This article reviews the diagnosis and management of the most common disorders of orthostatic intolerance: postural tachycardia syndrome (POTS) and neurally mediated syncope. POTS is a heterogeneous syndrome caused by several pathophysiologic mechanisms that may coexist (limited autonomic neuropathy, hyperadrenergic state, hypovolemia, venous pooling, joint hypermobility, deconditioning). Neurally mediated syncope occurs despite intact autonomic reflexes. Management of orthostatic intolerance aims to increase functional capacity, including standing time, performance of daily activities, and exercise tolerance. Nonpharmacologic strategies (fluid and salt loading, physical countermaneuvers, compression garments, exercise training) are fundamental for patients with POTS, occasionally complemented by medications to raise blood pressure or slow heart rate. Neurally mediated syncope is best managed by recognition and avoidance of triggers. Significant negative effects on quality of life occur in patients with POTS and in patients with recurrent neurally mediated syncope, which can be mitigated through targeted evaluation and thoughtful management.

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.

Gulf War Illness affects 25-32% of veterans from the 1990-91 Persian Gulf War. Post-exertional malaise with cognitive dysfunction, pain and fatigue following physical and/or mental effort is a defining feature of Gulf War Illness. We modelled post-exertional malaise by assessing changes in functional magnetic resonance imaging at 3T during an N-Back working memory task performed prior to a submaximal bicycle stress test and after an identical stress test 24 h later. Serial trends in postural changes in heart rate between supine and standing defined three subgroups of veterans with Gulf War Illness: Postural Orthostatic Tachycardia Syndrome (GWI-POTS, 15%,  = 11), Stress Test Associated Reversible Tachycardia (GWI-START, 31%,  = 23) and Stress Test Originated Phantom Perception (GWI-STOPP, no postural tachycardia, 54%,  = 46). Before exercise, there were no differences in blood oxygenation level-dependent activity during the N-Back task between control ( = 31), GWI-START, GWI-STOPP and GWI-POTS subgroups. Exercise had no effects on blood oxygenation level-dependent activation in controls. GWI-START had post-exertional deactivation of cerebellar dentate nucleus and vermis regions associated with working memory. GWI-STOPP had significant activation of the anterior supplementary motor area that may be a component of the anterior salience network. There was a trend for deactivation of the vermis in GWI-POTS after exercise. These patterns of cognitive dysfunction were apparent in Gulf War Illness only after the exercise stressor. Mechanisms linking the autonomic dysfunction of Stress Test Associated Reversible Tachycardia and Postural Orthostatic Tachycardia Syndrome to cerebellar activation, and Stress Test Originated Phantom Perception to cortical sensorimotor alterations, remain unclear but may open new opportunities for understanding, diagnosing and treating Gulf War Illness.

The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI. 429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we administered a verbal questionnaire to ascertain for 15 OI symptoms. End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P < .0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI symptoms with the degree of CBF reduction at mid-tilt (P < .0005). During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities. This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.

An unusual case of infectious mononucleosis complicated by both peritonsillar abscess and postural orthostatic tachycardia syndrome is reported. The patient was diagnosed with Epstein-Barr virus infection early in the disease course by her primary care doctor. She subsequently developed a peritonsillar abscess requiring hospitalisation. Recovery was complicated by the development of postural orthostatic tachycardia syndrome. However, resolution was achieved over the course of approximately 1 year, via conservative measures including graded exercise therapy, without resorting to pharmacotherapy.

