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Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO 2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O 2 saturation (SvO 2 ; susceptometry-based oximetry), and arterial O 2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO 2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO 2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose of Review: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations., Recent Findings: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Rapidly consuming water may offer practical orthostatic hypotension therapy. However, its efficacy across disorders remains uncertain. This study aims to assess the impact of rapid 350- to 500-mL water intake on systolic and diastolic blood pressure (BP) and heart rate (HR) through a systematic review and meta-analysis. Methods and Results We systematically reviewed MEDLINE and Embase up to June 2023, including randomized controlled trials and prospective cohort studies. Using random-effects meta-analysis, we calculated pooled mean differences (MDs) for maximum hemodynamic effects of rapid 350- to 500-mL water bolus consumption. Participants with orthostatic hypotension experienced increased systolic BP (MD, 24.18 [95% CI, 15.48-32.88]) and diastolic BP (MD, 11.98 [95% CI, 8.87-15.09]) with decreased HR (MD, -3.46 [95% CI, -5.21 to -1.71]). Similar results were observed in multiple system atrophy and pure autonomic failure subgroup analysis. Healthy participants showed modest increases in systolic BP (MD, 2.33 [95% CI, 1.02-3.64]) and diastolic BP (MD, 2.73 [95% CI, 1.15-4.30]), but HR changes were not significant (MD, -2.06 [95% CI, -5.25 to 1.13]). Water had no significant hemodynamic effects in patients with seated or supine postural tachycardia syndrome, although standing effects were unassessed. Our data do not exclude water's potential standing effect in postural tachycardia syndrome. Conclusions In patients with orthostatic hypotension, rapid water intake elevated short-term systolic BP and diastolic BP, with mild HR reduction when seated or supine. Healthy participants exhibited similar but milder effects. However, patients with postural tachycardia syndrome did not experience these changes in seated or supine positions. Further research is needed to evaluate the promising impact of rapid water ingestion on patients with postural tachycardia syndrome in a standing position, which was not addressed in our study.

Background: Many patients with postural orthostatic tachycardia syndrome (POTS) are hypovolemic with plasma volume deficits of 10-30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in angiotensin II, pointing to potential adrenal dysfunction. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and cortisol following adrenocorticotropin hormone (ACTH) stimulation., Methods: While on a low Na + diet (∼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 μg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 μg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h., Results: Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8-61.8 ng/dL] vs. 46.1 ng/dL [36.7-84.9 ng/dL]; P = 1.000) or maximally (56.4 ng/dL [49.2-67.1 ng/dL] vs. 49.5 ng/dL [39.1-82.8 ng/dL]; P = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 μg/dL [36.1-47.7 μg/dL] vs. 39.3 μg/dL [35.4-46.6 μg/dL]; P = 0.724) or maximally (39.9 μg/dL [33.9-45.4 μg/dL] vs. 42.0 μg/dL [37.6-49.7 μg/dL]; P = 0.354)., Conclusions: ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to hormonal stimulation is intact in patients with POTS., Competing Interests: Declaration of competing interest CAS has served as a consultant for Lundbeck NA Ltd. and Theravance RSS. IB has served as a consultant for Lundbeck NA Ltd., Theravance RSS, Ammeal Pharmaceuticals, Regeneron, and Takeda Pharmaceutical. Patent holder of automated binder for treatment of Orthostatic Hypotension. RSS is a Cardiac Arrhythmia Network of Canada (CANet) Network Investigator. SRR is a consultant to Lundbeck LLC, Theravance Biopharma Inc., and Amneal Pharma related to neurogenic orthostatic hypotension; Consultant to Servier Affaires Medicales, Regeneron, argenx BV, and Antag Pharma related to postural orthostatic tachycardia syndrome. Honoraria from Spire Learning and Medscape for developing CME materials on neurogenic orthostatic hypotension. DMSB Chair for a Phase 2 study of an irritable bowel syndrome medication for Arena Pharmaceuticals with compensation. Past-President of the American Autonomic Society without financial compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To evaluate the relationship between postural orthostatic tachycardia syndrome (POTS) and pregnancy., Design: Cross-sectional survey., Setting: International., Sample: A total of 8941 female patients with a diagnosis of POTS., Methods: Data from the survey were analysed using descriptive measures and stratified for comparisons., Main Outcome Measures: Symptom course of POTS during pregnancy. Secondary outcomes included pregnancy loss, POTS onset during pregnancy and the impacts of a comorbid diagnosis of Ehlers-Danlos syndrome or an autoimmune disorder on symptoms during pregnancy., Results: Overall, 40.8% (n = 3652) of participants reported one or more pregnancies. Most participants experienced worsening of symptoms in the first (62.6%) and third (58.9%) trimesters and 3 months after pregnancy (58.7%), and 81.1% experienced worsening symptoms at any point in their pregnancy. Most participants with worsening symptoms in the first trimester also experienced worsening symptoms in the second (61.6%) and third (68.1%) trimesters, but if they improved in the first trimester then this improvement persisted in the second and third trimesters. Of participants who reported that POTS was triggered by a specific event (41.3%), 8.1% reported pregnancy as the trigger for the onset., Conclusions: Postural orthostatic tachycardia syndrome symptoms in the first trimester of pregnancy may help predict symptom course throughout the duration of pregnancy. Some individuals may experience an initial onset of POTS during pregnancy. This novel information may guide clinicians in counselling patients with POTS who are planning pregnancy., (© 2023 John Wiley & Sons Ltd.)

