Patients with Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Intolerance (OI) commonly present with symptoms suggestive of Pelvic Venous Disorders (PeVD). The presence of PeVD may contribute to orthostatic symptoms in these patients due to venous obstruction with stasis and pooling. Iliac vein compression, a PeVD, has historically been treated with iliac venous stenting. The authors hypothesize that patients with POTS frequently have findings of PeVD, that venous outflow obstruction from iliac vein compression exacerbates POTS/OI symptomatology, and that treating PeVD improves POTS/OI symptoms. This paper reports results from two studies at two different institutions with a partially overlapping patient population. The first was a retrospective cross-sectional observational study of patients with POTS/OI who presented to Emory University Cardiology (Atlanta, GA, USA) from October 2019 to June 2023. We aimed to evaluate the prevalence of concurrent POTS/OI and PeVD using screening pelvic venous ultrasound, MR and/or CT, compared to venogram with intravascular ultrasound (IVUS). We secondarily evaluated the efficacy of each imaging modality in screening accuracy for PeVD. The second study was a retrospective review of medical records for 271 female patients with POTS/OI who received treatment of PeVD with iliac vein stenting from June 2019 to November 2024 at Minimally Invasive Procedure Specialists (Highlands Ranch, CO). The primary objective of this study was to explore quality of life (QoL) outcomes in female patients with POTS/OI before and after treatment. The secondary objective was to record the prevalence of associated pelvic pain, systemic symptoms, and response to therapy in this population. In the first cohort, 129 patients (84% cis female) with a diagnosis of POTS/OI and symptoms of PeVD were assessed by standard imaging for venous pathology. 107 patients (83%) had confirmed pelvic venous compression (iliac vein, renal vein, or both) or pelvic venous congestion on imaging with at least one screening modality. All screening modalities were relatively insensitive in detecting iliac venous compression compared with venography and IVUS. In the second cohort, following iliac vein stenting, significant improvements were seen in Orthostatic Hypotension Questionnaire (OHQ) composite scores at three months (p < 0·001) and at 12 months (p < 0·001). The OHQ Symptom Assessment (OHSA) and Daily Activities Scale (OHDAS) subscores, International Pelvic Pain Society (IPPS) score, Pelvic Congestion Syndrome (PCS) score, Pelvic Pain and Urgency/Frequency Symptom Scale (PUF) score, and Ancillary symptom score all demonstrated statistically significant decreases at three months that persisted at 12 months (all p < 0·001) as well. The high prevalence of PeVD in POTS/OI patients suggests an association between the two diagnoses. In the absence of expert clinical review, screening with US, CT, and MR may not be sufficient to rule out PeVD. Significant improvements were seen in QoL in patients with POTS/OI and PeVD who underwent iliac vein stenting. These results call for additional trials to examine the clinical and hemodynamic effects of venous stenting on POTS/OI symptomatology and associated systemic symptoms, including pelvic pain. These studies received no funding.

The association between blood pressure variability (BPV) or heart rate variability (HRV) and the baroreflex is well established. However, the role of the vestibular-autonomic reflex in regulating BP and HR stability has primarily been explored only in experimental studies. We aimed to delineate the association of BPV and HRV with otolith function in postural orthostatic tachycardia syndrome (POTS). We retrospectively analyzed data from consecutive patients with POTS recruited between April 2021 and April 2025 at a tertiary referral-based hospital in South Korea. All patients underwent a head-up tilt table test using a Finometer device and cervical (cVEMP) and ocular vestibular evoked-myogenic potentials (oVEMP). The Finometer data were analyzed using a power spectral analysis. The Finometer, cVEMP, and oVEMP data were compared with those of 32 age- and sex-matched healthy participants. A total of 47 patients with POTS (mean age standard deviation [SD] = 33 10 years; 30 female patients) and 32 age- and sex-matched healthy participants were included for analysis. The n1-p1 amplitude of oVEMP was larger in patients with POTS than in healthy participants (p = 0.002). p13 latency was negatively correlated with the SD of heart rate in the supine position in patients with POTS (p = 0.001), a trend not observed in healthy participants. The n1-p1 amplitude (odds ratio [95% confidence interval] = 1.27 [1.08-1.49], p = 0.004) and root mean square of successive differences (RMSSD) during tilting (0.82 [0.72-0.93], p = 0.001) were associated with POTS after adjusting for other covariates. Otolithic function may play a role in accentuating BPV and HRV in POTS by contributing to enhanced sympathetic outflow.

Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among this patient population. The purpose of this mixed-methods study was to provide greater understanding of the perceived barriers, preferences, perceptions of exercise, and experiences implementing exercise recommendations for adults with POTS in order to optimize treatment recommendations and intervention design. This study consisted of a series of focus groups (n = 29) and an online survey of adults with POTS (n = 255) focusing on exercise engagement, beliefs, barriers, and facilitators. Qualitative data were analyzed using an iterative inductive-deductive approach, informed by social cognitive theory, which resulted in a conceptual framework and a series of themes. Survey results showed that participants reported a wide range of exercise frequency prior to the onset of POTS symptoms, and overall lower exercise engagement post-POTS. In both survey results and qualitative findings, participants reported believing that exercise is important in managing POTS, but identified barriers to exercise training, including most saliently, their symptom burden. Participants also identified important needs and facilitating factors that could support them in engaging in regular exercise to help manage their condition. These findings shed light on the patient experience of exercise in POTS, which can inform both the tailoring of exercise recommendations and the design of interventions to support exercise engagement specific to the POTS population.

Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing. The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review. Evidence on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.

Twenty five percent of children who sustain a mild traumatic brain injury (mTBI) or concussion experience persisting post-concussion symptoms (PPCS). The symptoms of PPCS significantly overlap with postural orthostatic tachycardia syndrome (POTS). We aimed to review the literature and investigate the prevalence of POTS in children and adolescents recovering from mTBI. This single centre controlled cross-sectional cohort study recruited children (aged 8-18 years inclusive) diagnosed with mTBI in the emergency department. At 4-6 weeks postinjury, children completed the Active Stand Test. The primary outcome was change in heart rate alongside clinical symptoms consistent with POTS. A total of 113 participants (64 PPCS, 24 mTBI with no clinical symptoms [asymptomatic], and 25 healthy controls) of similar age (mean 13.9 years) and sex (n = 55 [48.7%] male) underwent orthostatic testing. There were no significant group differences in heart rate or blood pressure at baseline, or within 10 minutes of standing. Three (4.8%) symptomatic participants satisfied POTS diagnostic criteria, compared to zero asymptomatic and one (4.2%) control participant. Using the Active Stand Test, a small proportion of children with PPCS satisfied clinical POTS criteria. Although it should be considered in the differential diagnosis, POTS is not common nor overrepresented in PPCS.

BackgroundIndividuals with neurologic impairment, such as brain injury, are more likely to have autonomic dysfunction, including POTS, but often experience a lack of treatment options and access to quality care.ObjectiveExamine the feasibility and outcomes of a group-based multimodal rehabilitation training program.MethodsNineteen females, ages 18-53 (M = 28.6) completed the outpatient training program. The intervention included eight 50-min weekly sessions using an interdisciplinary, multimodal approach, including education, movement, and mindful self-compassion. Participants completed demographic and medical history and assessment for baseline orthostatic intolerance. At pre-training, post-training, and follow-up, participants completed the Modified Fatigue Impact Scale (MFIS), Lower Extremity Functional Scale (LEFS), Rand 36-Item Health Survey 1.0 (RAND-36), Trail Making Test (A and B) (TMT-A, TMT-B), 10-Meter Walk Test (10MWT), and grip strength testing.ResultsAt baseline, participants were significantly below norms in daily function (p < 0.001), grip strength (p ≤ 0.001) gait speed (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Between pre-training and follow-up, participants showed significant improvement across function in daily life tasks (p < 0.01); grip strength in the dominant (p < 0.01) and non-dominant (p < 0.01) hands; gait speed (p < 0.05); levels of fatigue (p < 0.05); cognitive performance (p < 0.05); and quality of life (p < 0.05).ConclusionIndividuals with POTS face functional challenges that can be significantly and objectively improved through multimodal rehabilitation. There is a need for provider education and further research to optimize care and quality of life for individuals with POTS.