Myalgic Encephalomyelitis (ME) is a complex, chronic, disabling, multi-system disease with no FDA-approved treatments. ME greatly impacts quality of life (QoL) with studies showing that people with ME often have worse quality of life than people with sickle cell anemia and cystic fibrosis, among other chronic diseases. People with ME frequently have comorbidities, which, if treated, could improve quality of life. However, the pervasive impact of ME makes treatment of comorbidities difficult. When trying to treat comorbidities it is therefore important for rehabilitation specialists to understand the impact of ME on day-to-day life in order to avoid treatment-related harms or exacerbation of ME symptoms. This article details the lived experience of one family in which both siblings have ME and comorbidities.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disease that predominantly affects children and adolescents. There is a great difference between children and adults in the diagnosis and treatment of POTS patients. POTS in children and adolescents is marked by chronic symptoms of orthostatic intolerance with a heart rate (HR) rise of ≥40 bpm, or heart rate exceeding 130 bpm for 6-12-years-old children and exceeding 125 bpm for those 13-18 years old without orthostatic hypotension, which is different from adult patients. The three major clinical forms of POTS include hypovolemic POTS, neuropathic POTS, and hyperadrenergic POTS; these are distinguished by their major mechanisms. The different subtypes of POTS in children and adolescents each have their own clinical characteristics and biomarkers. Based on these, we propose individualized treatment strategies. Individualized management strategies based on different subtypes of POTS would largely improve the curative effects of drugs for children with POTS. However, a further clinical investigation is still required to better understand the pathophysiology and treatment options.

Orthostatic intolerance (OI) is common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Cognitive dysfunction has been demonstrated during head-up tilt testing (HUT) in those with ME/CFS: worse scores on cognitive tests occur with increasing tilt angles and increasing complexity of the cognitive challenge. The aim of our study was to determine whether cognitive impairment persists after completion of HUT. Eligible participants were consecutive individuals satisfying criteria for ME/CFS who underwent HUT because of OI. The 2- and 3-back tests were performed before the start of HUT and within 5 min after completion of HUT. We measured the percentage of correct responses and raw reaction times before and after HUT for both the 2- and 3-back tests. We studied 128 ME/CFS patients who underwent HUT and had a complete set of N-back data before and after HUT. Compared to pre-tilt responses, the percentage of correct responses on the 2-back test decreased post-HUT from 77(18) to 62(21) and of the 3-back test from 57(17) to 41(17) (both < 0.0001). The raw reaction time of the 2-back test increased post-HUT from 783(190) to 941(234) m/s and of the 3-back test from 950(170) to 1102(176) (both < 0.0001). There was no difference in the N-back test data for subgroups dichotomized based on disease severity, the presence of co-morbid fibromyalgia, or the presence of postural orthostatic tachycardia syndrome. As measured by the N-back test, working memory remains impaired in adults with ME/CFS following a 30-min head-up tilt test.

Cardiovascular autonomic dysfunction in cancer survivors is poorly understood. To better characterize the clinical characteristics and types of autonomic dysfunction in this population. A retrospective analysis of cancer survivors within an academic cardio-oncology program referred for suspected autonomic dysfunction was performed. Autonomic reflex testing of adrenergic, cardiovagal, and sudomotor function was done. Autonomic impairment was graded on severity based on the Composite Autonomic Severity Score system. Patients with pre-existing autonomic dysfunction prior to their cancer diagnosis were excluded. Of approximately 282 total patients in the UCLA Cardio-Oncology program, 24 were referred for suspected autonomic dysfunction and met the inclusion criteria. 22 had autonomic impairment on autonomic reflex testing. Eight patients were female, and the mean age at time of autonomic testing was 51.3 years. The average duration from cancer diagnosis to autonomic testing was 10.3 years. The reasons for referral included dizziness, tachycardia, palpitations, and syncope. The majority of patients (75%) had hematologic disorders. The most common chemotherapies administered were vinca alkaloids (54.2%), alkylating agents (66.7%), and anthracyclines (54.2%). Most patients received radiation to the thorax (66.7%) and neck (53.3%). Eleven patients had mild autonomic impairment, 7 had moderate, and 4 had severe autonomic impairment. Dysfunction was commonly present in the sympathetic and parasympathetic branches, but most pronounced in the sympathetic system. The majority of patients were diagnosed with orthostatic hypotension (50%), inappropriate sinus tachycardia (20.8%), and postural orthostatic tachycardia syndrome (12.5%) and had subjective improvement with treatment. Cardiovascular autonomic dysfunction occurs in cancer survivors, and commonly affects both the sympathetic and parasympathetic systems. Symptom recognition in patients should prompt autonomic testing and treatment where appropriate.

