raj is a network investigator of the Cardiac Arrhythmia Network of Canada (CANet; London, Ontario, Canada). Dr. Raj serves on the Medical Advisory Board of Dysautonomia International and PoTS UK, both without financial compensation. Dr. Lloyd has reported that he has no relationships relevant to the contents of this chapter to disclose. Kate Bourne has also reported that she has no relationships relevant to the contents of this chapter to disclose.

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