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Research Request – Postural Orthostatic Tachycardia Syndrome

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Research Request – Postural Orthostatic Tachycardia Syndrome

Brief Known available and appropriate evidence based clinical, medical or other treatments for Postural Orthostatic Tachycardia Syndrome
Date 05/10/2020
Requester Wendy s47F - perso (Assistant Director TAB) Naomi s47F - personal pr (Senior Technical Advisor TAB)
Researcher Jane s47F - personal priv (Research Team Leader TAB)

Contents

  • Summary … 2
  • What is Postural Orthostatic Tachycardia Syndrome? … 2
  • Diagnostic criteria … 2
  • Clinical presentation … 3
  • Management … 4
  • Reference List … 6

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Summary

  • Postural Orthostatic Tachycardia Syndrome (POTS) is a variant of cardiovascular autonomic disorder characterised by orthostatic intolerance and abnormal heart rate response on standing associated with symptoms of deconditioning, cognitive impairment and a myriad of unspecific symptoms
  • The aetiology of POTS is unknown and predominantly effects young females
  • Patient education is key to managing the symptoms of POTS
  • Exercise training and acute saline infusion are the only treatments with Class IIA recommendations (‘should be considered’)
  • Other treatments that ‘may be considered’ include:
    • Increased fluid and salt intake
    • Midodrine
    • Beta-blockers
    • Fludrocortisone
    • Pyridostigmine, clonidine
    • Alpha-methyldopa

What is Postural Orthostatic Tachycardia Syndrome?

Postural orthostatic tachycardia syndrome (POTS) is a common, although not so well-known variant of cardiovascular autonomic disorder. It is characterised by an excessive heart rate increase on standing, symptoms of orthostatic intolerance and occasional syncope. 1, 2 The syndrome affects younger individuals, with a distinct predominance of women (>80%). 3, 4 The prevalence estimates are imprecise and range between 0.2% and 1.0% based on statistics from the United States. 3, 4

The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. 5-13 The aetiology of POTS is largely unknown, however, there are three main hypotheses which include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. 14

Diagnostic criteria

The current diagnostic criteria for POTS is summarised in Table 1 below and has been endorsed by the American Academy of Neurology, American Autonomic Society, American College of Cardiology, American Heart Association, European Federation of Autonomic Societies, European Heart Rhythm Association, European Society of Cardiology and Heart Rhythm Society. 1, 3, 15, 16

Table 1: Diagnostic criteria of postural orthostatic tachycardia syndrome

Sustained heart rate increment of not less than 30 beats min or above 120 beats min within 10 min of active standing or head-up tilt

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Clinical presentation

A characteristic patient with POTS is a young woman approximately 25 years of age, reporting first symptoms at around 15 years, although the range of disease onset may extend until the fifth decade of life and 20% are men. Common clinical symptoms of POTS can be found in Table 2.

Table 2 Clinical presentation of POTS

Cardiovascular system Main: Orthostatic intolerance, orthostatic tachycardia, palpitations, dizziness, light-headedness, Pre-syncope, exercise intolerance
Other frequent symptoms: dyspnoea, chest pain/discomfort, acrocyanosis, Raynaud’s phenomenon, venous pooling, limb oedema

| General symptoms | General deconditioning, chronic fatigue, exhaustion, heat intolerance, fever, debility, bedridden |

| Nervous system | Headache/migraine, mental clouding (‘brain fog’), cognitive impairment, concentration problems, anxiety, tremulousness, light and sound sensitivity, blurred/tunnel vision, neuropathic pain (regional), sleeping disorders, involuntary movements |

| Musculoskeletal system | Muscle fatigue, weakness, muscle pain |

| Gastrointestinal system | Nausea, dysmotility, gastroparesis, constipation, diarrhoea, abdominal pain, weight loss |

| Respiratory system | Hyperventilation, bronchial asthma, shortness of breath |

| Urogenital system | Bladder dysfunction, nycturia, polyuria |

| Skin | Petechiae, rashes, erythema, telangiectasias, abnormal sudomotor regulation, diaphoresis, pallor, flushing |

Management

The heterogeneity and wide spectrum of POTS related symptoms create a great challenge for clinicians and affected patients. Moreover, poorly explored pathophysiology of POTS makes it literally impossibly to treat the root cause of the disease and the management of POTS is usually focused on symptom alleviation. 17, 18 The long-term prognosis of POTS is not well explored. It is estimated that around 50% of all POTS patients spontaneously recover within 1–3 years. 15

Once a diagnosis has been made, patients should be thoroughly educated about non-pharmacological measures to alleviate symptoms, long term prognosis and available therapeutic options (see Table 3). It should be noted that large randomized trials investigating POTS treatments are not available 19 and there are no Class I (is recommended) recommendations to date. 3 The only Class IIA (should be considered) recommendations are exercise training against chronic symptoms and acute saline infusion in decompensated POTS 3 both lead to positive effects on plasma volume. 20 Among Class IIB (may be considered) recommendations are increased fluid and salt intake, midodrine, beta-blockers, fludrocortisone, pyridostigmine, clonidine and alpha-methyldopa. 3, 19, 21