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Background: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein-coupled receptors between patients with POTS and healthy controls., Methods: Sera were collected from 116 patients with POTS (91% female; medium age, 29 years) and 81 healthy controls (84% female; medium age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay., Results: Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls., Conclusions: Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay-derived autoantibody concentrations to cardiovascular G protein-coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.

Competing Interests: Competing interests: Satish Raj receives research support from the Canadian Institutes of Health Research (grant MOP142426), Dysautonomia International and the Vanderbilt Institute for Clinical and Translational Research, funded by a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences from the National Institutes of Health (UL1 TR000445). He reports consulting fees from Lundbeck, Theravance Biopharma and ArgenX BV, and payments and honoraria from Medscape, Spire Learning, Academy for Continued Healthcare Learning and Autonomic Neurosciences. He also reports payment for expert testimony from Faris Law, paid partipation on the data safety monitoring board for Arena Pharmaceuticals and unpaid participation on boards with the American Autonomic Society and the Canadian Cardiovascular Society Academy. Artur Fedorowski receives research support from Dysautonomia International. He reports consulting fees from ArgenX BV and payments and honoraria from Biotronick, Finapres Medical Systems and Bristol Myers Squibb. He also reports consulting fees, honoraria and participation on a data safety monitoring board with Medtronic. Robert Sheldon receives research support from the Canadian Institutes of Health Research and Dysautonomia International. He also reports 3 pending patents related to blood pressure monitoring and participation on a data safety monitoring board for a clinical trial on atrial fibrillation.

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Postural tachycardia syndrome (POTS), a syndrome characterized by orthostatic symptoms and a heart rate increase of at least 30 beats per minute in the absence of hypotension upon standing, is often accompanied by increased sympathetic activity and low blood volume. A common non-pharmacologic recommendation for patients with POTS is a high-sodium (HS) diet with the goal of bolstering circulating blood volume. The objective of this study is to assess the effects of 6 days of a HS diet on endothelial function in POTS., Methods: A total of 14 patients with POTS and 13 age-matched healthy controls, all females, were studied following 6 days on a low-sodium (LS) diet (10 mEq/day) and 6 days on a HS diet (300 mEq/day) in a crossover design. We measured endothelial function following reactive hyperemia in the brachial artery using flow-mediated dilation (FMD), leg blood flow (LBF) using strain gauge plethysmography in the calf, and reactive hyperemic index (RHI) in the microcirculation of the hand using pulsatile arterial tonometry., Results: On the LS diet, FMD% did not differ between patients with POTS and the healthy controls although peak brachial artery diameter was lower for the patient group. RHI was higher for the patient group than for the controls, but there were no differences in post-ischemic LBF increase. On the HS diet, there were no between-group differences in FMD%, LBF increase, or RHI., Conclusion: In summary, a HS diet for 6 days did not induce endothelial dysfunction. This non-pharmacologic treatment used for patients with POTS does not negatively affect endothelial function when used for a sub-acute duration., Trial Registration: ClinicalTrials.gov NCT01550315; March 9, 2012., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

Purpose: Postural tachycardia syndrome (POTS) and vasovagal syncope (VVS) are two disorders of orthostatic intolerance which are often misdiagnosed as the other. In each case, patients experience a reduced health-related quality of life (HRQoL) compared to healthy populations. This study was conducted to test the hypothesis that HRQoL is worse in POTS., Methods: POTS patients were recruited from the Dysautonomia International Annual Patient and Caregiver Conference. VVS patient data came from those enrolled in the Second Prevention of Syncope Trial. Participants aged ≥ 18 years (177 POTS and 72 VVS) completed the RAND 36-Item Health Survey, a generic and coherent health-related quality of life survey., Results: POTS patients reported reduced HRQoL compared to VVS patients in physical functioning (42.5 ± 1.7 vs. 76.5 ± 2.9, p < 0.001), role limitations due to physical health (11.4 ± 1.9 vs. 33.0 ± 5.0, p < 0.001), energy and fatigue (27.2 ± 1.3 vs. 50.7 ± 2.6, p < 0.001), social functioning (45.2 ± 1.8 vs. 71.2 ± 2.9, p < 0.001), pain (48.8 ± 1.9 vs. 67.7 ± 2.9, p < 0.001), and general health (31.2 ± 1.5 vs. 60.5 ± 2.6, p < 0.001) domains. Scores did not differ significantly in the role limitations due to emotional health (p = 0.052) and emotional well-being (p = 0.271) domains. Physical and general health composite scores were lower in the POTS population, while mental health composite scores were not different., Conclusion: Differences in HRQoL exist between these patient populations. POTS patients report lower scores in physical and general health domains than VVS patients, but emotional health domains do not differ significantly. Targeting physical functioning in these patients may help improve quality of life.

