Postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by a sustained increase in heart rate during standing, without associated orthostatic hypotension. It predominantly affects adolescent girls and young to middle-aged women. Although the pathogenesis of POTS remains unclear, it is often precipitated by viral illness. Clinical features include orthostatic symptoms (e.g., lightheadedness, palpitations, blurred vision) and nonorthostatic symptoms (e.g., fatigue, cognitive impairment). The active stand test is used to confirm the diagnosis; a tilt table test may be obtained if the active stand test is inconclusive or not tolerated by the patient. Additional workup should be performed as needed to rule out differential diagnoses of POTS and evaluate for conditions associated with POTS. Management focuses on reducing symptoms and optimizing quality of life. Self-management strategies involve increased fluid and salt intake, compression garments, and personalized exercise therapy. Pharmacological therapy, which is often required in addition to lifestyle modifications, includes agents that increase venous return (e.g., midodrine, fludrocortisone) and heart rate-lowering drugs (e.g., propranolol).

• Prevalence
  • Precise nationwide prevalence data are limited.
  • Previous estimates indicate approx. 0.2–1% ^[1]
  • Likely significantly higher after the COVID-19 pandemic ^[2]
• Sex: ♀ > ♂ (4:1) ^[1]
• Age: typically affects individuals 12–50 years of age ^[1]

POTS predominantly affects adolescent girls and young to middle-aged women. ^[1]

Epidemiological data refers to the US, unless otherwise specified.

The underlying pathophysiology of POTS is complex and multifactorial. ^[2][3]

• Precipitating events ^[1][2][4]
  • Viral illness (e.g., COVID-19) ^[1][2]
  • Physical trauma (e.g., concussion)
  • Surgery
  • Adolescent growth spurt
  • Pregnancy
• Conditions associated with POTS
  • Hypermobile Ehlers-Danlos syndrome
  • Migraine headaches
  • Mast cell activation syndrome
  • Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) ^[5]
  • Fibromyalgia
  • Autoimmune diseases (e.g., Hashimoto thyroiditis, celiac disease)

POTS is a common manifestation of long COVID, affecting approx. 60% of patients. ^[6][7]

• Orthostatic symptoms, e.g.: ^[2][8]
  • Lightheadedness
  • Palpitations
  • Tremor
  • Generalized weakness
  • Blurred vision
• Nonorthostatic symptoms, e.g.: ^[1][2][4]
  • General: exercise intolerance, fatigue, sleep disturbance
  • Neurologic: headaches, cognitive dysfunction (e.g., impaired concentration, brain fog)
  • Gastrointestinal: nausea, bloating, diarrhea, and abdominal pain
  • Functional disability affecting daily activities, school, and work

Clinical features of POTS typically fluctuate over time and may have a relapsing and remitting pattern. ^[2]

Approach ^[2][4]

• Evaluate for diagnostic criteria for POTS in individuals with orthostatic symptoms that have persisted ≥ 3 months. ^[1][2]
  • Perform an active stand test for POTS or tilt table test. ^[2]
  • Obtain medication history for medications that cause orthostatic symptoms.
  • Assess for differential diagnoses of POTS.
    • Perform a thorough physical examination and obtain routine studies in all patients.
    • Consider additional studies in consultation with a specialist (e.g., cardiology, neurology) based on clinical presentation.
• Consider additional evaluation for conditions associated with POTS, as clinically indicated.

The diagnosis of POTS is typically delayed by years and initial misdiagnosis is common. ^[2][3]

Diagnostic criteria for POTS ^[1][2]

All criteria must be fulfilled to make the diagnosis.

• Orthostatic symptoms while standing that improve with lying down
• Symptoms present for ≥ 3 months
• Positive active stand test for POTS or tilt table test
• Absence of other causes of tachycardia (e.g., medications that cause orthostatic symptoms, differential diagnoses of POTS)

Active stand test for POTS ^[2][4]

• Timing and preparation
  • Perform in the morning.
  • Prior to test, the patient should:
    • Fast for ≥ 2 hours ^[2]
    • Rest supine for 5–10 minutes ^[2]
• Method
  • Measure baseline blood pressure and HR in supine position.
  • Repeat BP and HR at regular intervals for up to 10 minutes after standing (e.g., at 1, 3, 5, and 10 minutes). ^[4]
  • Document any symptoms experienced.
• Findings: A positive test must meet both of the following criteria.
  • Sustained increase in heart rate (HR) within 10 minutes of standing (on two measurements, at least one minute apart) ^[2][4][9]
    • Adults: increase in HR ≥ 30 bpm
    • Individuals 12–19 years of age: increase in HR ≥ 40 bpm
  • Absence of orthostatic hypotension

One negative active stand test does not rule out a diagnosis of POTS; consider repeat testing based on clinical suspicion. ^[2]

Routine studies ^[1][2][8]

• Blood tests
  • BMP: to assess for electrolyte disturbances or renal impairment
  • CBC: to evaluate for anemia
  • Thyroid function tests: to evaluate for hyperthyroidism
• ECG: to identify dysrhythmias

Additional studies ^[8][9]

Further evaluation in consultation with a specialist may be warranted based on clinical presentation and may include the following.

• Tilt table testing: to confirm the diagnosis if active stand test is inconclusive
• Cardiac testing
  • Holter monitor: to exclude conditions such as inappropriate sinus tachycardia, paroxysmal tachycardia (e.g., paroxysmal Afib, PSVT)
  • Evaluation for structural heart disease (e.g., transthoracic echocardiography, cardiac stress test)
• Plasma tryptase: to evaluate for mast cell activation syndrome if flushing is present in conjunction with tachycardia ^[4]

• Reflex syncope ^[4]
• Orthostatic hypotension
• Inappropriate sinus tachycardia
• Pheochromocytoma
• Anemia
• Hyperthyroidism
• Anxiety disorders (e.g., panic disorder)

The differential diagnoses listed here are not exhaustive.

The approach to management is similar in adults and children. ^[2]

General principles ^[2][9]

• POTS is typically not curable; therapy focuses on reducing symptoms and optimizing quality of life.
• Educate all patients on nonpharmacological management (e.g., increased water and salt intake, exercise).
• Pharmacological therapy (e.g., midodrine, fludrocortisone, and/or propranolol) is often required in addition to lifestyle modifications, especially for severe cases.
• Manage conditions associated with POTS (e.g., ME/CFS, mast cell activation syndrome).
• Refer to a specialist (e.g., cardiology, neurology) for severe or refractory features.

Specialist POTS care is limited; most patients are managed in primary care. ^[2][3]

Nonpharmacological management ^[2][4]

Educate patients on self-management strategies to improve circulating volume and venous return.

• Increased water intake (3 liters per day) and salt intake (10 g per day) ^[2]
• Avoidance of aggravating factors (e.g., heavy meals, alcohol intake, heat exposure)
• Abdominal and leg compression garments
• Personalized exercise therapy program (avoiding postexertional malaise) ^[2]
• Physical counterpressure maneuvers as needed (e.g., leg crossing, squatting)
• Sleeping with the head of the bed elevated 4–6 inches ^[2]

Pharmacological treatment ^[2][4]

• No medication is FDA-approved to treat POTS.
• The choice of agent is tailored to the clinical presentation and tolerability.
  • Consider medications that increase venous return for patients with:
    • Low BP when lying down
    • Evidence of hypovolemia
    • Lightheadedness as the predominant symptom
  • Consider medications that reduce heart rate for patients with:
    • High HR when lying down and/or high 24-hour average HR
    • Palpitations as the predominant symptom
• Titrate medications slowly and add additional medications one at a time if necessary. ^[9]