Postural orthostatic tachycardia syndrome (POTS) is a chronic condition associated with a high symptom burden and decreased quality of life (QOL). Exercise is currently considered to be a first line non-pharmacological treatment for POTS. The purpose of this systematic review was to evaluate the impact of exercise on cardiovascular and patient-centered outcomes in patients with POTS. To evaluate whether exercise benefits patients with POTS by synthesizing data from published clinical studies. Electronic databases, including Medline, Embase, CINAHL Complete, Cochrane CENTRAL, and others were searched and results were exported on May 2, 2023. Study inclusion: those that utilized an exercise program as an intervention for POTS and were conducted as experimental or quasi-experimental design. Exclusions: Non-English language papers and opinion-based/theoretical/non-empirical studies/case reports. Data extraction was based on Cochrane Handbook guidance and summarized according to Synthesis Without Meta-analysis (SWiM) guidelines; methodological quality and risk of bias was evaluated using the JBI Critical Appraisal tools. Standardized effects were calculated and summarized based on the direction of effect. Seven studies included in the final review are described in the data summary and synthesis. Improvements in heart rate were reported across all studies reviewed, while stroke volume and QOL improvements were also found. Notably, not all studies reported on the latter two outcomes. Methodological variability across studies precluded meta-analysis, and risk of bias was considered moderate-high in all but a single study. While currently available evidence supports exercise as beneficial to QOL and cardiovascular features of POTS, we identified a major need for additional studies assessing the effect of exercise on symptom burden and daily function, including studies that consider patients with specific comorbidities that impact exercise tolerability and/or dosing.

To explore the correlation between orthostatic intolerance in children and levels of the ACE2-Ang(1-7)-Mas axis and vitamin D. Blood samples were collected from 84 children with orthostatic intolerance and 307 healthy controls. After matching for age and sex, 84 children from each group were studied. The orthostatic intolerance group was divided into vasovagal syncope ( = 51) and postural orthostatic tachycardia syndrome ( = 33). Fasting blood samples were analyzed for 25(OH)D, ACE2, Ang(1-7), and hydroxylases using ELISA. (1) The orthostatic intolerance group had significantly lower levels of ACE2, Ang(1-7), 25(OH)D, and hydroxylases compared to controls ( < 0.05). (2) No sex differences in biomarker levels were found in the orthostatic intolerance group ( > 0.05), but boys in the control group had higher 25(OH)D levels ( < 0.001). (3) No significant differences between the two intolerance subgroups ( > 0.05). (4) Logistic regression showed lower levels of 25(OH)D, 25-hydroxylase, and Ang(1-7) correlated with higher orthostatic intolerance incidence. (5) Ang(1-7) levels of 19.39 ng/ml provided 86.9% sensitivity and 61.9% specificity for diagnosis. Reduced levels of Ang(1-7)/ACE2, 25(OH)D, and 25-hydroxylase are linked to orthostatic intolerance in children, highlighting vitamin D deficiency's role and suggesting Ang(1-7) and ACE2 as potential biomarkers. Sex does not significantly affect these biomarker levels.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an increased heart rate upon standing, resulting from abnormal autonomic responses that trigger symptoms when transitioning to an upright position. This syndrome predominantly manifests in late adolescence and early adulthood, with a higher prevalence observed in women. It is commonly triggered by viral infections, pregnancy, surgical procedures, or significant psychological stress. The condition presents with a wide range of symptoms, and the precise etiology of which remains unidentified. A 17-year-old woman with recurrent syncope was admitted to the hospital multiple times. Symptoms resolved rapidly following the initiation of paroxetine, a selective serotonin reuptake inhibitor (SSRI). Preliminary analysis indicated a potential shared pathophysiological basis between POTS and anxiety disorders, with norepinephrine transporter proteins emerging as a significant therapeutic target for both conditions.

