Postural orthostatic tachycardia syndrome

Need to know:

• Postural orthostatic tachycardia syndrome (POTS) presents with orthostatic intolerance, frequently associated with multi-system symptoms.
• In the primary care setting, diagnosis can be undertaken via active standing test. A positive test is met with a sustained heart rate rise of 30 beats per minute or greater (or 40 beats per minute or greater in 12-19-year-olds) with the absence of orthostatic hypotension.
• First-line therapy is lifestyle modification, including fluid loading, high salt diet, use of compression wear and a graded exercise program. 
• Pharmacotherapy has a limited evidence base but is utilised to improve day-to-day function and reduce symptom burden in those with persistent symptoms despite lifestyle modification.
  

Postural orthostatic tachycardia syndrome is a clinical syndrome characterised by orthostatic tachycardia and intolerance. The condition has gained significant interest in recent times, as it has remarkably similar symptomatology to that observed in post-acute sequalae of SARS-CoV-2 infection (long COVID) and can manifest post-virally.¹ 

Individuals presenting with postural orthostatic tachycardia syndrome (POTS) often report diverse symptoms in addition to those related to postural change. As this is a chronic multi-system disorder, individuals with POTS are likely to benefit from early multidisciplinary intervention with involvement of allied health professionals and relevant specialists.

Clinical presentation

POTS is a complex chronic disorder that occurs as a result of underlying autonomic dysfunction. Those affected can present with a myriad of symptoms based on the degree of dysautonomia and organ systems affected. The condition is typically poorly recognised by healthcare professionals, with frequent misdiagnosis and/or significant diagnostic delay (median around 24 months).² POTS has a significant female preponderance (representing 85% of those affected) with onset often in the adolescent years. 

In some individuals, the onset follows a specific trigger, such as infection (mostly viral), trauma, concussion, or times of significant hormonal change (eg, onset of menses, post-partum, menopause). In others, the onset is more insidious, with a gradual increase in symptoms over time. 

Several comorbidities are commonly seen in patients with the condition, including joint hypermobility (hypermobile spectrum disorder or hypermobile Ehlers-Danlos syndrome), migraine, autoimmune conditions, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia.³ 

The key feature of POTS is orthostatic tachycardia with absence of postural blood pressure reduction.⁴ The presenting symptoms of orthostatic intolerance may include dizziness, light-headedness, brain fog, pre-syncope/syncope, palpitations, chest pain or discomfort, headache, nausea, visual disturbance, fatigue and tremulousness.⁵ These symptoms typically improve with recumbence. 

It is extremely common for individuals to report a constellation of non-orthostatic symptoms, including sleep or cognitive disturbances, bloating/constipation, thermo­regulatory disturbance, urinary symptoms and exercise intolerance. 

POTS is a fluctuating condition, often involving ‘flares’ interspersed with periods of relatively well-controlled symptoms. The aetiology is unclear, although several mechanisms have been proposed, including autoimmunity.³ Although POTS has been categorised into various sub-types (such as hypovolaemic, neuropathic or hyperadrenergic), there is significant crossover, and an individual may experience features of more than one subtype.⁶ 

Diagnosis

Diagnosis is based on symptomatology, in addition with tachycardia observed with standing. It is generally agreed that symptoms should be present for at least three months before POTS can be confirmed. 

Additionally, other potential causes or contributors to orthostatic tachycardia must be excluded. These include medications, such as sympathomimetics and anticholinergic agents, and medical conditions, such as anaemia, dehydration, fever, pain, anorexia nervosa, hyperventilation, severe deconditioning, hyperthyroidism and phaeochromocytoma. 

In the primary care setting, to determine change in heart rate and blood pressure, a 10-minute active standing test can be performed after the patient has been supine for five minutes. This involves assessing heart rate and blood pressure upon standing, over 10 minutes. A positive standing test is a sustained heart rate rise of 30 beats per minute or greater in adults, or 40 beats per minute or greater in those aged 12-19 years, in the absence of orthostatic hypotension (drop in systolic blood pressure of greater than 20mmHg), within three minutes of standing.⁵ An absolute heart rate of 120 beats per minute or greater at any time during the standing test is also diagnostic.⁷ 

It should be noted that the heart rate criteria have been disputed when clinical suspicion is high, particularly in adolescents.⁸ Diurnal variations in heart rate responses to orthostatic stress have been observed in this population and therefore testing is better performed in the morning. 

Given the fluctuating nature of the condition, a negative active standing test does not conclusively exclude a POTS diagnosis. For those with suggestive symptoms but who do not meet the heart rate criteria, the Canadian Consensus Statement suggests a diagnosis of postural symptoms without tachycardia (PSWT), acknowledging that that there must be a high index of clinical suspicion and that the criteria for POTS may be met at a future time point.⁹ 

Dependent acrocyanosis, whereby the feet or hands discolour or appear mottled with prolonged upright posture during active standing test, is commonly observed in this population. 

Baseline blood tests such as full blood count, serum electrolytes, iron studies and thyroid function tests should be considered, and prompt investigation into abnormalities that may contribute to symptomatology or warrant investigation for other conditions. A tilt table test can be considered if it is deemed unsafe to perform the active standing test or if the patient is unable to stand. 