Vasovagal syncope, postural orthostatic tachycardia syndrome, and inappropriate sinus tachycardia comprise a heterogenous group of common autonomic disorders that are associated with significant symptoms that impair quality of life. Clinical management of these disorders should prioritize conservative non-pharmacological therapies and consider incorporating pharmacological agents for recurrences. The selection and titration of medications may be complicated by the occurrence of potentially overlapping pathophysiological variants, differences in specific clinical presentations, and commonly associated comorbidities. However, with appropriate long-term management and specialist input, most patients note both symptomatic improvement and functional restoration over time.

The cardiovascular branch of autonomic nervous system (ANS) is responsible for the regulation of heart rate, blood pressure, and maintaining homeostasis during physiological stress such as exercise and standing upright. ANS constantly controls the rate and force of heart contractions and the vascular tone with the aim to maintain the sufficient tissue perfusion with oxygenated blood and secure venous return to the heart. Dysautonomias, result of ANS malfunction, are often found in patients with cardiovascular symptoms. Apart from the most prevalent one, arterial hypertension, the cardiovascular dysautonomic continuum encompasses other important although less known conditions: postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension and reflex syncope. Moreover, heart diseases may evoke autonomic imbalance by themselves; cardiac pump failure is usually associated with sympathetic hyperactivity, neuroendocrine vasopressor activation, higher heart rate, reduced heart rate variability and baroreflex hyposensitivity, all of which are predictors of adverse outcomes. Cardiologists and electrophysiologist frequently see patients for the evaluation and management of unexplained syncope, orthostatic intolerance, heart rhythm abnormalities and symptoms of palpitations. Recognizing the presence of cardiac dysautonomia is an important skill which is necessary for the appropriate evaluation and treatment of these patients. Clinical presentations may overlap, and the importance of a thorough history cannot be over-emphasized. In this review we will present a cases of a patients with cardiac dysautonomia which is illustrative of a typical patient experience, followed by a review of the autonomic nervous system and discussion of prevalence, clinical presentation, and pathophysiology of common cardiac dysautonomias.

Patients with postural orthostatic tachycardia syndrome (POTS) present to outpatient dysautonomia clinics endorsing a wide range of symptoms. Dry eyes and mouth, or sicca complex are frequently reported. This retrospective study investigates the incidence and quantifies the severity of dry eye syndrome (DES) in patients with POTS. This retrospective study compiles survey results, and dry eye clinical data from twenty-three POTS patients (22 females, average age 34.9 and st dev 14.0 years) surveyed during their initial or follow-up appointments. Patient's medication lists were documented to account for anticholinergics, antihistamines, and anticholinesterase use. Patients endorsing dry eye symptoms were tested with Schirmer's test strips to identify clinically dry eyes and stratified for severity. Sixty-five percent of patients endorsed dry eye symptoms (15/23). Seventy-four percent of patients endorsed dry mouth symptoms (17/23). Among patients endorsing dry eyes, 81% of eyes had decreased tear production with Schirmer's strip wetting less than 10 mm/5 min (13/16). DES is an additional and significant disease burden for the POTS patient population. Dry eye and exocrine gland function should be evaluated as part of the dysautonomia work up with referral to ophthalmology as appropriate. Patients with clinically dry eyes who report additional autonomic dysfunction should be further evaluated for widespread autonomic dysfunction.

Postural orthostatic tachycardia syndrome (POTS) is a chronic, multifactorial syndrome with complex symptoms of orthostatic intolerance. Breathlessness is a prevalent symptom, however little is known about the aetiology. Anecdotal evidence suggests that breathless POTS patients commonly demonstrate dysfunctional breathing/hyperventilation syndrome (DB/HVS). There are, however, no published data regarding DB/HVS in POTS, and whether physiotherapy/breathing retraining may improve patients' breathing pattern and symptoms. The aim of this study was to explore the potential impact of a physiotherapy intervention involving education and breathing control on DB/HVS in POTS. A retrospective observational cohort study of all patients with POTS referred to respiratory physiotherapy for treatment of DB/HVS over a 20-month period was undertaken. 100 patients (99 female, mean (standard deviation) age 31 (12) years) with a clinical diagnosis of DB/HV were referred, of which data was available for 66 patients pre - post intervention. Significant improvements in Nijmegen score, respiratory rate and breath hold time (seconds) were observed following treatment. These data provide a testable hypothesis that breathing retraining may provide breathless POTS patients with some symptomatic relief, thus improving their health-related quality of life. The intervention can be easily protocolised to ensure treatment fidelity. Our preliminary findings provide a platform for a subsequent randomised controlled trial of breathing retraining in POTS.