Exercise training is recommended for PoTS; however, very few studies have examined the effectiveness of exercise training in young adolescents with PoTS. We evaluated the effects of ergometer endurance exercise on the circulatory dynamics of children with PoTS using cardiopulmonary exercise (CPX) testing, standing tests, and cardiac output monitoring. Overall, 28 participants with PoTS (19 males) aged 12-15 years were admitted to the Department of Pediatrics, Kansai Medical University General Medical Center, for 1 month between August 2020 and November 2023. Of the participants, 17 were assigned to the exercise group (13 boys) and 11 were assigned to the control group (6 boys). All participants underwent the standing test and CPX testing upon admission. The exercise group performed ergometer exercise for 30 min once per day, five times per week for 4 weeks. After 4 weeks, both groups completed the standing and CPX tests again. During the standing test, the patients underwent non-invasive hemodynamic monitoring using the AESCULON Mini®. There were no significant differences between the two groups in demographic characteristics at admission (before the start of exercise training). Stroke volume, cardiac output, cardiac index, and thoracic fluid content increased after exercise training in the exercise group [pre- vs. post-exercise: cardiac output (ml) 61.7 vs. 73.1 ( = 0.009); cardiac output (L/min): 6.6 vs. 7.7 ( = 0.001); cardiac index (L/min/m): 4.3 vs. 5.0 ( = 0.029); thoracic fluid content: 28.7 vs. 33.8 ( = 0.001)]. Exercise duration and maximal oxygen uptake (VO) increased after exercise training in the exercise group on CPX testing [pre- vs. post-exercise: load time (min): 1.8 vs. 9.6 ( = 0.002), peak VO (ml/min/kg): 30.3 vs. 33.2 ( = 0.005)]. The hemodynamic and CPX test results were unchanged in the control group. No significant changes were observed in orthostatic test results in either group. Endurance exercise training for 4 weeks increased cardiac output during orthostasis in children with PoTS and inhibited the downward migration of blood. We conclude that ergometer exercise training for 4 weeks in young adolescents with PoTS may improve circulatory dynamics during orthostasis.

Significant clinical similarities have been observed between the recently described "Long-Haul" COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspnea, "brain-fog," and fatigue. Ivabradine is a selective sinoatrial node blocker FDA-approved for management of tachycardia associated with stable angina and heart failure not fully managed by beta blockers. In our study we aim to identify risk factors underlying LHC, as well as the effectiveness of ivabradine in controlling heart rate dysregulations and POTS/IST related symptoms. A detailed prospective phenotypic evaluation combined with multi-omic analysis of 200 LHC volunteers will be conducted to identify risk factors for autonomic dysfunction. A comparator group of 50 volunteers with documented COVID-19 but without LHC will be enrolled to better understand the risk factors for LHC and autonomic dysfunction. Those in the cohort who meet diagnostic criteria for POTS or IST will be included in a nested prospective, randomized, placebo-controlled trial to assess the impact of ivabradine on symptoms and heart rate, assessed non-invasively based on physiologic response and ambulatory electrocardiogram. Additionally, studies on catecholamine production, mast cell and basophil degranulation, inflammatory biomarkers, and indicators of metabolic dysfunction will be measured to potentially provide molecular classification and mechanistic insights. Optimal therapies for dysautonomia, particularly associated with LHC, have yet to be defined. In the present study, ivabradine, one of numerous proposed interventions, will be systematically evaluated for therapeutic potential in LHC-associated POTS and IST. Additionally, this study will further refine the characteristics of the LHC-associated POTS/IST phenotype, genotype and transcriptional profile, including immunologic and multi-omic analysis of persistent immune activation and dysregulation. The study will also explore and identify potential endotheliopathy and abnormalities of the clotting cascade. https://clinicaltrials.gov/, identifier NCT05481177.

Postural orthostatic tachycardia syndrome (POTS) affects up to 3 million people in the United States. Although 78%-83% of POTS patients are female, gynecologic comorbidity has not been well-studied. We created an online questionnaire to assess outcomes in female patients with POTS formerly followed at a single-center pediatric POTS program. Cross-sectional study. Single-center pediatric POTS program. All female patients ≤ 18 years at diagnosis. We developed and distributed The Long-Term POTS Outcomes Survey with questions about diagnosis, therapy, education, employment, social impact, quality of life (QoL), and gynecologic symptoms and management. Gynecologic symptoms and QoL. Regular menstrual cycles were seen in 81/167 participants (49.1%). POTS symptoms worsened prior to and during menses in 118/167 subjects (72.4%); hormonal contraceptive therapy helped to control symptoms in 52/110 subjects (50%). Menorrhagia, polycystic ovary syndrome, and endometriosis were not reported in higher numbers compared to the general population. Menstrual flow disorders are not more prevalent in younger females with POTS. Symptoms often worsen perimenstrually, and hormone therapy can help to reduce symptom severity. Further research is needed to better define optimal hormone therapy in suppressing perimenstrual symptoms.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease characterized by exertional intolerance and fatigue which is often accompanied by muscle weakness and fatiguability. A study showed efficacy of the acetylcholinesterase inhibitor pyridostigmine on cardiac output in ME/CFS patients. Pyridostigmine is currently used off-label in ME/CFS and postural orthostatic tachycardia syndrome. We evaluated the effect of pyridostigmine on hand grip strength in 20 patients with post-infectious ME/CFS. Hand grip strength testing was performed ten times using an electric dynamometer and was repeated after 1 h. In a second test, 30 mg of pyridostigmine was given immediately after the first measurement. Orthostatic function was assessed using a passive standing test. Neurological examination and autoantibody testing were performed to rule out a diagnosis of myasthenia gravis. All patients had reduced maximum hand grip strength with a median of 16.45 kg (IQR: 11.45 kg-22.8 kg). Hand grip strength was diminished by a median of 4.65 kg after 1 h. In contrast, 1 h after pyridostigmine administration, patients showed an improvement in maximum hand grip strength with a median increase of 2.6 kg. The maximum hand grip strength after exertion was about 1.5-fold higher with then without pyridostigmine ( 0.01). The increase in heart rate from lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats per minute - 23 beats per minute) and 13 beats per minute (IQR: 9 beats per minute - 20 beats per minute) ( = 0.017) with pyridostigmine. None of the patients tested positive for myasthenia gravis specific autoantibodies. Pyridostigmine exerts an immediate effect on muscle strength and orthostatic function. This may be attributed to increased acetylcholine availability at neuromuscular junctions, and its augmentation of parasympathetic tone.

