CASE
A university student, aged 20 years, presented to her general practitioner (GP) with a one-year history of fatigue, palpitations, tachycardia and postural dizziness. This was on a background of insomnia, hyper-mobility, tension headaches and chronic constipation. The patient had developed worsening fatigue, now triggered with minimal exertion, as well as worsening heat intolerance, difficulty concentrating and daily recurrent orthostatic dizziness. These persistent symptoms markedly limited her mobility and functional capacity to complete activities of daily living.
Prior examination findings included a resting heart rate (HR) fluctuating between 160–180 beats per minute (bpm) and a standing HR of 200–220 bpm without orthostatic hypotension. Her baseline bloods and electrocardiogram (ECG) were unremarkable. The patient was subsequently referred and diagnosed with postural orthostatic tachycardia syndrome via a tilt table test (TTT).
Question 1
What is postural orthostatic tachycardia syndrome (POTS)?
Question 2
What is the pathophysiology of POTS?
Question 3
What are the diagnostic criteria for POTS?
Question 4
What is involved in the initial work-up of a patient suspected to have POTS?
Answer 1
POTS is a multi-system disorder characterised by symptoms of orthostatic intolerance, particularly a rise in HR when standing, without marked orthostatic hypotension or concomitant cause for tachycardia.1,2 Patients often experience palpitations, weakness or lightheadedness, which improve upon being seated.1 Common co-existing conditions include, but are not limited to, hyper-mobility spectrum disorder, fibromyalgia and migraines.1,3 Symptom onset can be precipitated by a stressful event, commonly viral infections.2 Up to 80% of POTS patients are female, often from a White background. The most common age of symptom onset is 14 years (mean age 21±12 years).3
Answer 2
Three main pathophysiologies that underlie POTS are: (1) autonomic neuropathy; (2) hypovolemia; and (3) a hyperadrenergic state.4 Often, the aetiology is mixed and complicated by comorbid autoimmune conditions or genetic mutations.5 Addressing these pathophysiologies underlies the management of POTS.4
Autonomic neuropathy of small postganglionic sudomotor fibres, mainly in the feet, have been reported in up to 50% of POTS patients. Consequent impairment of sympathetic tone causes reduced venoconstriction and venous pooling in the abdomen, pelvis and lower extremities.6 Hypovolemic POTS is characterised by low plasma blood volume and a 24-hour urine sodium concentration <100 mmol/L, caused by a dysfunctional renin-angiotensin-aldosterone system. Hyperadrenergic POTS is characterised by a rise in systolic blood pressure (BP) of >10 mmHg during a 10-minute TTT and a plasma noradrenaline level >600 pg/mL.4,7 A subset of patients also have autoantibodies to adrenergic receptors, or deficiency in noradrenaline transporters.4
Answer 3
As per the 2015 consensus statement by the Heart Rhythm Society,7 the following four features must be met to diagnose POTS:
- sustained HR increase of ≥30 bpm (or ≥40 bpm if the patient is aged 12–19 years) within 10 minutes of upright posture
- absence of orthostatic BP drop ≥20/10 mmHg
- symptoms of orthostatic intolerance that are worse while upright, with rapid improvement upon return to a supine position for >6 months
- absence of other conditions that could explain sinus tachycardia.
Answer 4
Initial investigation of suspected POTS should include orthostatic vital sign measurements to confirm postural tachycardia, and a 12-lead electrocardiogram and a 24-hour Holter monitor to exclude an arrhythmia. Pathology tests should screen for other causes of tachycardia/presenting symptoms, including a full blood count, iron studies, active vitamin B12, electrolytes, renal function, thyroid function tests, plasma noradrenaline and morning cortisol. A patient might also be referred for a TTT to confirm postural variability in HR between supine and standing without significant postural changes in BP.1,5
Case continued
The patient was commenced on Fludrocortisone and Propranolol. She was advised to increase her daily fluid and salt intake, wear compression stockings and see a physiotherapist and dietitian to aid in reconditioning.
Question 5
What are the principles of management of POTS?