Background: High sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available., Objectives: This study tested whether a high sodium (HS) diet reduces orthostatic tachycardia (Δ heart rate) and upright heart rate compared with a low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine., Methods: A total of 14 POTS patients and 13 healthy control subjects (HC), age 23 to 49 years, were enrolled in a crossover study with 6 days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. Supine and standing heart rate, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine were measured., Results: In POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in HC on the HS diet (median 117 beats/min [interquartile range: 98 to 121 beats/min], 46 beats/min [interquartile range: 32 to 55 beats/min], and 753 pg/ml [interquartile range: 498 to 919 pg/ml] in POTS vs. 85 beats/min [interquartile range: 77 to 95 beats/min], 19 beats/min [interquartile range: 11 to 32 beats/min], and 387 pg/ml [interquartile range: 312 to 433 pg/ml] in HC, respectively), despite no difference in the measured PV., Conclusions: In POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases Δ heart rate. (Dietary Salt in Postural Tachycardia Syndrome; NCT01547117)., Competing Interests: Funding Support and Author Disclosures This work was supported in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R01 HL102387 and P01 HL056693, by the National Center for Advancing Translational Sciences Award UL1 TR000445, and the Vanderbilt Hormone & Analytical Services Core, which is supported by National Institutes of Health grants DK059637 and DK020593. Dr. Shibao has served as a consultant for Lundbeck NA Ltd. and Theravance RSS. Dr. Biaggioni has served as a consultant for Lundbeck NA Ltd. and Theravance RSS. Dr. Raj has served as a consultant for Lundbeck NA Ltd. and Theravance; has served as Chair of the Data Safety and Monitoring Board for Arena Pharmaceuticals and as Cardiac Arrhythmia Network of Canada Network Investigator; and has served on the Medical Advisory Board of Dysautonomia International and PoTS UK, both without financial compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Postural orthostatic tachycardia syndrome (POTS) and restless legs syndrome (RLS) are both characterized by sleep disturbance along with autoimmune/inflammatory features and autonomic dysfunction. However, to our knowledge, there has been no direct study looking at the prevalence of RLS in patients with POTS patients compared with healthy participants (controls)., Methods: Ninety-six physician-diagnosed patients with POTS (89 female and 7 male) and 130 controls (99 female and 31 male) were administered the Cambridge Hopkins questionnaire. Participants who were diagnosed with probable or definite RLS on the Cambridge Hopkins questionnaire were then contacted to determine the severity of RLS with the International Restless Legs Scale., Results: More patients with POTS (15 of 96; 15.6%) than controls (6 of 130; 4.6%) were diagnosed with probable or definite RLS on the Cambridge Hopkins questionnaire (P = .0048). A sensitivity analysis with only female respondents yielded similar results. RLS severity was in the moderate range (12.23 ± 9.22)., Conclusions: There is a higher prevalence of RLS in patients with POTS patients compared with controls. This association may have to do with shared increased inflammatory/autoimmune load and autonomic dysfunction., (© 2021 American Academy of Sleep Medicine.)

The purpose of this study is to evaluate endothelial function in postural tachycardia syndrome (PoTS), a poorly understood chronic condition characterized by a state of consistent orthostatic tachycardia (delta heart rate ≥30 beats per minute) upon standing without orthostatic hypotension. Nineteen patients with PoTS and 9 healthy controls were studied after 3 days of a fixed, caffeine-free, normal sodium (150 milliequivalents/day) diet. All participants underwent autonomic function testing, including sinus arrhythmia, valsalva maneuver, hyperventilation, cold pressor, handgrip, and a standing test with catecholamine measurements, followed by endothelial function testing. We analyzed 3 measures of endothelial function: percent brachial flow-mediated dilation, digital pulsatile arterial tonometry, and postischemic percent leg blood flow. Flow-mediated dilation was significantly lower in patients with PoTS (6.23±3.54% for PoTS) than in healthy controls (10.6±4.37% for controls versus, P =0.014). PoTS and controls had similar digital pulsatile arterial tonometry (1.93±0.40 arbitrary units for controls versus 2.13±0.63 arbitrary units for PoTS). PoTS had similar but suggestive percent leg blood flow to controls (313±158% for PoTS versus 468±236% for controls, P =0.098). Patients with PoTS have significantly reduced flow-mediated dilation compared with healthy controls, suggesting that PoTS is characterized by endothelial dysfunction in conduit arteries. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01308099.