Management

Non-pharmacological
In the absence of curative treatment, management of POTS is largely directed at alleviating symptoms, although most interventions have a rather limited evidence base.¹⁰ Initial strategies involve lifestyle modifications to improve and support blood volume. These include fluid loading, high salt diet, use of compression wear and graded recumbent exercise (see figure 1).

Fluid loading can be achieved by recommending consumption of 2-3 litres per day. The majority of this should come from water, although electrolyte drinks are frequently utilised in this population. In the absence of any contradictions, a high salt diet (up to 10g per day) is recommended, achieved by increasing intake of high salt foods and adding salt to meals.⁹  Additional salt tablets (600mg) can be used (two tablets, three times per day), although these may worsen gastrointestinal symptoms and/or be poorly tolerated. 

Compression garments may assist in supporting blood flow with upright posture, with one study demonstrating improved stroke volume on head up tilt table testing with both full (abdominal and full leg) and abdominal-only compression.¹¹ 

Exercise is helpful but often requires commencement of recumbent activity before more upright activity can be tolerated.¹² In a small ‘before and after’ study, six months of unsupervised home exercise training enhanced quality of life, reduced supine and standing heart rates, and reduced the frequency of syncope.¹³ Guidance from an exercise physiologist who is familiar with POTS is often helpful to avoid post-exertional malaise, where symptoms acutely exacerbate within 24 hours of exercise. 

Common triggers to avoid include hot, humid environments, hot showers, scenarios that require prolonged standing, and excessive alcohol, tea, coffee or energy drink intake. Online support groups and patient advocacy organisations can provide additional support to this population and their carers (see Online resources). 

For those whose symptoms are well controlled with lifestyle modifications, specialist review may not be required, as in the absence of curative treatments, therapy is largely directed at managing symptomatology and optimising function. 

Pharmacological
There are several pharmacological options to support ongoing symptoms that are refractory to lifestyle management alone. Medications used to ameliorate orthostatic tachycardia include ivabradine, a selective funny current (If) inhibitor (the funny current is a mixed sodium–potassium inward channel in the sinoatrial node) or beta blockers (propranolol or metoprolol). 

Some individuals with hyperadrenergic-type POTS may have high blood pressure along with tachycardia, that improves on recumbence and with heart rate slowing medications. Therefore, beta blockers should be used cautiously, even with apparent initial hypertension, as they carry a risk of hypotension following adequate rate control. 

Fluid and volume retention can be assisted with the addition of fludrocortisone. Midodrine is an effective alpha-adrenergic agonist that can also be helpful in supporting upright posture through vasoconstriction and is generally well tolerated. Unfortunately, neither ivabradine nor midodrine are listed on the Pharmaceutical Benefits Scheme for POTS and therefore pose a substantial cost to the users. Specialist POTS cardiologist or physician referral to assist with titration of these medications may be advantageous, especially if the primary care practitioner is unfamiliar with these treatment options. 

A small proportion of patients with POTS require intermittent or chronic intravenous fluid therapy alongside pharmacotherapy.

Multidisciplinary care
A significant proportion of patients with POTS have multi-system symptoms despite good heart rate and blood pressure control, as a result of their autonomic dysfunction. Many experience significant impacts on their ability to attend school or work and participate in social activities, often resulting in detrimental mental health effects and financial hardship. 

Multidisciplinary management is frequently warranted, potentially including neurology, orthopaedic, gastroenterology, pain physician, rheumatology, immunology, psychiatry and vascular surgery input. Additionally, allied healthcare is often required, including physiotherapy, exercise physiology, dietetics, occupational therapy and psychology involvement. 

Prognosis

The trajectory of POTS is largely unknown due to the lack of long-term data. However, in a cohort of adolescents diagnosed with POTS, most reported improvement, but only 19% reported symptom resolution over five years of follow-up.¹⁴ 

Conclusion

POTS is a heterogenous and fluctuating condition, with individuals often experiencing multi-system symptoms beyond those of orthostatic tachycardia and intolerance. Treatment is largely directed at managing symptoms and improving function. Specialist referral is often needed for those with more severe multi-system symptoms. In Australia, this is currently limited by the select number of specialist centres familiar with managing this condition, placing increased pressure on the primary care sector to diagnose and manage this complex illness. 

Tips from the authors

• In our clinical experience, there appears to be little yield in referring patients for tilt table testing – in most instances, an active standing test is satisfactory.
• While lifestyle modification does provide some benefit to reducing symptom burden, the vast majority of patients require some form of pharmacotherapy.
• Clinically we have found that initial heart rate and volume/vasopressor therapies may also improve many non-orthostatic symptoms.

Resources:

• The Australian POTS Foundation
  potsfoundation.org.au
• Dysautonomia International
  dysautonomiainternational.org
• Standing Up To POTS
  standinguptopots.org

Professor Dennis H Lau is a clinical professor and cardiac electrophysiologist at the University of Adelaide and Royal Adelaide Hospital, SA. 

Celine Gallagher is a clinical nurse consultant and postdoctoral fellow at the University of Adelaide, SA.

Marie-Claire Seeley is a clinical nurse consultant and PhD student at the University of Adelaide, SA.

Acknowledgements

Financial disclosures: Ms Seeley is supported by an Australian Government Research Training Program Scholarship. Mrs Seeley and Dr Lau are supported by research funding from Standing Up To POTS.

References on request from kate.kelso@adg.com.au