Postural orthostatic tachycardia syndrome (POTS), a type of dysautonomia, has been an enigma to many healthcare providers. As many as 80% of coronavirus disease 2019 (COVID-19) long-hauler patients meet the diagnostic criteria for POTS, highlighting awareness of this debilitating multisystem disorder. The etiology of POTS has not been entirely defined, but researchers have speculated that an immunological stressor such as a viral infection might be an initiating event. Prior to the pandemic, we reported that POTS patients have a bleeding diathesis with platelet dense granule storage pool deficiency (δ-SPD). This report presents a prospective case-control study ( = 252) involving four cohorts, comprising two groups of POTS patients and two groups of healthy controls, to evaluate abnormal bleeding and patient demographics. We compared POTS patients and controls that were naïve to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus with subjects that had been infected and subsequently developed POTS or who recovered healthy. Questionnaires were employed to assess bleeding tendencies and the severity of clinical symptoms commonly reported with POTS. We utilized electron microscopy to assess platelet dense granules and enzyme-linked immunosorbent assay (ELISA) to assess COVID-19 and Epstein-Barr viral titers. The most common bleeding symptom was easy bruising in POTS patients naïve to COVID-19 (79.7%) and POTS post-COVID-19 patients (90.5%). Both groups had δ-SPD with means of 2.52 ± 0.9 and 2.44 ± 0.9 DG/PL, respectively, in contrast to a mean of 4.33 ± 0.6 DG/PL for controls naïve to SARS-CoV-2 infection and 4.19 ± 1.0 DG/PL for controls recovered from the virus ( < 0.001). We found that the results between the two POTS groups have no statistically significant difference. Our results identify an additional comorbidity (δ-SPD) in COVID-19 "long haulers"/post-acute sequela of COVID-19 (PASC) patients, frequently seen in POTS, that could explain several disparate symptoms often a??ecting the severity of the condition.

Persistent postural-perceptual dizziness (PPPD) is characterized by one or more symptoms of dizziness, unsteadiness, or non-spinning vertigo, which persist on most days for at least 3 months. The most common symptom of PPPD worsens when standing or walking, often leading to confusion with other forms of orthostatic dizziness (OD). There are some main differential diagnosis as follows: hemodynamic OD, postural orthostatic tachycardia syndrome, vestibular syncope, BPPV, bilateral vestibulopathy, primary orthostatic tremor, sensory neuropathy, neurodegenerative disorders, cerebral small vessel disease associated with gait disorders, dizziness due to cardiac problems, orthostatic cerebral hypoperfusion syndrome, intracranial hypotension, and the possible mechanisms by which these diseases are associated with OD are briefly elaborated. However, the mechanism underlying OD in PPPD patients remains unclear. There are some impact factors of OD with PPPD, including sex and age, anxiety state and neurotic personality, comorbid vestibular disorders. There are some underlying mechanisms of OD with PPPD, such as altered activity and connectivity of cerebral cortical networks, vestibular-autonomic dysfunction and sensory-perceptual dysfunction, hemodynamic changes, changes in postural control, otolith dysfunction, visual and somatosensory dependence, neurotransmitter abnormalities. For patients with established PPPD, it is important to distinguish the etiologies of OD from other relevant diseases, enabling early intervention and preventing adverse effects on workability, and evaluate responses to therapies to reduce diagnostic errors and missed diagnoses.

