Postural orthostatic tachycardia syndrome

What is PoTS?

Postural orthostatic tachycardia syndrome (PoTS) is a group of disorders where symptoms arise from abnormal autonomic response to the upright position. On becoming upright, people with PoTS develop tachycardia and symptoms of orthostatic intolerance. It is frequently missed or misdiagnosed, and may be primary or secondary in origin¹ .

Who gets PoTs syndrome? (Epidemiology)²

PoTS is the most common form of orthostatic intolerance in young people, typically affecting young women³ .

The prevalence of PoTS syndrome in the UK is estimated to be 2 in 1,000. It is a diagnosis which is thought to be missed frequently. It is five times as common in women as it is in men. It can occur at any age but is most common between the ages of 15 and 50.

What causes PoTs? (Aetiology)^{4 5 6}

The normal response to standing up is peripheral vasoconstriction and an increase in heart rate of up to 20 beats per minute.

In PoTS, there is an abnormal response by the autonomic nervous system to upright posture. In some, mechanism is lack of vasoconstriction on standing causing pooling of blood in the abdomen and limbs, reduced venous return to heart, compensatory tachycardia and altered cerebral circulation² .

The cause of PoTS syndrome is unknown but is likely to be heterogeneous.

Primary PoTS

PoTS syndrome often starts abruptly and has been known to occur following pregnancy, surgery, immunisation, viral infection, sepsis and trauma. An autoimmune element has been proposed in these cases. There is also a developmental form of PoTS, affecting teenagers around the age of 14. PoTS symptoms begin gradually and most resolve fully in time. A genetic defect has been identified in certain cases, known as hyperadrenergic PoTS. People with this type of PoTS syndrome have symptoms associated with high adrenaline (epinephrine) levels in addition to orthostatic intolerance, and the condition tends to run in families.

Secondary PoTS

• Association with autonomic neuropathy - for example, in people with:

  • Diabetes mellitus.

  • Amyloidosis.

• Post-viral - eg, long COVID, glandular fever.

• Hypermobility syndromes.

• Sjögren's syndrome.

• Alcoholism.

• Systemic lupus erythematosus (SLE).

• Chemotherapy.

• Deconditioning after prolonged bed rest.

• Heavy metal poisoning.

• Sarcoidosis.

• Cancers.

• Strong association with ME/chronic fatigue syndrome.
  

PoTS symptoms⁵

The hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a more than six-month history of symptoms that are relieved by recumbence⁷ .

History

There is great variety in PoTS symptoms which may be experienced and in the degree of severity. They are usually prompted or exacerbated by standing or sitting, or long periods of standing or sitting. Symptoms may also be exacerbated by exertion, heat, alcohol or eating. Possible PoTS symptoms include:

• Dizziness or light-headedness.

• Palpitations.

• Fatigue.

• Anxiety.

• Syncope or pre-syncope.

• Weakness, poor exercise tolerance.

• Nausea.

• Tremulousness.

• Sleep disturbance.

• Headache.

• Shortness of breath.

• Chest pain.

• Bloating.

• Diarrhoea.

• Sweating.

• Anxiety.

• Blurred vision.

• Poor concentration or memory.

• Neck and shoulder pain.

The most common PoTS symptoms are light-headedness, palpitations, pre-syncope and weakness.

Examination

• Pulse: the diagnostic feature is a sustained increase in pulse rate on standing.

• Blood pressure: usually normal or increased.

• Peripheral circulation: there is often a dark red-blue discolouration of the lower extremities on standing and the feet are cold. This is called dependent acrocyanosis.

• Stand test or tilt table test: for the stand test, which can be done in primary care, pulse and BP are measured supine, then after standing for 2, 5 and 10 minutes. For the table tilt test, after resting, the person is tilted up by 60° for 45 minutes.

Diagnostic criteria⁶

The gold standard for PoTS diagnosis is head-up tilt test with non-invasive beat-to-beat haemodynamic monitoring⁸ .

• Sustained rise in heart rate of ≥30 beats per minute within 10 minutes of standing or on tilt test in the absence of orthostatic hypotension. (Increment of 40 beats per minute for those aged 12-19. Criteria may not be applicable for those with a low resting heart rate).

• Standing heart rate is often >120 beats per minute.

• As well as orthostatic tachycardia, there may be symptoms of cerebral hypoperfusion and autonomic overactivity which are relieved by lying down.

