Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a syndrome of an exaggerated heart rate (HR) response with standing, disproportionately affecting young women associated with exercise intolerance due to dizziness, palpitations, and/or chest pain. Research question: How does the exaggerated increase in HR with standing translate into impaired exercise tolerance in subjects with POTS? Aims: To systematically analyze determinants of exercise intolerance in subjects with POTS. Methods: We searched the National Library of Science and identifed 11 cohorts with a diagnosis of POTS and an assessment of exercise capacity. We abstracted the information including type of exercise testing, hemodynamics and gas exchange parameters (peak oxygen consumption [VO 2 ]) with exercise, and effect of interventions (if present). Results: We identified 849 subjects with POTS, female:male ratio of 8.5:1, 25±8 years, and 365 age-and sex-matched controls. A cycle ergometer was used in 8 studies (574 subjects, 68%) and a treadmill in 3 (275 subjects, 32%). Peak VO 2 was measured in 10 studies (836 subjects, 98%), and exercise hemodynamics in 9 (593 subjects, 70%). All 11 (100%) studies described a higher HR at rest and during submaximal exercise in subjects with POTS, with a similar slope of HR/load, and shorter time to peak HR. Of the 9 studies with hemodynamics, 6 (67%) reported a reduction in stroke volume (SV) with standing and with exercise, but only 1 (11%) documented a reduction in cardiac output (CO). Two studies (22%) enrolling teenagers showed a variable increase in SV and CO in POTS. Peak VO 2 was reduced in 8 (80%) studies when compared with predicted values, but only in 4 (40%) when compared with controls matched for deconditioning. Intravenous fluid administration in two studies did not affect HR, SV, CO or peak VO 2 . Exercise training in one study (19 subjects) and propranolol 20 mg in another study (11 subjects) led to improving peak VO 2 . Conclusions: An exaggerated HR response with standing and with exercise is a hallmark of POTS, a mechanism by which subjects reach a higher HR at lower workloads. While the increase in HR is associated with a reduction in SV, CO is typically maintained and occasionally increased, therefore making it an unlikely mechanism responsible for the peculiar exertional symptoms of POTS. Strategies that result in a reduction in HR may, on the other hand, translate in improved exercise capacity in subjects with POTS.
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