Orthostatic intolerance syndromes such as Orthostatic Hypotension (OH) and Postural Orthostatic Tachycardia Syndrome (PoTS) are common symptoms seen in post-infection conditions and other neurological conditions with autonomic dysfunction. The 10-min Lean Test (LT) is an objective clinical test used to assess these symptoms and direct management. There is, however, no robust literature on normative data for this test, particularly from a younger population. The aim of this study was to produce a healthy control data set for LT, which can be used for comparison with the patient population with health conditions. Individuals recruited into the study had no history or symptoms of orthostatic intolerance; autonomic dysfunction; post-infection conditions (such as long COVID); or other neurological conditions with hemodynamic instability. Participants were primarily recruited from the general population in a metropolitan city. All participants underwent a standardized LT. Lying Blood Pressure (BP) and Heart Rate (HR) after 2 min of lying down supine was recorded, followed by BP and HR recordings at every minute of standing (leaning against a wall) up to 10 min, along with recording subject-reported symptoms at each time point. A complete dataset was available for 112 individuals (60.7% Female, 39.3% Male). The population was 61.6% Caucasian, 8.0% Asian, 3.6% Black/Caribbean, 9.8% Mixed, and 17.0% Other; the mean age was 35.3 ± 15.1, with a BMI of 24.8 ± 4.0; 30.6% of individuals had a background medical condition, but none of the exclusion criteria. During LT, upon standing, the average change of HR was an increase of 9.89 ± 8.15 bpm. The sustained HR increase (HR increase sustained at two consecutive readings) was an average of 6.23 ± 6.94 bpm. The predominant response with BP was an increase of systolic BP, with the average initial increase being 7.55 ± 10.88 mmHg. None of the participants met the diagnostic criteria for symptomatic OH or PoTS during LT. For the first time in the current literature, 10-min LT data from a relatively younger population without orthostatic intolerance have been gathered. This normative data will help interpret LT findings in younger patients with orthostatic Intolerance better and be useful in managing dysautonomia in specific conditions.

Complex chronic illnesses like Long Covid (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are marked by fluctuating symptoms, often exacerbated by physical, cognitive, or emotional exertion in a phenomenon known as post-exertional malaise (PEM). Home monitoring technologies offer potential benefits by enabling individuals to track symptoms and biometrics, aiding in disease self-management. However, the general effectiveness of such tools is still unknown. A random sample of users of the Visible mobile application (Visible Plus; requires both the armband and paid subscription), aged 18 or older and with self-identified complex chronic illnesses such as LC or ME/CFS, were invited to complete an online survey regarding the impact of the app on their chronic disease self-management. Descriptive statistics related to the responses were analyzed and reported. The survey was distributed to 2,636 people, with 1,301 participants responding (49.3% response rate). The average age was 46 years. 82% of respondents were female, 8% were male, 8% were non-binary, and 2% preferred not to say or preferred to self-describe. Participants self-identified as having ME/CFS only ( = 534, 42%), LC only ( = 396, 31%), ME/CFS and LC ( = 236, 18%), or another illness ( = 122, 10%). Of the  = 2,636 randomly selected subscribers, the mostly commonly listed "other illnesses" were Postural Orthostatic Tachycardia Syndrome (POTS, 6%), fibromyalgia (5.2%), Ehlers Danlos Syndrome (EDS; 1.7%) and Mast Cell Activation Syndrome (MCAS, 1.2%). Of those with at least 30 days of data, 77% reported seeing an improvements associated with app use, corresponding to 23% of all invited users, 85% (corresponding to 29% of all invited users) reported feeling somewhat (53%) or significantly (32%), and 94% (corresponding to 33% of all invited users) reported a better understanding of their energy budget. Home-monitoring based mobile applications are feasible and acceptable for a motivated subgroup of people with energy-limiting complex chronic illnesses, and are associated with self-reported benefits in energy management and participation in daily activities. The findings of this study should be interpreted as descriptive and hypothesis-generating and do not represent clinically significant effects, underscoring the need for randomized controlled trials to formally evaluate efficacy. Future studies should incorporate a comparison group to better differentiate intervention effects from improvements gained through lived experience.

Long COVID describes the persistence or recurrence of symptoms beyond the acute phase of SARS-CoV-2 infection and is increasingly recognized in children and adolescents. Despite its prevalence, understanding of symptom patterns and the influence of vaccination on disease trajectory in pediatric populations remains limited. We conducted a retrospective study of patients aged 0-21 years evaluated at the Long COVID Clinic at Children's Hospital Los Angeles between August 2021 and November 2023. Patients were included if they reported persistent or new symptoms ≥4 weeks after SARS-CoV-2 infection. A total of 123 patients were enrolled. The mean age was 13.1 years, and 51% were male. Symptom onset occurred a mean of 5 weeks after infection. At presentation, 56% of patients reported symptoms lasting 0-24 weeks, 28% for 25-52 weeks, and 16% for >52 weeks. Fatigue (93%) and headache (70%) were the most prevalent symptoms in both younger (<12 years) and older (>12 years) cohorts. Female patients more frequently reported brain fog, dizziness, palpitations, and postural orthostatic tachycardia syndrome. Overall symptom burden decreased significantly over time ( < 0.001). Vaccination status at baseline was not associated with difference in symptom duration on initial presentation ( = 0.4). However, among those vaccinated after developing long COVID, 41% reported subjective improvement in the following weeks. Pediatric long COVID is marked by prolonged, multisystem symptoms. Vaccination may offer symptomatic benefit for some patients, though larger prospective studies are necessary to better define its role.