Therapy Comments
Non-pharmacological treatment This point is crucial and should form the fundament of treatment. 3 It is rarely sufficient alone in pronounced symptoms. Patients and their families should understand the basics of orthostatic physiology and importance of non-pharmacological methods.
  • Understanding of orthostatic intolerance and POTS pathophysiology
  • Avoidance of immobilisation, prolonged lying down and physical deconditioning
  • Gradual rising from supine and sitting position, especially in the morning, after meals, and after urination/defecation
  • Small and frequent instead of large meals
  • Avoidance of prolonged standing, high ambient temperature and high humidity
  • Physical counter-manoeuvres (leg crossing, muscle tensing, squatting, etc.) during standing and prodromal symptoms 22, 23 | Educational materials such as brochures, instruction films may be very helpful | | Exercise Training | A regular, structured, graduated, and supervised exercise programme featuring aerobic reconditioning with some resistance training for the thighs is preferable. Initial training should avoid upright position. Mild-to moderate- intensity endurance training, progressing from semi recumbent to upright position plus strength training is recommended. Rowing machines, recumbent bicycles and swimming may be applied. 3, 24, 25 | |

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| Increased salt and fluid intake including oral water bolus if needed | A daily dietary intake of more than 10 g of sodium per day or salt tablets (e.g. 1g 3x day) and a fluid intake of at least 2.5 litre per day is recommended. 3, 26 | | Compression stockings/garments | Reduction of peripheral pooling in the lower limbs and splanchnic region.

Class 2 compression garments (>30 mmHg) are recommended. 3, 26, 27 They might be considered in the ‘hypovolemic’ subtype and low-BP phenotype. Especially, when venous pooling is observed or suspected | | Pharmacological treatments | | Heart rate controlling agents | | Beta-blockers | Beta-blockers are especially recommended in ‘hyper adrenergic’ subtype associated with sinus tachycardia >120 bpm on standing.

Beta-blockers may aggravate orthostatic intolerance in low-BP phenotype, asthma and paroxysmal chest pain. 3, 26, 28, 29 | | Ivabradine | This drug is effective in low-BP phenotype or when beta-blockers are not well tolerated. It is usually seen as an alternative to beta-blockers. The evidence is based on small patient series. 30 | | Verapamil | Can be tested in ‘hyper adrenergic’ type associated with higher BP, migraine, and chest pain. The evidence and clinical experience are very limited. 31 | | Vasoactive and volume-expanding agents | | Clonidine | Generally recommended for ‘hyper adrenergic’ subtype and hypertensive tendency on standing. 3, 17, 32 | | Midodrine | One of the few pharmacological agents positively tested in placebo-controlled studies for orthostatic hypotension. It may be effective in ‘hypovolemic’ subtype and low-BP phenotype with pronounced orthostatic intolerance. 3, 28, 29, 33, 34 | | Droxdopa | Drug has been empirically used off label in severe POTS. Not included in the current guidelines. 28 | | Pyridostigmine | May be considered in POTS phenotype associated with suspected autonomic neuropathy, gastrointestinal dysfunction and non-specific muscle weakness. Effect on BP is small. 3, 35, 36 | | Fludrocortisone | Increases sodium reabsorption and enhances sensitivity of alpha adrenoreceptors. May |

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Reference List

  • Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clinical Autonomic Research. 2011 Apr 1;21(2):69-72.

  • Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. InMayo Clinic Proceedings 2012 Dec 1 (Vol. 87, No. 12, pp. 1214-1225). Elsevier.

  • Sheldon RS, Grubb BP, Olshansky B, Shen WK, Calkins H, Brignole M, Raj SR, Krahn AD, Morillo CA, Stewart JM, Sutton R. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart rhythm. 2015 Jun 1;12(6):e41-63.

  • Arnold AC, Ng J, Raj SR. Postural tachycardia syndrome—diagnosis, physiology, and prognosis. Autonomic Neuroscience. 2018 Dec 1;215:3-11.

  • Low PA, Opfer-Gehrking TL, Textor SC et al. Postural tachycardia syndrome (POTS). Neurology 1995; 45: S19–25.

  • Thieben MJ, Sandroni P, Sletten DM et al. Postural orthostatic tachycardia syndrome: the Mayo clinic experience. Mayo Clin Proc 2007; 82: 308–13.

  • Sandroni P, Opfer-Gehrking TL, McPhee BR, Low PA. Postural tachycardia syndrome: clinical features and follow-up study. Mayo Clin Proc 1999; 74: 1106–10.

  • Brinth LS, Pors K, Theibel AC, Mehlsen J. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus. Vaccine 2015; 33: 2602–5.

  • Blitshteyn S, Brook J. Postural tachycardia syndrome (POTS) with anti-NMDA receptor antibodies after human papillomavirus vaccination. Immunol Res 2016; 65: 282–4.

  • Watari M, Nakane S, Mukaino A et al. Autoimmune postural orthostatic tachycardia syndrome. Ann Clin Transl Neurol 2018; 5: 486–92.

  • 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.

  • Schofield JR, Hendrickson JE. Autoimmunity, autonomic neuropathy, and the HPV vaccination: a vulnerable subpopulation. Clin Pediatr (Phila) 2018; 57: 603–6.

  • Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol 2014; 21: 135–9.

  • Fedorowski A. Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management. Journal of internal medicine. 2019 Apr; 285(4):352-66.

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