Background: Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance associated with a significant symptom burden. Compression garments are a frequently prescribed treatment, but the effectiveness of waist-high compression has not been evaluated in adults with POTS., Objectives: This study evaluated compression garments as a treatment for POTS using a head-up tilt test (HUT), and a noninflatable core and lower body compression garment., Methods: Thirty participants completed 10-min HUT with each of 4 compression conditions in a randomized crossover design. The conditions were no compression (NONE), lower leg compression (LEG), abdominal/thigh compression (ABDO), and full abdominal/leg compression (FULL). Heart rate, beat-to-beat blood pressure, and Vanderbilt Orthostatic Symptom Score ratings were measured during each HUT., Results: The compression garment reduced heart rate (NONE: 109 ± 19 beats/min; LEG: 103 ± 16 beats/min; ABDO: 97 ± 15 beats/min; FULL: 92 ± 14 beats/min; p < 0.001) and improved symptoms (p < 0.001) during HUT in a dose-dependent manner. During HUT, stroke volume and systolic blood pressure were better maintained with FULL and ABDO compression compared with LEG and NONE compression., Conclusions: Abdominal and lower body compression reduced heart rate and improved symptoms during HUT in adult patients with POTS. These effects were driven by improved stroke volume with compression. Abdominal compression alone might also provide a clinical benefit if full lower body compression is not well tolerated. (Hemodynamic Effects of Compression in POTS; NCT03484273)., Competing Interests: Author Disclosures This study was supported by funding from the Libin Cardiovascular Institute. Ms. Kate Bourne is a Vanier Scholar supported by the Canadian Institutes of Health Research. Dr. Sheldon has been a network investigator for the Cardiac Arrhythmia Network of Canada. Dr. Exner has been a network investigator for the Cardiac Arrhythmia Network of Canada. Dr. Raj has been a consultant for Lundbeck NA Ltd. and Theravance Biopharma; has been the Chair of the Data Safety and Monitoring Board for Arena Pharmaceuticals; has been a network investigator for Cardiac Arrhythmia Network of Canada; and has been a member of the Medical Advisory Board of Dysautonomia International and PoTS UK, both without financial compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance associated with many GI manifestations that can be broadly classified into two different categories: those present all the time (non-positional) and those that occur with orthostatic position change. There are also many conditions that can co-exist with POTS such as mast cell activation syndrome and the hypermobile form of Ehlers-Danlos syndrome (hEDS) that are also oftentimes associated with GI symptoms. In the current issue of Neurogastroenterology and Motility, Tai et al. explored the relationship between functional GI disorders among hEDS patients with and without concomitant POTS and showed that the hEDS-POTS cohort was more likely to have more than one GI organ involved compared to the cohort with hEDS alone, and certain GI symptoms were also more common in the hEDS-POTS cohort. In this review article, we will briefly review the literature surrounding putative mechanisms responsible for GI symptoms in POTS with an emphasis on the contributory role of concomitant hEDS and then discuss management strategies for GI symptoms in POTS., (© 2020 John Wiley & Sons Ltd.)

Orthostatic hypotension (OH) is a common clinical manifestation characterized by a significant fall in blood pressure with postural change and is frequently accompanied by debilitating symptoms of orthostatic intolerance. The reported prevalence of OH ranges between 5 and 10% in middle-aged adults with a burden that increases concomitantly with age; in those over 60 years of age, the prevalence is estimated to be over 20%. Unfortunately, the clinical course of OH is not necessarily benign. OH patients are at an increased risk of adverse clinical outcomes including death, falls, cardiovascular and cerebrovascular events, syncope, and impaired quality of life. The differential diagnosis of OH is broad and includes acute precipitants as well as chronic underlying medical conditions, especially of neurological origin. Appropriate diagnosis relies on a systematic history and physical examination with particular attention to orthostatic vital signs, keeping in mind that ambient conditions during diagnostic testing may affect OH detection due to factors such as diurnal variation., Competing Interests: Declaration of competing interest SRR is a consultant to Lundbeck LLC and Theravance Biopharma related to neurogenic orthostatic hypotension, and has received honoraria from the Academy for Continued Healthcare Learning and Medscape for developing continuing medical educational materials about neurogenic orthostatic hypotension. He also serves as DMSB Chair for a Phase 2 study of an irritable bowel syndrome medication for Arena Pharmaceuticals with compensation. SRR is currently the President of the American Autonomic Society without financial compensation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Splanchnic venous pooling induced by upright posture triggers a compensatory increase in heart rate (HR), a response that is exaggerated in patients with postural tachycardia syndrome. To assess whether abdominal compression attenuates orthostatic tachycardia and improves symptoms, 18 postural tachycardia syndrome patients (32±2 years) were randomized to receive either abdominal compression (40 mm Hg applied with an inflatable binder ≈2 minutes before standing) or propranolol (20 mg) in a placebo-controlled, crossover study. Methods and Results Systolic blood pressure, HR, and symptoms were assessed while seated and standing, before and 2 hours postdrug. As expected, propranolol decreased standing HR compared with placebo (81±2 versus 98±4 beats per minute; P <0.001) and was associated with lower standing systolic blood pressure (93±2 versus 100±2 mm Hg for placebo; P =0.002). Compression had no effect on standing HR (96±4 beats per minute) but increased standing systolic blood pressure compared with placebo and propranolol (106±2 mm Hg; P <0.01). Neither propranolol nor compression improved symptoms compared with placebo. In 16 patients we compared the combination of abdominal compression and propranolol with propranolol alone. The combination had no additional effect on standing HR (81±2 beats per minute for both interventions) but prevented the decrease in standing systolic blood pressure produced by propranolol (98±2 versus 93±2 mm Hg for propranolol; P =0.029), and significantly improved total symptom burden (-6±2 versus -1±2 for propranolol; P =0.041). Conclusions Splanchnic venous compression alone did not improve HR or symptoms but prevented the blood pressure decrease produced by propranolol. The combination was more effective in improving symptoms than either alone. Splanchnic venous compression can be a useful adjuvant therapy to propranolol in postural tachycardia syndrome. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00262470.