Atraumatic splenic rupture is an extremely rare but serious complication of infectious mononucleosis. We present the case of an 18-year-old female who presented with atraumatic splenic rupture in the setting of infectious mononucleosis. Her past medical history was significant for postural orthostatic tachycardia syndrome, and she has a sister who was diagnosed with Ehlers-Danlos syndrome. Given her presentation and unique background, she was followed closely by surgery and hematology. The decision was made to pursue conservative management, and she was discharged home 4 days after admission with a 6-week physical activity restriction. This patient's medical and family history warranted unique clinical considerations and multidisciplinary collaboration throughout in-patient management and follow-up. The lessons learned from nonoperative management of pediatric splenic injuries may be applied successfully to medical organ rupture, working in close partnership with hematologists to understand the time course and endpoints for the underlying inflammatory condition.

Postural orthostatic tachycardia syndrome (POTS) is characterized by increased heart rate (HR) with standing and is associated with dizziness, palpitations, and exercise intolerance, with poorly understood mechanisms. To review the literature on cardiorespiratory fitness in POTS, and explore possible determinants of exercise intolerance. Systematic review of studies assessing exercise capacity in POTS. Eligible studies were original prospective and retrospective cohort studies and randomized controlled trials investigating formal exercise assessments (maximal exercise duration with or without gas exchange oxygen consumption (VO) measures) in patients with established POTS using standard criteria. A literature search revealed 199 unique studies, of which we identified 17 cohorts with 1321 subjects with POTS and 502 age- and sex-matched controls. Peak VO was measured in 15 studies and exercise hemodynamics (stroke volume (SV), cardiac output) was measured in 10 studies. Outcome measures were peak VO, gas exchange parameters, and hemodynamics (i.e., HR, SV, cardiac output). All studies described higher HR at standing and submaximal exercise, with earlier peak HR in POTS. Peak VO was reduced in 80% of studies, but only in 30% when matched for deconditioning. Seven of 10 studies (70%) reported reduced SV with standing/exercise versus controls, but only 10% showed reduced cardiac output. Intravenous fluids did not affect hemodynamics or peak VO. Exercise training, as well as propranolol, improved peak VO. Patients with POTS reach peak HR faster. Increased HR accompanies reduced SV, but cardiac output is generally maintained or increased, making it unlikely to cause symptoms. Reducing HR may improve exercise capacity in POTS by delaying peak HR and reducing symptoms.

The COVID-19 pandemic has renewed attention to complex chronic health conditions that challenge conventional biomedical paradigms. Syndromes such as postural orthostatic tachycardia syndrome and myalgic encephalomyelitis/chronic fatigue syndrome have gained broader visibility through the lens of Long COVID. As global vaccination campaigns expanded, a subset of individuals began reporting similarly persistent, multisystem symptoms following COVID-19 immunization-informally referred to as post-COVID-19 vaccination syndrome. These presentations, which include dysautonomia, neuropathic pain, post-exertional malaise, and cognitive dysfunction, resemble post-infectious syndromes and may involve shared immune-related mechanisms. Although no causal relationship to vaccination has been established, these cases-together with comparable reports following other vaccines-highlight limitations in current vaccine safety systems for detecting and evaluating complex chronic outcomes. This article introduces the concept of complex chronic adverse events following immunization (CC-AEFIs) as a pragmatic, surveillance-oriented framework to support the systematic identification and investigation of such cases. CC-AEFIs are not syndromic diagnoses but a higher-order category encompassing persistent, multifactorial conditions that may follow immunization yet challenge existing pharmacovigilance definitions and tools. These conditions often involve multiple organ systems, delayed onset, fluctuating trajectories, diagnostic ambiguity, and symptom heterogeneity. Drawing on the author's lived experience as an affected patient and integrating clinical, regulatory, and experiential evidence, the analysis examines structural and epistemic limitations across the pharmacovigilance continuum-from underrecognition in clinical settings to analytic exclusion and constrained governance. It concludes by proposing reforms to strengthen safety-system responsiveness, including enhanced diagnostic training, longitudinal surveillance, patient-reported outcome integration, and analytic transparency. Addressing these limitations is essential to sustain public trust, ensure equitable care, and uphold the scientific integrity of immunization programs.