Limited data are available regarding the demographics, disease associations, and long-term prognosis of patients with inappropriate sinus tachycardia (IST). To establish epidemiologic data for patients with IST, including symptom onset, comorbid disease, and long-term outcomes. We retrospectively reviewed all patients with an IST diagnosis at the Mayo Clinic (Rochester, MN) during a 20-year period (1998-2018). We extracted demographic data and clinical outcomes compared to an age and gender-matched control group with atrioventricular nodal reentry tachycardia (AVNRT). Within the study period, a total of 305 patients with IST were identified (mean follow-up 3.5 years) with 92.1% female and mean age 33.2 ± 11.2 years. The most frequently identified circumstances triggering the condition included pregnancy (7.9%) and infectious illness (5.9%) while the most common comorbid conditions were depression (25.6%) and anxiety (24.6%). At diagnosis, the mean left ventricular ejection fraction (LVEF) was 62.3 ± 6.2%, with 77 patients having follow-up echocardiographic data. No significant difference in LVEF was seen after a mean 4.9 ± 4.3-year follow-up (baseline LVEF 59.8 ± 10.7% vs subsequent 61.4 ± 8.1%; P = .2971). Two deaths occurred within the study period, with one related to myocardial infarction and the other noncardiac; compared to an age and gender-matched AVNRT control group there was no excess mortality during the follow-up period. In our study cohort, IST predominately affects young females with structurally normal hearts and modest coexistent psychiatric disease. In most cases of IST, a major event occurring just before or at the time of diagnosis could not be identified, although nearly 8% of patients first noted symptoms during or shortly after pregnancy. In our cohort, there was no evidence of cardiomyopathy or mortality related to IST.

Delay differential equations are widely used in mathematical modeling to describe physical and biological systems, often inducing oscillatory behavior. In physiological systems, this instability may signify (i) an attempt to return to homeostasis or (ii) system dysfunction. In this study, we analyze a nonlinear, nonautonomous, nonhomogeneous open-loop neurological control model describing the autonomic nervous system response to the Valsalva maneuver (VM). We reduce this model from 5 to 2 states (predicting sympathetic tone and heart rate) and categorize the stability properties of the reduced model using a two-parameter bifurcation analysis of the sympathetic delay (D) and time-scale (τ). Stability regions in the Dτ-plane for this nonhomogeneous system and its homogeneous analog are classified numerically and analytically, identifying transcritical and Hopf bifurcations. Results show that the Hopf bifurcation remains for both the homogeneous and nonhomogeneous systems, while the nonhomogeneous system stabilizes the transition at the transcritical bifurcation. This analysis was compared with results from blood pressure and heart rate data from three subjects performing the VM: a control subject exhibiting sink behavior, a control subject exhibiting stable focus behavior, and a patient with postural orthostatic tachycardia syndrome (POTS) also exhibiting stable focus behavior. Results suggest that instability caused from overactive sympathetic signaling may result in autonomic dysfunction.

Human papillomavirus (HPV) vaccination has been anecdotally connected to development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome. To critically evaluate a potential connection between HPV vaccination and above noted conditions. We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders. At this time the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, POTS or other forms of dysautonomia. Certain conditions are prevalent in the same patient populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is insufficient proof of causality.