Postural Orthostatic Tachycardia Syndrome (POTS) is a debilitating condition of the autonomic nervous system with no clear referral, diagnosis, and treatment pathways. Patients experience high levels of symptoms and moderate levels of distress. The purpose of this study was to explore biopsychosocial factors associated with distress in those under investigation for POTS, to identify potential targets for intervention. A longitudinal, quantitative survey. Participants (n = 149) completed demographic, psychosocial, and symptom questionnaires prior to a diagnostic POTS clinic visit and 6 months follow-up (n = 98). Correlation and regression analyses were used to identify factors associated with distress at baseline (within one month before diagnostic hospital visit) and at 6 months follow up. At baseline, distress levels were moderate and greater symptom focusing, all-or-nothing and avoidance behaviours, threatening views of the illness, emotional reactivity, cardiac anxiety, POTS symptoms, number of specialists seen, lower social support, and younger age were significantly associated with higher levels of baseline distress. The baseline regression model including all demographic, clinical, and psychosocial factors explained 61.2 % of the variance in distress, with the psychosocial variables collectively explaining 55.6 % of this variance (F = 11.06, p < .001). There was no significant difference between distress levels at baseline and follow-up. Psychosocial variables explained 4.7 % of the variance (F = 0.76, p = .665) in changes in distress scores over 6 months. Baseline distress scores accounted for the vast majority of variance in distress at follow-up. This study identified key novel psychosocial factors that were significantly associated with distress which could be potential targets for intervention. Additional factors such as younger age and a higher number of specialists seen were also associated with higher levels of distress, which merits attention when assessing patients' psychological wellbeing this patient group. Distress levels did not significantly change following the specialist consultation and investigation.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with challenging diagnosis and management. This cross-sectional, multi-national, web-based physician chart audit described clinical features and management of POTS, offering insights into disease burden and outcomes before and after the COVID-19 pandemic. Physicians (n = 153), primarily cardiologists (77.1 %), reported data from 599 patients from two cohorts: 1) POTS not triggered by COVID-19 (n = 361) and 2) POTS triggered by COVID-19 (n = 238). Overall, most patients experienced POTS symptoms onset between the ages of 18 and 39 years (33 %), with 13 % presenting symptom onset before 18 years of age. Over 70 % had at least one pre-existing medical condition. Most patients underwent 5-8 tests to define POTS diagnosis. Around 80 % received incorrect diagnoses before POTS confirmation, and 25 % waited over a year for diagnosis. Although some patients showed reduction in symptom severity over time, symptoms were still persistent at last consultation. Non-pharmacological interventions were common in the first treatment line. In subsequent lines, there was an increase in pharmacological treatments, with beta-blockers and ivabradine being the most frequently prescribed medications. Comparative analysis between pre- and post-COVID-19 POTS showed that while POTS patients triggered by COVID-19 were somewhat older and had fewer comorbidities, differences were not clinically meaningful, suggesting similar diagnostic, management and treatment patterns. Regional differences in diagnoses and treatment patterns were observed between US and Europe. This study highlights the challenges faced by POTS patients, while providing insights into the diagnostic and treatment approaches in real-world settings.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder mainly of orthostatic intolerance, often accompanied by a spectrum of symptoms related to autonomic nervous system dysfunction. Although the diagnostic criteria require an orthostatic challenge test, the associated symptom burden can be broad and is often missed by treating healthcare professionals, resulting in significant diagnostic delay. Treatment of this highly heterogenous condition is nuanced and consists of non-pharmacologic and pharmacologic approaches. Availability of POTS care is limited, with a dearth of medical specialists or general practitioners specialising in autonomic medicine. The complexity of care for those with POTS necessitates a multidisciplinary approach due to the need for extended appointment times and frequent follow-ups to monitor therapeutic response and progress. This should include a primary team consisting of a general practitioner and trained autonomic physicians with specialist nurses, allied health professionals, and any other specialists required to manage the affected systems. This state-of-the-art review aims to cover the key aspects of diagnosing and managing POTS, including special neurological, gastroenterological, psychological, and paediatric considerations. There is an urgent need to provide services that meet the needs of the growing POTS population.