The current definition of postural orthostatic tachycardia syndrome (POTS) dates back to a small case series of patients with a subacute illness who presented with excessive orthostatic tachycardia and orthostatic intolerance, in the absence of another recognized disease. Conventional POTS criteria require an excessive orthostatic tachycardia in the absence of substantial orthostatic hypotension, and predominant symptoms of orthostatic intolerance, worse with upright posture and better with recumbence. POTS is a heterogeneous syndrome with likely several underlying pathophysiological processes, and not a specific disease. The primary panel for this Canadian Cardiovascular Society position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, and developed recommendations on the basis of the Canadian Cardiovascular Society approach to position statements. One identified problem was that numerous patients who did not meet criteria for POTS would still be given that diagnoses by providers to validate the illness even though this diagnosis is incorrect. This includes patients with postural symptoms without tachycardia, orthostatic tachycardia without symptoms, and those with orthostatic tachycardia but another overt cause for excessive tachycardia. We developed a novel nomenclature ecosystem for orthostatic intolerance syndromes to increase clarity. We also provide more clarity on how to interpret the orthostatic vital signs. These concepts will need to be prospectively assessed., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension. The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Patients often will exhibit overlapping characteristics from more than one of these mechanisms. The approach to the treatment of POTS centers on treating the underlying pathophysiologic mechanism. Stockings, abdominal binders, and vasoconstrictors are used to enhance venous return in partial neuropathic POTS. Exercise and volume expansion are the main treatment strategies for hypo-volemic POTS. For hyperadrenergic POTS, beta-blockers and avoidance of norepinephrine reuptake inhibitors is important. Attempts should be made to discern which pathophysiologic mechanism(s) may be afflicting patients so that treatment regimens can be individualized.

The diagnosis of neuropathic postural tachycardia syndrome (POTS) requires research techniques not available clinically. We hypothesized that these patients will have impaired vagal and sympathetic cardiovascular control that can be characterized with clinical autonomic tests. We included 12 POTS patients with possible neuropathic subtype because of normal plasma norepinephrine and no increase in upright blood pressure. We compared them to 10 healthy subjects. We assessed hemodynamics, heart rate and blood pressure variability, baroreflex sensitivity, raw and integrated muscle sympathetic nerve activity, and blood volume. To understand the vagal/sympathetic control, we dissected the phase 2 of Valsalva maneuver (VM) into early (VM2e) and late (VM2l). POTS' upright heart rate increased 43±3 bpm. Patients had normal plasma volume but reduced red blood cell volume (1.29 L versus predicted normal values 1.58 L; P=0.02). Vagal indices of heart rate variability, HF RRI (430±130 versus 1680±900; P=0.04), PNN50, and root mean squared of successive differences were lower in POTS. Patients showed a decrease in vagal baroreflex sensitivity (VM2e; P=0.04). In POTS, integrated muscle sympathetic nerve activity was lower at rest (12±1.5 versus 20±2 burst/min; P=0.004) and raw muscle sympathetic nerve activity spike analysis showed blunted responses during VM2e, despite a greater drop in systolic blood pressure (34±5 in POTS and 14±6 mm Hg in controls; P=0.01). This cohort of POTS patients enriched for possible neuropathic subtype had lower resting muscle sympathetic nerve activity, impaired vagal cardiac control, and exaggerated drop in blood pressure in response to VM and a delay in the sympathetic cardiovascular responsiveness during hypotensive challenge.

Postural tachycardia syndrome (POTS) is a disorder of the autonomic nervous system with many possible causes, characterized by an unexplained increase in heartbeat without change in blood pressure upon standing. Associated cardiac and noncardiac symptoms can severely affect quality of life. Therapy, using a combined approach of diet and lifestyle changes, plus judicious use of medications if needed, can usually improve symptoms and function., (Copyright © 2019 Cleveland Clinic.)