The COVID-19 pandemic has resulted in over 776 million confirmed cases worldwide, with post-acute sequelae of COVID-19 now recognized as a significant public health concern. Autonomic dysfunction-including orthostatic intolerance (OI), postural orthostatic tachycardia syndrome (POTS), and orthostatic hypotension (OH)-constitutes a major complication of post-acute sequelae of COVID-19. However, reliable epidemiological estimates remain scarce. As a result, we aim to provide the first global prevalence estimates of autonomic dysfunction in post-acute sequelae of COVID-19. This systematic review and meta-analysis adhered to PRISMA 2020 guidelines, including 21 observational studies. Random-effects models were utilized to estimate pooled prevalence, and sensitivity and meta-regression analyses were conducted to explore heterogeneity. GRADE assessments evaluated evidence certainty. The pooled prevalence estimates demonstrated 70.6% for OI, 36.2% for POTS, and 18.6% for OH. Advancing age exhibited a significant negative association with POTS and OH. In contrast, prolonged post-acute sequelae of COVID-19 duration and female sex showed no significant association with the incidence rates of these conditions. Subgroup analyses indicated higher POTS and OH incidence in mild vs. moderate or severe COVID-19 cases. Publication bias was minimal for OH but evident for POTS. This study provides the first global prevalence estimates of autonomic dysfunction in post-acute sequelae of COVID-19, highlighting its disproportionate burden among younger populations and non-linear temporal trends. The findings advance epidemiological understanding and inform evidence-based public health strategies to address post-COVID complications. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=556546, PROSPERO CRD42024556546.

Patients with postural tachycardia syndrome report position-dependent visual symptoms. Despite their impact on daily life, these symptoms have remained largely unexplored in research. The aim of this study was to investigate the nature of visual symptoms in postural tachycardia syndrome and possible underlying pathophysiological mechanisms. Fifteen patients with postural tachycardia syndrome and 15 healthy controls were included in the study. Through a comprehensive array of measurements, including haemodynamics, subjective symptom assessments, eye movement tracking and pupil diameter analysis, participants were assessed during free image exploration in both supine and 60° head-up tilt positions. During head-up tilt, patients showed a decreased number and duration of fixations, as well as a decreased number, peak velocity and amplitude of saccades compared to the supine position and the control group. This reduction in visual exploration occurred primarily in the peripheral field of view and coincided with the occurrence of subjective visual symptoms. No significant differences in the saccade main sequence were observed between the two groups in either body position. Patients with postural tachycardia syndrome have a reduced exploration of the peripheral field of view when in an upright body position, potentially leading to tunnel vision. Since the normality of the saccade main sequence in patients combined with the focus on the centre of the field of view and the lower saccade amplitudes points to an intact brainstem function, the decrease in peripheral visual exploration may be attributed to a position-dependent dysfunction of the frontal eye field.

A high prevalence of disorders of gut-brain interaction (DGBI) exist in patients with hypermobile Ehlers-Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD). However, it is unknown if clusters of hEDS/HSD patients exist which overlap with different DGBIs and whether this overlap influences presence of comorbidities and quality of life. We aimed to study these knowledge gaps. A prospectively collected hEDS/HSD cohort of 1044 individuals were studied. We undertook Uniform Manifold Approximation and Projection-enabled (UMAP) dimension reduction to create a representation of nonlinear interactions between hEDS/HSD and DGBIs, from which individuals were stratified into clusters. Somatization, Postural Tachycardia Syndrome (PoTS), autonomic symptoms, psychological factors and quality of life were statistically compared between clusters. The mean age of patients was 40 ± 13.2 years; 87.8% were female. Patients segregated into three clusters: Cluster 0 (n = 466): hEDS/HSD+ functional foregut disorders (FFD) + irritable bowel syndrome (IBS); Cluster 1 (n = 180): hEDS/HSD+ IBS and Cluster 2 (n = 337): hEDS/HSD alone. In cluster 0, we demonstrated increased somatization (p <0.0001), anxiety (p <0.0001), depression (p <0.0001), PoTS prevalence (p = 0.003), autonomic symptoms (p <0.0001) and reduced quality of life (p <0.0001) compared to cluster 2. Cluster 0 had greater comorbidity burden than cluster 1. Within hEDS/HSD, subgroups exist with a high prevalence of FFD and IBS. These subgroups have a higher prevalence of psychological disorders, dysautonomia and poorer quality of life compared with hEDS/HSD alone. Further research should focus on healthcare utilization, management and prognosis in hEDS/HSD and DGBI overlap.