A previous study showed a high prevalence of central sensitization syndrome (CSS) in patients with autonomic symptoms. The prevalence of CSS in postural tachycardia syndrome (POTS), a form of dysautonomia, is unknown. To analyze the prevalence of CSS in POTS. This case-control study included patients with a POTS diagnosis confirmed by autonomic testing at Brigham and Women's Faulkner Hospital between 2022 and 2025. Data were analyzed from April to August 2025. POTS with and without CSS. Central Sensitization Inventory (to assess central sensitization syndrome [CSS]), COMPASS-31 (autonomic symptoms), Neuropathy Total Symptom Score-6 (NTSS-6, sensory symptoms), PROMIS (global health), and autonomic testing (Valsalva maneuver, deep breathing, sudomotor function, and head-up tilt) with skin biopsies. Primary outcome was the central sensitization inventory score with secondary outcomes individual test performances. This study included 305 patients with POTS, of whom 264 (86.6%) met criteria for CSS (mean [SD] age, 33.21 [10.75] years; 30 males [11.4%]; 234 females [88.6%]). Patients with CSS compared with those without CSS had longer duration of symptoms, were more frequently female, exhibited higher rates of anxiety (195 [73.9%] vs 20 [48.8%]; P = .002), depression (168 [63.6% vs 14 [34.1%]; P = .001), fibromyalgia (46 [17.4%] vs 0 [0%]; P = .008), irritable bowel syndrome (IBS, 90 [34.1%] vs 7 [17.1%]; P = .046), headaches (176 [66.7%] vs 12 [29.3 %]; P < .001), treatment with antihistamine medication (136 [51.5%] vs 13 [31.7%]; P = .03), psychiatric medication (163 [61.7%] vs 17 [41.5 %]; P = .02), pain medication (127 [48.1%] vs 8 [19.5%]; P = .001), and gastrointestinal medication (82 [31.1%] vs 5 [12.2 %]; P = .02), and had higher COMPASS-31 scores (51.93 [13.23] vs 31.18 [10.49]; P < .001), NTSS-6 scores (11.32 [4.86] vs 4.44 [3.32]; P < .001), NRS scores (3.26 [2.73] vs 0.54 [1.21]; P < .001), and worse PROMIS scores (20.36 [5.45] vs 27.96 [4.73]; P < .001). Autonomic tests showed lower orthostatic end-tidal carbon dioxide (27.59 [6.39] mm HG vs 29.46 [4.68] mm HG; P = .002) and a greater orthostatic decline in cerebral blood flow velocity (17.08 [8.72] cm/sec vs 13.68 [5.04] cm/sec; P < .001) in the CSS group. Both groups had similar prevalence of autonomic failure (223 [84.5%] vs. 33 [80.5%]; P = .67, mostly mild intensity), and abnormal skin biopsy (43% in both groups). These findings suggest that CSS was common in patients with POTS and may represent a higher-order sequela of cerebrovascular, respiratory, and autonomic dysregulation. This heightened central processing may amplify symptom perception through altered interoceptive signaling. Central sensitization and autonomic impairment may coexist, and management should focus on both conditions.