Postural Tachycardia Syndrome (POTS) is a multi-system disorder that can be associated with significant functional disability. Likely due to the multi-system nature of the disorder, it can be difficult for physicians caring for these patients with POTS to know enough about the management of problems that fall within so many different specialties. This special issue was written for these clinicians and their patients. We have brought together experts on POTS with different backgrounds to share their approach to many of the medical issues that confront patients with POTS. The result is this special POTS Issue of Autonomic Neurosciences that can serve as a "User's Guide to POTS"., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Our understanding about Postural Tachycardia Syndrome (POTS) has advanced significantly over the last 25 years. Despite the significant advances that have been made in defining the syndrome and finding some treatments for our patients, there is much work to be done to significantly improve our understanding of the disorder and improve therapeutics. In this article, 5 NEEDS are identified that will be required over the next several years if we want future care to move beyond where we are in the present. These include: (1) a NEED for better administrative data to track POTS diagnoses and the impact of the illness; (2) a NEED to improve physician awareness about POTS, which is a prerequisite for improved access to care; (3) a NEED to better understand the multiple pathophysiologies underlying POTS and the roles of the different medical comorbidities; (4) a NEED for data on effective treatments for POTS; and (5) a NEED for more research funding to study POTS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Postural tachycardia syndrome (POTS) is a heterogeneous clinical syndrome that has gained increasing interest over the past few decades due to its increasing prevalence and clinical impact on health-related quality of life. POTS is clinically characterized by sustained excessive tachycardia upon standing that occurs in the absence of significant orthostatic hypotension and other medical conditions and or medications, and with chronic symptoms of orthostatic intolerance. POTS represents one of the most common presentations of syncope and presyncope secondary to autonomic dysfunction in emergency rooms and in cardiology, neurology, and primary care clinics. The most sensitive method to detect POTS is a detailed medical history, physical examination with orthostatic vital signs or brief tilt table test, and a resting 12-lead electrocardiogram. Additional diagnostic testing may be warranted in selected patients based on clinical signs. While the precise etiology remains unknown, the orthostatic tachycardia in POTS is thought to reflect convergence of multiple pathophysiological processes, as a final common pathway. Based on this, POTS is often described as a clinical syndrome consisting of multiple heterogeneous disorders, with several underlying pathophysiological processes proposed in the literature including partial sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, and immune-mediated. These clinical features often overlap, however, making it difficult to categorize individual patients. Importantly, POTS is not associated with mortality, with many patients improving to some degree over time after diagnosis and proper treatment. This review will outline the current understanding of diagnosis, pathophysiology, and prognosis in POTS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and β1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS., Methods and Results: Serum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1-adrenergic receptor., Conclusions: Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aims: Postural Tachycardia Syndrome (POTS) represents an autonomic disorder predominantly affecting females between 15 and 50 years of age. POTS is a chronic disorder (>6 months) characterized by an excessive heart rate increment on standing (>30 beats/min) in the presence of characteristic symptoms of cerebral hypoperfusion or sympathetic activation. Patients have clinically been noted to describe lower urinary tract symptoms (LUTS), although urologic symptoms have not been methodically assessed in the POTS population. Herein, we present data from a pilot study designed to identify and quantitate overactive bladder (OAB) in patients diagnosed with POTS., Methods: Patients admitted to the Vanderbilt Autonomic Dysfunction Center between June 2009 and October 2010 for evaluation for the potential diagnosis of POTS completed a validated, standardized questionnaire for OAB (OAB-q) at presentation. Symptom score and subscale analyses were conducted. Subscale health related quality of life (HRQL) scores were transformed into a 0-100 scale, with higher scores reflecting superior HRQL. Data are presented as mean ± SD., Results: Thirty-two females presented for evaluation of symptoms consistent with POTS. Twenty-nine women were subsequently diagnosed with POTS with 19 of these patients completing the OAB-q questionnaire (65.5% response rate). Average age was 33.5 ± 8.3 years. Symptom severity transformed score was 26.0 ± 16.4, with 13 of 19 patients (68.4%) meeting clinical criteria for diagnosis of probable clinically significant OAB. Nocturia was the most bothersome symptom, followed by increased daytime frequency and urgency., Conclusions: This pilot study describes bothersome lower urinary tract dysfunction in patients presenting with POTS as assessed by patient-reported questionnaire data. Nocturia demonstrated the greatest negative impact on health-related quality of life (HRQL), while social interaction was the least affected HRQL domain. In patients with dysautonomia, this data provides a critical baseline for mechanistic insight into both disease-specific and global pathophysiology of nocturia and OAB. Neurourol. Urodynam. 36:610-613, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Postural tachycardia syndrome (POTS) is a multifactorial clinical syndrome defined by an increase in heart rate of ≥30 bpm on standing from supine position (or ≥40 bpm in children). It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve when in supine position. Patients often have additional symptoms including severe fatigue and difficulty concentrating. There are several possible pathophysiologic mechanisms including hypovolaemia, small-fibre peripheral neuropathy and hyperadrenergic states. POTS can also be associated with several disorders including mastocytosis, Ehlers-Danlos syndrome (hypermobility type) and autoimmune disorders. The treatment is focused on symptom relief and not solely on reducing tachycardia. Given its varying presentations, it is important to employ a practical, mechanism-focused approach to the diagnosis and management of POTS., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Study Objectives: Patients with postural tachycardia syndrome (POTS) commonly complain of fatigue, unrefreshing sleep, daytime sleepiness, and diminished quality of life. The study objective was to assess objective sleep quality in POTS patients using overnight polysomnography., Methods: We studied 16 patients with POTS and 15 healthy control subjects performing daytime autonomic functions tests and overnight polysomnography at the Vanderbilt Clinical Research Center., Results: There were no significant differences in the objective sleep parameters including sleep efficiency, sleep onset latency, wake time after sleep onset, REM latency, percentage of time spent in N1, N2, N3, and REM sleep, arousal index, apnea-hypopnea index, or periodic leg movement index in POTS patients as compared with healthy control subjects. There were significant negative correlations between sleep efficiency and the change in HR from supine to stand (rs = -0.527; p = 0.036)., Conclusions: POTS patients do not have significant differences in objective sleep parameters as compared to control subjects based on overnight polysomnograms. Activation of the sympathetic nervous system may contribute significantly to the hyper arousal state and worsening of subjective estimates of sleep quality as previously reported in POTS patients., (© 2016 American Academy of Sleep Medicine.)