Compression garments reduce heart rate and symptoms in patients with postural orthostatic tachycardia syndrome in an acute laboratory setting. Patients taking medications controlling heart rate have less benefit from compression than those not on medications. The effectiveness of commercially available garments in a community-based setting, with and without medication use, is not known. The authors sought to evaluate commercially available compression tights in a community-based setting both with, and without, medications modulating heart rate, using a clinical trial with 2 before-after protocols conducted in a randomized crossover fashion. Participants (N = 26) held medications during protocol #1 and took medications as normal during protocol #2. For each, participants completed 4, 10-minute active stand tests in the morning (AM) and afternoon (PM) with the garments on (ON) and off (OFF) (AM-OFF, AM-ON, PM-ON, and PM-OFF). Heart rate (Holter monitor) and symptoms (Vanderbilt Orthostatic Symptom Score [VOSS]) were measured for each standing test. Protocol #1: Standing heart rate was reduced (105 [99-116] beats/min vs 119 [105-130] beats/min; P < 0.001) and symptoms improved (P < 0.001), during AM-ON vs AM-OFF. Standing heart rate (P = 0.04) and symptoms (P = 0.004) increased when compression was removed after several hours. Protocol #2: Standing heart rate was reduced (84 [77-90] beats/min vs 89 [84-100] beats/min; P < 0.001), and symptoms improved (P = 0.03), during AM-ON vs AM-OFF. Standing heart rate (P = 0.02) and symptoms (P < 0.001) increased when compression was removed after several hours. Commercially available compression tights reduced heart rate and symptoms both acutely and after several hours of use. This additional benefit persisted whether concomitant medications were used. (Compression Garments in the Community With POTS [COM-COM-POTS]; NCT04881318).

Orthostatic intolerance is the name of the disease in Europe and the United States; however, in Japan, it is commonly known as orthostatic dysregulation (OD). OD is a physical disorder caused by failure of the body's compensatory regulatory mechanism to adapt to changes in circulatory dynamics during orthostasis; however, in many cases, the influence of psychosocial factors has been noted. The mother-child relationship is a major psychosocial factor in children, and it has been reported that parent-child patterns associated with OD are often excessive parental interference and child over-adaptation. This study focused on the psychological and physical factors of OD and assessed the parent-child relationship patterns among children with postural tachycardia syndrome (POTS), a subtype of OD, and examined how they relate to the child's personality traits and autonomic neuron function. A total of 36 six children diagnosed with POTS (mean age 13.5 ± 0.9 years) were compared with the results of the following questionnaires on parent-child relationships, personality traits, and the autonomic neuron function test: Family diagnostic test (a diagnostic test of parent-child relationship) for mothers and children, AN-EGOGRAM (the egograms that can be adapted to childhood and adolescence, when the ego is in the process of developing and growing), and a frequency analysis of heartrate and blood pressure variability for the children. Assessments of the mother-child relationship patterns among children with POTS found significant associations between maternal "strict discipline" and children's negative feelings, excessive parental intervention and children's susceptibility to stress, and the degree of children's "feeling of rejection" and lower supine vasomotor sympathetic nerve activity. The findings also suggested that children with POTS typically exhibited lower scores in critical parent and free child personality traits, but higher scores in adapted child (AC). Notably, mothers of children with high AC scores reported less dissatisfaction with their spouses regarding childcare. In the parent-child relationship in POTS, an association was observed between maternal "strict discipline" and children's negative feelings, suggesting that a less strict disciplinary approach may contribute to a more positive parent-child relationship.

Abdominal compression is an effective nonpharmacological treatment for orthostatic intolerance. Although the efficacy of abdominal compression bands has been studied in adults, studies involving children are limited. This study investigates the efficacy of abdominal compression bands in children diagnosed with postural tachycardia syndrome (POTS), using a larger cohort and incorporating autonomic nervous function assessment via frequency analysis. A crossover study was conducted with 23 patients with POTS (mean age 13.4 ± 0.8 years), with and without abdominal compression bands (20 mmHg). Standing symptoms, hemodynamics (blood pressure, heart rate [HR], cardiac index [CI], stroke volume [SV], and total peripheral resistance [TPR]), and cardiovascular autonomic function were assessed by spectrum analysis during standing tests. These variables were compared with and without bands. When standing with the abdominal compression band, subjective symptoms improved, increases in heart rate (HR) and decreases in stroke volume (SV) were suppressed, blood pressure was maintained, and cardiac parasympathetic function was improved. By contrast, in the supine position, patients showed an increased HR, decreased CI, increased TPR, lower cardiac parasympathetic function, and higher cardiac sympathetic function. Abdominal compression bands may relieve symptoms while standing and improve hemodynamic and autonomic nervous functions in children with POTS.

Postural Tachycardia Syndrome (POTS) is a chronic condition characterized by orthostatic intolerance and a significant rise in heart rate upon standing. Patients often experience debilitating symptoms, such as brain fog and chronic fatigue, which hinder daily functioning. Non-pharmacological management strategies, particularly pacing, are crucial for reducing symptom fluctuations and improving quality of life. Heart rate monitoring plays a key role in effective pacing, enabling patients to plan activities and prevent severe symptom onset. Recent technological advancements have increased interest in wearable devices for managing chronic conditions. This study examines the feasibility of using wearable technology to support symptom management in POTS patients. Through an Exploratory- Descriptive Qualitative approach, five key themes emerged, including personalized management strategies and the beneficial impact of real-time feedback. The findings suggest that wearable devices can enhance self-management, improve communication with healthcare providers, and empower patients to take a more proactive approach to their care.