Although diagnostic criteria have been developed characterizing postural orthostatic tachycardia syndrome (POTS), no single set of criteria is universally accepted. Furthermore, there are gaps in the present criteria used to identify individuals who have this condition. The reproducibility of the physiological findings, the relationship of symptoms to physiological findings, the presence of symptoms alone without any physiological findings and the response to various interventions confuse rather than clarify this condition. As many disease entities can be confused with POTS, it becomes critical to identify what this syndrome is. What appears to be POTS may be an underlying condition that requires specific therapy. POTS is not simply orthostatic intolerance and symptoms or intermittent orthostatic tachycardia but the syndrome needs to be characterized over time and with reproducibility. Here we address critical issues regarding the pathophysiology and diagnosis of POTS in an attempt to arrive at a rational approach to categorize the syndrome with the hope that it may help both better identify individuals and better understand approaches to therapy.

Postural tachycardia syndrome (POTS) is a suspected dysautonomia with symptoms of orthostatic intolerance and abnormally increased heart rate while standing. We aimed to study cardiac autonomic nervous system functioning in head-up tilt (HUT) in adolescents with POTS to find out if parasympathetic tone is attenuated in the upright position. We compared characteristics of a group of 25 (females 14/25; 56%) adolescents with POTS and 12 (females 4/12; 34%) without POTS aged 9-17 years. We compared heart rate variability with high- and low-frequency oscillations, and their temporal changes in HUT. The high-frequency oscillations, i.e., HF, attenuated in both groups during HUT ( < 0.05), but the attenuation was bigger in POTS ( = 0.04). In the beginning of HUT, low-frequency oscillations, i.e., LF, increased more in POTS ( = 0.01), but in the end of HUT, an attenuation in LF was seen in the POTS group ( < 0.05), but not in the subjects without POTS. There were no associations of previous infections or vaccinations with POTS. Subjects with POTS were sleepier and their overall quality of life was very low. The results imply to an impaired autonomic regulation while standing in POTS, presenting as a lower HF and higher LF in the beginning of HUT and an attenuated LF in the prolonged standing position.

Postural tachycardia syndrome (POTS), characterized by chronic (≥6 months) orthostatic intolerance symptoms with a sustained and excessive heart rate increase while standing without postural hypotension, is common in children and adolescents. Despite the unclear pathogenesis of POTS, the present opinion is that POTS is a heterogeneous and multifactorial disorder that includes altered central blood volume, abnormal autonomic reflexes, "hyperadrenergic" status, damaged skeletal muscle pump activity, abnormal local vascular tension and vasoactive factor release, mast cell activation, iron insufficiency, and autoimmune dysfunction. A number of pediatric POTS patients are affected by more than one of these pathophysiological mechanisms. Therefore, individualized treatment strategies are initiated in the management of POTS, including basal non-pharmacological approaches (e.g., health education, the avoidance of triggers, exercise, or supplementation with water and salt) and special pharmacological therapies (e.g., oral rehydration salts, midodrine hydrochloride, and metoprolol). As such, the recent progress in the pathogenesis, management strategies, and therapeutic response predictors of pediatric POTS are reviewed here.