Investigations

Investigations are aimed at excluding the differential diagnoses (see below) and secondary causes. They may therefore include:

• Blood tests:

  • FBC.

  • U&Es.

  • Calcium.

  • TFTs.

  • Cortisol.

  • Autoantibodies.

  • Catecholamines (checked in supine and upright positions).

• ECG.

• 24-hour ECG and 24-hour BP monitoring.

• Electroencephalogram (EEG).

• Head up tilt (HUT) test as described above.

Differential diagnosis^{4 6}

• Inappropriate tachycardia syndrome (the heart rate increases in a way which is out of proportion to physical needs but not affected by posture).

• Chronic fatigue syndrome.

• Anxiety.

• Orthostatic hypotension (similar symptoms but BP lower on standing).

• Phaeochromocytoma (similar symptoms but distinguish from PoTS by measurement of plasma or urinary catecholamines).

• Thyrotoxicosis.

• Cardiac arrhythmias.

• Side-effects of medication such as vasodilators, beta agonists and diuretics.

PoTS treatment and management^{2 4 5 9}

Because PoTS has a variety of causes, no single treatment is effective for everyone, and combinations of approaches are often needed. Non-pharmacological therapy includes educating patients to avoid orthostatic intolerance triggers and increasing their understanding of the mechanisms of PoTS. Increasing blood volume by adding extra salt to the diet and drinking more fluids, as well as reducing venous pooling by using compression garments, are recommended. Medications that are commonly used include beta-blockers, midodrine, fludrocortisones, central sympatholytic agents, pyridostigmine, ivabradine, octreotide, and erythropoietin¹⁰ .

Review of medication

Where possible, stop any medication which may be causing or contributing to PoTS symptoms. This includes :

• Alpha-blockers.

• Beta-blockers.

• Calcium-channel blockers

• Angiotensin-converting enzyme (ACE) inhibitors.

• Diuretics.

• Nitrates.

• Phenothiazines.

• Tricyclic antidepressants.

• Monoamine-oxidase inhibitors.

• Opiates.

• Phosphodiesterase-5 inhibitors.

Referral

Refer ideally to a physician with a special interest in PoTS syndrome. This will usually be a specialist cardiologist, a syncope clinic or an autonomic neurovascular clinic.

Non-pharmacological management

• Increase fluid intake (2-2.5 litres per day).

• Increase salt intake (3-5 g per day). (Not for the hyperadrenergic form.)

• Raise the head of bed.

• Exercises for the lower legs to improve muscle strength and pump action. Exercise programmes must be graduated.

• Compression stockings.

• Changing eating patterns - for example, eating smaller meals more frequently.

• Avoidance of alcohol and other trigger factors (such as heat or sitting still for long periods of time).

• Psychological support or cognitive behavioural therapy (CBT) may be required.

Pharmacological management

No medication is licensed for PoTS syndrome and pharmacological therapy should always be initiated by a specialist.

Options which have been used for PoTS syndrome include:

• Fludrocortisone (causes salt and water retention and sensitises alpha-adrenergic receptors).

• Selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) (stimulates the standing vasoconstriction reflex).

• Pyridostigmine (improves neural transmission).

• Erythropoietin (causes volume expansion and vasoconstriction. Use is dependent on haematocrit levels).

• Sodium chloride infusions.

• Vasoconstrictors such as octreotide, midodrine, ergotamine and methylphenidate.

• Clonidine (reduces sympathetic nervous system tone - hyperadrenergic form only).

• Ivabradine (sinus node blocker).

• Methyldopa (false neurotransmitter).

• Beta-blockers are occasionally helpful, although often make symptoms worse. Labetalol may be an option because it is a combined beta/alpha 1 blocker.
  

PoTS prognosis^{4 5}

Although long-term prognosis of PoTS is poorly explored, around 50% of patients spontaneously recover within 1-3 years⁸ .

Prognosis depends on the type and the underlying cause. It is better in younger people. 80% of developmental PoTS symptoms resolve within a few years. Those cases which follow viral infections tend to resolve spontaneously within a few years. 90% respond to some form of treatment. PoTS syndrome may cause significant reduction in quality of life and may lead to anxiety and depression.

Severe orthostatic intolerance may lead to people being bed-bound or wheelchair-dependent. Life expectancy is not thought to be affected² .