Postural tachycardia syndrome (PoTS) is a chronic condition characterized by an increased heart rate upon standing and is recognized to be associated with dizziness and migraines. This study aimed to investigate the multifaceted nature of dizziness in PoTS from a vestibular perspective, including the relationship with vestibular migraine. A retrospective review of 80 patients with confirmed PoTS, attending a tertiary neuro-otology clinic, was conducted to evaluate standardized detailed assessments {validated symptom questionnaires, history/physical examination, neuro-otological diagnostics [including video head impulse test (VHIT), videonystagmography (VNG), and caloric testing], and management}. The PoTS cohort was also compared with an age- and sex-matched control group of dizzy patients. A total of 80 patients were included (mean age: 35.3 years ± 12.1; 93% women). Approximately 84% had migraine, and 30% had vestibular migraine. Clinical examination of static and dynamic balance was most frequently abnormal. VHIT was abnormal in 2%, and VNG canal paresis and directional preponderance were abnormal in 19 and 22%, respectively. In total, 49% of cases were offered migraine management advice, and 58% were offered vestibular rehabilitation. The PoTS group showed higher rates of vestibular symptoms, including vertigo, unsteadiness, and positional vertigo, and high Disability Rating Scale (DRS) scores. Our findings reflect the challenges of distinguishing dizziness phenotypes in PoTS, particularly vestibular migraine. This study illustrates the importance of judicious clinical enquiry to investigate non-orthostatic dizziness mechanisms, such as vestibular migraine, for which evidence-based management exists, and recommends further research to elucidate the multifaceted nature of PoTS-associated dizziness.

Postural Orthostatic Tachycardia Syndrome is characterized by an excessive increase in heart rate during postural changes without significant blood pressure alterations, often accompanied by symptoms such as dizziness, fatigue, and palpitations. While prior studies have explored potential mechanisms, the precise etiology and pathological basis of Postural Orthostatic Tachycardia Syndrome remain unclear, leading to treatments focused on symptom management rather than addressing root causes. This study employs a hemodynamic fluid-structure interaction model (using existing clinical data) to investigate the roles of hypovolemia, vascular dysfunction, and autonomic nervous system dysregulation in Postural Orthostatic Tachycardia Syndrome pathogenesis. Computational results revealed that hypovolemia reduces cerebral blood flow by approximately 100 mL/min due to a 30% decrease in blood volume, while vascular dysfunction-marked by a 50-100% increase in arterial stiffness-further diminishes cardiac output and cerebral perfusion. These conditions trigger compensatory tachycardia through autonomic feedback mechanisms. Our findings demonstrate that an insufficient cerebral blood supply, driven by hypovolemia and impaired vascular compliance, combined with autonomic dysregulation, underlies the hallmark tachycardia in Postural Orthostatic Tachycardia Syndrome. This mechanistic insight provides a foundation for targeted therapeutic strategies, emphasizing the need to address blood volume management, vascular elasticity, and autonomic balance to improve clinical outcomes.

Postural orthostatic tachycardia syndrome (POTS) is a disorder with cardiovascular autonomic dysfunction where multiple and variable symptoms are common, including those from the peripheral and enteric nervous systems. We aimed to investigate subjective and objective signs of small and large fiber neuropathy in a Swedish POTS cohort compared with healthy controls. Secondly, we wanted to examine potential associations between gastrointestinal symptoms and neuropathy signs in POTS. Forty-three patients with POTS (93% female) and 54 healthy controls (76% female) were included in the study. All participants completed a questionnaire including modified neuropathy symptoms score (NSS) and irritable bowel syndrome severity scoring system (IBS-SSS) for gastrointestinal evaluation. Small nerve fibers were investigated by assessing the intraepidermal nerve fiber density (IENFD). Large nerve fiber function was examined through pinprick and vibration perception thresholds (VPTs), using neurothesiometry and multi-frequency vibrometry (MFV). The patients were classified as "High NSS" and "High IBS-SSS" if their total NSS vs. IBS-SSS were above median levels in POTS. Peripheral sensory and gastrointestinal symptoms were more prevalent and severe in POTS than in controls. Median VPTs were normal and IENFDs were comparable between POTS and controls (2.26 [1.62-3.08] vs. 1.63 [0.73-2.68] fibers/mm; p = 0.108). The patients with "high NSS" had slightly higher VPTs measured by MFV, although within normal ranges, compared to patients with "low NSS". The patients within the "high IBS-SSS" group had higher NSS (18.0 [14.3-22.8] vs. 11.0 [4.0-15.0]; p = 0.002) compared to patients with low total IBS-SSS. Symptoms of peripheral and enteric neuropathy are common in POTS but no solid evidence was found regarding functional or morphological signs of small or large fiber neuropathy. Neuropathic and gastrointestinal symptoms were closely associated within POTS.