Sympathetic activation is thought to contribute to the inflammatory process associated with obesity, which is characterized by elevated circulating C-reactive protein (hsCRP) and interleukin-6 (IL-6). To evaluate whether sympathetic activation is associated with inflammation in the absence of obesity, we studied patients with postural tachycardia syndrome (POTS), a condition characterized by increased sympathetic tone in otherwise healthy individuals. Compared with 23 lean controls, 43 lean female POTS had greater vascular sympathetic modulation (low-frequency blood pressure variability, LFSBP, 3.2 ± 0.4 vs. 5.5 ± 0.6 mmHg(2), respectively, P = 0.006), lower cardiac parasympathetic modulation (high-frequency heart rate variability, 1,414 ± 398 vs. 369 ± 66 ms(2), P = 0.001), and increased serum IL-6 (2.33 ± 0.49 vs. 4.15 ± 0.54 pg/ml, P = 0.011), but this was not associated with increases in hsCRP, which was low in both groups (0.69 ± 0.15 vs. 0.82 ± 0.16 mg/l, P = 0.736). To explore the contribution of adiposity to inflammation, we then compared 13 obese female POTS patients and 17 obese female controls to matched lean counterparts (13 POTS and 11 controls). Compared with lean controls, obese controls had increased LFSBP (3.3 ± 0.5 vs. 7.0 ± 1.1 mmHg(2); P = 0.016), IL-6 (2.15 ± 0.58 vs. 3.92 ± 0.43 pg/ml; P = 0.030) and hsCRP (0.69 ± 0.20 vs. 3.47 ± 0.72 mg/l; P = 0.001). Obese and lean POTS had similarly high IL-6 but only obese POTS had increased hsCRP (5.76 ± 1.99 mg/l vs. 0.65 ± 0.26; P < 0.001). In conclusion, sympathetic activation in POTS is associated with increased IL-6 even in the absence of obesity. The coupling between IL-6 and CRP, however, requires increased adiposity, likely through release of IL-6 by visceral fat., (Copyright © 2015 the American Physiological Society.)

Postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a "final common pathway" for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support.

Background: The objective of this study was to determine the effect of inspiratory resistance through an impedance threshold device (ITD) on orthostatic tolerance in patients with postural tachycardia syndrome. We hypothesized that the ITD would result in a greater negative intrathoracic pressure to enhance cardiac venous return, improve stroke volume, and reduce heart rate in these patients., Methods and Results: We compared the effect of a sham device (sham, no resistance) versus an ITD (increased inspiratory resistance) in 26 patients with postural tachycardia syndrome in a randomized, single-blind, crossover study. Hemodynamic assessments were performed at baseline while supine and during head-up tilt to 70° for 10 minutes. We did not find differences in baseline hemodynamic parameters between the ITD and the sham devices. After 10 minutes of head-up tilt, the heart rate was lower with the ITD versus sham device (102±4 versus 109±4 beat/min, respectively; P=0.003). The ITD also improved stroke volume compared with the sham device (35±2 versus 26±1 mL; P=0.006)., Conclusions: These findings suggest that increasing negative intrathoracic pressure with ITD breathing improves heart rate control in patients with postural tachycardia syndrome during upright posture., Clinical Trial Registration: clinicaltrials.gov; Unique Identifier: NCT00962728., (© 2015 American Heart Association, Inc.)

