Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1

Abstract

Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.

Keywords: Expert consensus; Pathophysiology; Postural orthostatic tachycardia syndrome; Treatment; Workshop.

Fig. 1.

Schematic of possible mechanisms leading to orthostatic intolerance and tachycardia in POTS. During upright posture, there is a gravitational shift of plasma volume toward the lower parts of the body which if unopposed would result in reduced cardiac preload and a fall in blood pressure. The autonomic baroreflex serves to prevent orthostatic hypotension and preserve cardiac output through sympathetic activation (peripheral vasoconstriction and increased heart rate). In POTS, excessive orthostatic tachycardia may result from a combination of appropriate autonomic responses to various physiological changes (shown in blue) or an inappropriate exaggeration of the sympathetic response to orthostatic stress (shown in red). Abnormal cardiovascular physiology could include (1) absolute hypovolemia due to impaired regulation of plasma volume or (2) cardiovascular deconditioning resulting in reduced cardiac mass and low stroke volume. Excessive sympathetic activation may occur in the context of (3) a systemic inflammatory state with increased inflammatory mediators (for example, increased histamine in conditions of mast cell overactivity) or (4) increased sympathetic tone driven by central nervous system (e.g. anxiety or chronic pain). Autoantibodies targeting G-protein coupled autonomic receptors (5) could produce mixed effects by acting as partial agonists that both augment cardiac sympathetic signals and reduce the efficacy of norepinephrine-induced peripheral vasocontriction. Finally, abnormal peripheral vascular function may result from (6) peripheral small fiber neuropathy causing partial denervation in the lower extremities or (7) tissue laxity resulting in increased dependent venous pooling (which might explain an association of POTS with hEDS). RAAS = renin-angiotensin-aldosterone system; MCAS = mast cell activation syndrome; AAbs = autoantibodies; hEDS = hypermobile form of Ehlers-Danlos syndrome. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)