Answer 5
Management for patients with autonomic neuropathy aims to promote venous return via compression garments or increasing peripheral vasoconstriction, commonly with midodrine. Management of hyperadrenergic POTS is two-fold: (1) sympathetic suppression (commonly with beta blockers); or (2) parasympathetic stimulation (often with pyridostigmine). Management of hypovolemic POTS focuses on volume expansion. Increasing daily sodium and fluid intake, as well as Fludrocortisone or Desmopressin, can be considered.5,6 Suggestions for non-pharmacological and pharmacological management are given in Tables 1 and 2.
| Table 1. Non-pharmacological options for management of POTS5 |
| Strategy |
Effectiveness |
| Exercise training and gradual reconditioning |
Class IIa recommendationA |
| Sodium intake >10 g/day and fluid intake of at least 2.5 litres/day |
Class IIb recommendationA |
| Class 2 compression garments >30 mmHg of pressure |
Class Ib recommendationA for venous insufficiency; shown to have symptomatic improvement in POTS |
POTS, postural orthostatic tachycardia syndrome.
AIb, strong recommendation where benefits clearly outweigh risks, based on moderate-quality evidence; IIa, weak recommendation where benefits are closely balanced with risks, based on high-quality evidence; IIb, weak recommendation where benefits are closely balanced with risks, based on moderate-quality evidence. |
| Table 2. Pharmacological options for management of POTS5,6 |
| Goal |
Examples of medications |
Mechanism of action |
Effectiveness |
Possible adverse effects |
| Reducing upright sinus tachycardia/sympathetic tone |
BBs (eg propranolol, 10–40 mg tid; bisoprolol, 2.5–5 mg bid; metoprolol, 25–100 mg daily; atenolol, 12.5–50 mg daily) |
β-AR antagonist8 |
- Class IIb recommendation10
- Especially useful for hyperadrenergic phenotype
|
- Bradycardia, hypotension, fatigue, syncope
- Caution recommended for patients with asthma
|
| Ivabradine (2.5–5 mg bd) |
Inhibits selective cardiac pacemaker current (If) slowing sinoatrial node firing9 |
- Not currently part of first- or second-line guidelines, shown to improve symptoms with very few side effects
- Effective when BBs not well tolerated
|
- Bradycardia, hypertension, atrial fibrillation, visual brightness
|
| Enhancing vasoconstriction/venoconstriction |
Midodrine (2.5–10 mg bd) |
Direct α1-AR agonist |
- Class IIb recommendation,10 might be especially useful for hypovolemic subtype or patients with pronounced orthostatic intolerance
|
- Supine hypertension, paresthesias, urinary retention
|
| Clonidine (0.2–0.6 mg bd) |
Direct centrally acting 2-AR agonist |
- Class IIb recommendation,10 recommended for hyperadrenergic phenotype or for patients with hypertension on standing
|
- Headache, generalised rash, fatigue and sedation
|
Pyridostigmine
(30–60 mg bd/tds) |
Acetylcholinesterase inhibitor |
- Class IIb recommendation,10 can be considered in possible neuropathic phenotype
|
- Abdominal pain, diarrhoea, vomiting
|
| Augmenting blood volume |
Fludrocortisone (0.1–0.2 mg
one daily) |
Increases sodium reabsorption and enhances sensitivity of α-AR |
- Class IIb recommendation, might be especially useful for hypovolemic subtype
|
- Hypertension, hypokalaemia
|
| Desmopressin (0.1–0.4 mg bd) |
Vasopressin analogue |
- Limited evidence but symptomatic improvement in tachycardia reported6
|
|
| α-AR, alpha adrenoreceptor; β-AR, beta adrenoreceptor; BBs, beta blockers; IIb, weak recommendation where benefits are closely balanced with risks, based on moderate-quality evidence; POTS, postural orthostatic tachycardia syndrome. |
Key points
- POTS is a multi-system syndrome characterised by symptoms of orthostatic intolerance, usually seen in young women.
- Diagnosis is on a combination of orthostatic intolerance for >6 months and increase in HR ≥30 bpm within 10 minutes of upright posture in the absence of orthostatic hypotension or other explanatory diseases.
- Management is both non-pharmacological and pharmacological, and is aimed at expanding blood volume, enhancing venous return and reducing tachycardia.