Mental clouding is an almost universal complaint among patients with postural tachycardia syndrome (POTS) but remains poorly understood. Thus, we have determined whether POTS patients exhibit deficits during neuropsychological testing relative to healthy subjects. A comprehensive battery of validated neuropsychological tests was administered to 28 female POTS patients and 24 healthy subjects in a semi-recumbent position. Healthy subjects were matched to POTS patients on age and gender. Selective attention, a primary outcome measure, and cognitive processing speed were reduced in POTS patients compared with healthy subjects (Ruff 2&7 Speed t-score: 40±9 compared with 49±8; P=0.009; Symbol Digit Modalities Test t-score: 45±12 compared with 51±8; P=0.011). Measures of executive function were also lower in POTS patients (Trails B t-score: 46±8 compared with 52±8; P=0.007; Stroop Word Color t-score: 45±10 compared with 56±8; P=0.001), suggesting difficulties in tracking and mental flexibility. Measures of sustained attention, psychomotor speed, memory function or verbal fluency were not significantly different between groups. The present study provides evidence for deficits in selective attention and cognitive processing in patients with POTS, in the seated position when orthostatic stress is minimized. In contrast, other measures of cognitive function, including memory assessments, were not impaired in these patients, suggesting selectivity in these deficits. These findings provide new insight into the profile of cognitive dysfunction in POTS and provide the basis for further studies to identify clinical strategies to better manage the mental clouding associated with this condition.

Background: Postural tachycardia syndrome (POTS) is characterized clinically not only by an exaggerated increase in heart rate (HR), but an associated cognitive impairment that disables many patients. Modafinil might be effective in improving the cognitive symptoms, but modafinil may stimulate the sympathetic nervous system and worsen tachycardia in POTS. We tested the hypothesis that modafinil would worsen tachycardia and orthostatic symptoms in POTS., Methods: Patients with POTS (n = 54) underwent a randomized crossover trial with modafinil 100 mg versus placebo. Heart rate and systolic blood pressure (SBP) were measured seated and standing before modafinil or placebo administration and then hourly for 4 hours., Results: Over 4 hours, standing HR was not significantly different between the modafinil and placebo groups (analysis of variance [ANOVA] Pdrug = 0.328), but seated SBP was significantly higher in the modafinil group (mean [SD], 109 [12] mm Hg vs 104 [10] mm Hg; P = 0.004). Modafinil also significantly increased both the seated SBP (ANOVA Pdrug = 0.004) and the standing SBP (ANOVA Pdrug = 0.041) over time. There was no significant difference between modafinil and placebo over the 4-hour period with regard to POTS symptom burden scores (14 [12] vs 14 [12]; P = 0.962)., Conclusions: Modafinil did not significantly worsen standing HR or acute orthostatic symptoms in patients with POTS compared with the placebo group and improved upright blood pressure. Therefore, modafinil could be tested as a potential treatment for the cognitive impairment in POTS.

Postural tachycardia syndrome (POTS) is associated with exercise intolerance, hypovolemia, and cardiac atrophy, which may contribute to reduced stroke volume and compensatory exaggerated heart rate (HR) increases. Acute volume loading with intravenous (iv) saline reduces HR and improves orthostatic tolerance and symptoms in POTS, but its effect on exercise capacity is unknown. In this study, we determined the effect of iv saline infusion on peak exercise capacity (VO2peak) in POTS. Nineteen patients with POTS participated in a sequential study. VO2peak was measured on two separate study days, following administration of placebo or 1 liter of i.v. saline (NaCl 0.9%). Patients exercised on a semirecumbent bicycle with resistance increased by 25 W every 2 min until maximal effort was achieved. Patients exhibited blood volume deficits (-13.4 ± 1.4% ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline significantly increased stroke volume (saline 80 ± 8 ml vs. placebo 64 ± 4 ml; P = 0.010), increased cardiac output (saline 6.9 ± 0.5 liter/min vs. placebo 5.7 ± 0.2 liter/min; P = 0.021), and reduced systemic vascular resistance (saline 992.6 ± 70.0 dyn-s/cm(5) vs. placebo 1,184.0 ± 50.8 dyn-s/cm(5); P = 0.011), with no effect on HR or blood pressure. During exercise, saline did not produce differences in VO2peak (saline 26.3 ± 1.2 mg·kg(-1)·min(-1) vs. placebo 27.7 ± 1.8 mg·kg(-1)·min(-1); P = 0.615), peak HR [saline 174 ± 4 beats per minute (bpm) vs. placebo 175 ± 3 bpm; P = 0.672] or other cardiovascular parameters. These findings suggest that acute volume loading with saline does not improve VO2peak or cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function., (Copyright © 2014 the American Physiological Society.)

Background: Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate (HR) upon standing, and many POTS patients have a hyperadrenergic state. Medications that restrain HR are a promising approach to this problem., Objective: We tested the hypothesis that melatonin will attenuate the tachycardia and improve symptom burden in patients with POTS., Methods: Patients with POTS (n = 78) underwent acute drug trials with melatonin 3 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, HR, and symptoms were assessed while seated and after standing for up to 10 min prior to, and hourly for 4 h following study drug administration., Results: The reduction in standing HR was significantly greater 2 h after melatonin compared with placebo (P = 0.017). There was no significant difference in the reduction of systolic blood pressure between melatonin and placebo, either with standing or while seated. The symptom burden was not improved with melatonin compared with placebo., Conclusion: Oral melatonin produced a modest decrease in standing tachycardia in POTS. Further research is needed to determine the effects of regular night-time use of this medication in POTS., (© 2014 John Wiley & Sons Ltd.)