Neurally mediated syncope (NMS) is the most common underlying disease of pediatric syncope, which generally includes vasovagal syncope (VVS), postural tachycardia syndrome (POTS), and situational syncope. Allergic diseases involving the respiratory system, digestive system, skin, and other systems are prevalent in children. In recent years, increasing attention has been paid to children with the comorbidity of NMS and allergic diseases. This article reviews the featured clinical manifestations and pathogenesis of the comorbidity according to the progress of related studies. Clinical studies have shown that the comorbidity rate of pediatric VVS and/or POTS with allergic diseases amounts to ~30-40%, referring to the whole population of children with VVS and/or POTS. Additionally, children with the comorbidity present some relatively special clinical characteristics. A series of mechanisms or regulatory factors relating to allergies, such as the imbalance of vasoactive elements, dysfunction of the autonomic nervous system (ANS), and autoimmunity may play a role in the development of the comorbidity. Moreover, 90% of children with cough syncope, a type of situational syncope, have a history of asthma, indicating a potential relationship between asthma and NMS. Further studies exploring the clinical characteristics and pathogenesis of the comorbidity are still needed to aid in the diagnosis and treatment of children with NMS.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic nervous system disorder causing an abnormal cardiovascular response to upright posture. It affects around 0.2% of the population, most commonly women aged 13 to 50 years. POTS can be debilitating; prolonged episodes of pre-syncope and fatigue can severely affect activities of daily living and health-related quality of life (HRQoL). Medical treatment is limited and not supported by randomised controlled trial (RCT) evidence. Lifestyle interventions are first-line treatment, including increased fluid and salt intake, compression tights and isometric counter-pressure manoeuvres to prevent fainting. Observational studies and small RCTs suggest exercise training may improve symptoms and HRQoL in POTS, but evidence quality is low. Sixty-two people (aged 18-40 years) with a confirmed diagnosis of POTS will be invited to enrol on a feasibility RCT with embedded qualitative study. The primary outcome will be feasibility; process-related measures will include the number of people eligible, recruited, randomised and withdrawn, along with indicators of exercise programme adherence and acceptability. Secondary physiological, clinical and health-related outcomes including sub-maximal recumbent bike exercise test, active stand test and HRQoL will be measured at 4 and 7 months post-randomisation by researchers blinded to treatment allocation. The PostUraL tachycardia Syndrome Exercise (PULSE) intervention consists of (1) individual assessment; (2) 12-week, once to twice-weekly, supervised out-patient exercise training; (3) behavioural and motivational support; and (4) guided lifestyle physical activity. The control intervention will be best-practice usual care with a single 30-min, one-to-one practitioner appointment, and general advice on safe and effective physical activity. For the embedded qualitative study, participants ( = 10 intervention, = 10 control) will be interviewed at baseline and 4 months post-randomisation to assess acceptability and the feasibility of progressing to a definitive trial. There is very little high-quality research investigating exercise rehabilitation for people with POTS. The PULSE study will be the first randomised trial to assess the feasibility of conducting a definitive multicentre RCT testing supervised exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with POTS. ISRCTN45323485 registered on 7 April 2020.

A number of published literature has reported that, physiologically, heart rate variability (HRV) in patients with postural orthostatic tachycardia syndrome (POTS) to be greatly confounded by age, sex, race, physical fitness, and circadian rhythm. The purpose of this study was to compare between POTS patients versus healthy participants, in terms of heart rate (HR) and HRV after Head-Up tilt test (HUTT), by systematic review and meta-analysis of available published literature. MEDLINE (using PubMed interphase), EMBASE and SCOPUS were systematically searched for observational studies comparing POTS patients versus healthy patients, in terms of HR and HRV. HRV was grouped into Time and frequency domain outcome measurements. The time domain was measured as mean RR- interval and mean the square root of the mean of squares of successive R-R waves (rMSSD) in milliseconds. The frequency domain was measured as mean values of Low frequency power (LF), High frequency power (HF), LF/HF-ratio, LF-normalized units (LF(n.u)) and HF-normalized units (HF(n.u)). Demographic data, comorbidities, and mean values of HR, RR- interval, rMSSD, LF, HF, LF/HF-ratio, LF-(n.u) and H.F-n.u were extracted from each group and compared, by their mean differences as an overall outcome measure. Computer software, RevMan 5.3 was utilized, at a 95% significance level. Twenty (20) eligible studies were found to report 717 POTS and 641 healthy participants. POTS group had a higher mean HR (p < 0.05), lower mean RR-Interval (p < 0.05), lower rMSSD (p < 0.05) than healthy participants. Furthermore, POTS group had lower mean HF(p > 0.05), lower mean LF(p > 0.05), and lower mean HF(n.u) (p > 0.05), higher LF/HF-Ratio (p > 0.05) and higher LF(n.u) (p > 0.05) as compared to healthy participants. POTS patients have a higher HR than healthy patients after HUTT and lower HRV in terms of time domain measure but not in terms of frequency domain measure. HR and time domain analyses of HRV are more reliable than frequency domain analysis in differentiating POTS patients from the healthy participants. We call upon sensitivity and specificity studies.

Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. In prior studies, measurement of AAb activity was inferred from costly, low-throughput, and laborious physiological assays. In the present study, we developed and validated an alternative cell-based bioassay for measuring AAb activity in serum by means of pre-treatment with monoamine oxidase (MAO). A total of 37 POTS patients and 61 sex-matched healthy control participants were included. Serum was pre-treated with MAO to remove endogenous catecholamines that could falsely inflate AR activation by AAb. A receptor-transfected cell-based bioassay was used to detect presence of α1AR-AAb and β1AR-AAb in serum. MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 ​± ​0.7 vs. 5.5 ​± ​0.9;  ​= ​0.044) and in controls (4.1 ​± ​0.5 vs. 3.9 ​± ​0.6;  ​= ​0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 ​± ​1.2 vs. 5.3 ​± ​1.0;  ​< ​0.001) and β1AR-AAb (5.7 ​± ​1.8 vs. 4.1 ​± ​0.9;  ​< ​0.001). Compared to controls, more POTS patients were positive for α1AR-AAb activity (22% vs 4%; P ​= ​0.007) and β1AR-AAb activity (52% vs. 2%; P ​< ​0.001). The co-presence of norepinephrine in serum samples can artifactually elevate α1AR and β1AR activity, which can be avoided by serum pre-treatment with MAO. Using this novel bioassay, we show that POTS patients have increased α1AR-AAb and β1AR-AAb activity compared to healthy controls in the largest POTS cohort reported to-date.

To study the outcomes of a series of consecutive tilt table tests combined with video-EEG (TTVE) at a single center, and assess their cost-effectiveness compared with other neurophysiological tests. We retrospectively reviewed medical records of patients who underwent TTVE studies between March 1, 2013 to April 1, 2018. Detailed clinical history, including patient demographics, reasons for referral, anti-seizure medications, and neurophysiological studies obtained prior to the TTVE studies were extracted from chart reviews. The fee for each neurophysiological test was identified from the Centers for Medicare & Medicaid Services. Fifty-two patients underwent TTVE studies. Thirteen patients (25%) were diagnosed with vasovagal syncope, two (3.8%) were diagnosed with postural orthostatic tachycardia syndrome, and three (5.8%) had psychogenic non-epileptic events during the test. Four out of 12 patients stopped anti-seizure medication(s) after the TTVE. Prior to referral for TTVE, an average of $3,748 per person was spent on neurophysiological tests, which were inconclusive. The average fee for one TTVE test was $535.32, and the fee per test affecting diagnosis or management (defined as the cost divided by the yield of the test) was $1,547. The TTVE test is cost-effective in evaluating refractory episodes of loss of consciousness, atypical of epileptic seizures. In addition to diagnosing syncope, TTVE can be valuable in identifying psychogenic events.

To evaluate whether equal volumes of oral rehydration solution (ORS) or intravenous (IV) saline provide similar improvements in cardiovascular status during controlled orthostatic challenge when administered to subjects with postural tachycardia syndrome (POTS) with orthostatic intolerance. We studied the neurovascular response to fluid loading during orthostatic stress using lower body negative pressure (LBNP) in 10 subjects with POTS with orthostatic intolerance and 15 controls, and on subsequent days before and 1 hour after IV saline infusion or ingestion of ORS. Subjects with POTS exhibited reduced tolerance to LBNP (P < .0001) compared with controls (Orthostatic Index of 35 715 ± 3469 vs 93 980 ± 7977, respectively). In POTS, following ORS but not saline infusion, cerebral blood flow velocity (CBF) was significantly higher than that with no treatment, at -45 mm Hg (P < .0005). Although fluid loading did not confer any advantage in controls, subjects with POTS experienced a significant improvement in orthostatic tolerance following both saline infusion (100 ± 9.7 vs 134.5 ± 17.4; P < .05) and ORS (100 ± 9.7 vs 155.6 ± 15.7; P < .001) when evaluated by normalized orthostatic index (P < .001, compared with untreated baseline). Maintenance of CBF may have resulted in the improved short-term orthostatic tolerance exhibited by the subjects with POTS following ORS administration. ORS is a convenient, safe, and effective therapy for short-term relief of orthostatic intolerance.