A significant number of physicians are unclear of the vast clinical manifestations of dysautonomia and imbalance of the autonomic nervous system, specifically the parasympathetic and sympathetic nervous systems. The major obstacle has been an inability to determine the mechanism of action as well as multisystem dysfunction and a lack of clear-cut testing. Dysautonomia, a pathophysiological malfunction of the sympathetic and parasympathetic nerves in our bodies, can present as altered clinical functions of heart rate (tachycardia/bradycardia), altered breathing patterns, blood pressure (hypertension/hypotension), sweating, digestion, syncope, etc. These symptoms have caused specialists to miss this diagnosis because of relative nonspecificity. Our current analysis of patients demonstrates significant delays in diagnosis, misdiagnosis, and the development of chronic syndromes because of the above. We demonstrate that monitoring of heart rate and blood pressure with changes in position and respiration can be easily and quickly performed without orthostatic stress and can demonstrate the entities of sympathetic withdrawal, cholinergic excessive aspects as well as tachycardia, blood pressure dips with posture, etc. This analysis takes less than an hour without the need for injections or medication, thus more quickly informing the cardiologist/neurologist of the correct diagnosis. We will attempt to demystify these issues so that clinicians and the scientific community will have a better understanding of this entity and consider a diagnosis of dysautonomia earlier in the differential diagnostic process and start treatment approaches sooner.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating disorder characterized by excessive increases in heart rate upon standing and poor orthostatic tolerance. Impairments in large artery, endothelial, and venous function may collectively, or individually, result in excessive blood pooling and impaired venous return, or other inadequate vascular response to standing, thus contributing to POTS. Herein, we tested the hypothesis that patients with POTS would exhibit reduced large artery stiffness, enhanced endothelial function, and greater lower limb venous pooling while standing, compared with healthy controls. Fourteen participants with a clinical diagnosis of POTS and 15 age-matched controls (all females; median age [interquartile range]; 21 [19-37] yr, = 0.769) were recruited. Central arterial stiffness was determined using carotid-femoral pulse wave velocity (cfPWV; SphygmoCor). Endothelial function was assessed using brachial artery flow-mediated dilation (FMD) following a 5-min forearm occlusion at 200 mmHg. Functional measures of calf venous volume and filling time (90% maximal venous filling) were acquired (air plethysmography) while standing. cfPWV was increased in people with POTS [(means ± SD) 5.5 ± 0.9 vs. 4.8 ± 0.4, = 0.031], whereas FMD was not different between groups ( = 0.854). During standing, calf venous volume was 29% greater in people with POTS ( = 0.048), and venous filling time was almost twice as long (404 ± 199 vs. 207 ± 99 s; = 0.003). These findings indicate that people with POTS exhibit increased central arterial stiffness, preserved endothelial function, and increased calf venous filling during standing. Such differences in lower limb venous filling dynamics on standing likely contribute to the orthostatic intolerance that characterizes POTS. Females with POTS and age-matched healthy controls underwent assessments of central arterial stiffness, endothelial function, and calf distensibility. Pulse wave velocity was higher in people with POTS, but brachial artery flow-mediated dilatation was not different between groups. Standing calf volume was greater in people with POTS, and maximal filling times were twice as long, suggesting altered venous and/or microvascular function. Augmented venous pooling in patients with POTS may impair venous return and orthostatic tolerance.

Autoimmune autonomic disorders are common, though often under-recognized, and suboptimally understood. Autonomic nervous system impairment may result from immune-mediated damage to central or peripheral autonomic pathways, and typically involve both sympathetic and parasympathetic systems, as well as the enteric nervous system. Various autoimmune conditions may primarily involve the autonomic nervous system, as in autoimmune autonomic ganglionopathy associated with ganglionic nicotinic acetylcholine receptor antibodies or may involve autonomic systems as part of a multisystem neurologic process with or without underlying malignancy, or autonomic nerves may be targeted in systemic autoimmunity as is seen with Sjögren's syndrome. A careful history and diagnostic evaluation is necessary to determine the type, distribution, and severity of dysautonomia; which may be generalized or more restricted in nature. An understanding of potential autonomic features in the various autoimmune autonomic disorders can help to provide diagnostic clarity, and recognition of autonomic signs and symptoms is necessary to direct symptomatic and immunotherapeutic decisions in these patients.

Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are relatively common and disabling multisystem disorders that share overlapping features, including post-infectious onset and similar clinical manifestations such as brain fog, fatigue, muscle pain, and dysautonomia with orthostatic intolerance. These similarities suggest that Long COVID and ME/CFS may share common pathophysiological mechanisms, though the underlying mechanisms remain poorly understood, partly due to the difficulty in quantifying many of the symptoms. This retrospective study evaluated Long COVID and pre-COVID ME/CFS patients who completed autonomic testing between 2018 and 2023 at the Brigham and Women's Faulkner Hospital Autonomic Laboratory. The evaluations included autonomic tests (Valsalva maneuver, deep breathing, tilt-table test, and sudomotor function) with capnography and transcranial Doppler monitoring of cerebral blood flow velocity (CBFv) in the middle cerebral artery, neuropathic assessment through skin biopsies for small fiber neuropathy (SFN), invasive cardiopulmonary exercise testing (ICPET), and laboratory analyses covering metabolic, inflammatory, autoimmune, and hormonal profiles. A total of 143 Long COVID and 170 ME/CFS patients were analyzed and compared to 73 healthy controls and 290 patients with hypermobile Ehlers-Danlos syndrome (hEDS). Tests revealed extensive similarities between Long COVID and ME/CFS, including reduced orthostatic CBFv (92%/88% in Long COVID/ME/CFS), mild-to-moderate widespread autonomic failure (95%/89%), presence of SFN (67%/53%), postural tachycardia syndrome (POTS) (22%/19%), neurogenic orthostatic hypotension (15%/15%) and preload failure (96%/92%, assessed in 25/66 Long COVID/ME/CFS). Patients with hEDS exhibited more severe peripheral neurodegeneration compared to the other groups. Laboratory tests did not distinguish between the conditions. Both Long COVID and ME/CFS demonstrate dysregulation in cerebrovascular blood flow, autonomic reflexes, and small fiber neuropathy, suggesting that these conditions may share a common underlying pathophysiology. However, differing distributions of findings in patients with hEDS raise the question of whether these conditions represent distinct but overlapping syndromes or reflect a shared underlying pathway. Further research is required to clarify the relationship between these conditions and the potential underlying pathophysiological mechanisms.

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic disorder characterized by chronic (> 3 months) orthostatic intolerance and an increase in heart rate (HR) of ≥ 30 beats per minute (bpm) without orthostatic hypotension. Traditional diagnostic approaches, such as the active standing or tilt-table test, are typically conducted under controlled clinical conditions, limiting their ability to capture the natural variability of symptoms and the intricate physiological responses occurring in daily life. These tests may cause patient discomfort, dizziness, nausea, or syncope. Furthermore, they are timeconsuming and cannot be used as a screening tool for POTS. To address these limitations, this study explored wearable devices that continuously collect physiological data-specifically, electrocardiogram (ECG) and accelerometer (ACC)-derived metrics-from POTS patients and healthy controls during routine daily activities. Physiological features around posturechange events identified in the data were processed and used to train and test a baseline deep learning model. The model demonstrated promising performance in accurately differentiating POTS patients from healthy controls in a relatively small cohort (66 from POTS patients and 20 from controls), indicating its potential as a feasibility study for clinical decision support. Future studies involving larger and more diverse samples under varying clinical conditions would be necessary to enhance the robustness and viability of our diagnostic model.

Abdominopelvic Vascular Compression Syndrome(s) (VCS) are rare disorders with diverse symptoms that appear to occur more frequently in patients with Ehlers-Danlos Syndrome (EDS) and Hypermobility Spectrum Disorder (HSD). The reported associations between EDS/HSD, Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS) further complicate the diagnosis and management of the VCS in this specific patient population. This review summarises the established literature on this complex topic, highlighting these relationships, with the aim to propose a framework for recognising and managing VCS among patients with EDS/HSD. Given the limited body of literature on this topic, we also aim to underscore the need for further research within this specific patient population. A PRISMA-guided systematic review was conducted using PubMed and Ovid/Medline databases. VCS included Median Arcuate Ligament Syndrome (MALS), Superior Mesenteric Artery Syndrome (SMAS), Nutcracker Syndrome (NCS), and May-Thurner Syndrome (MTS). Given the limited number of studies, small cohort studies and case reports/series were also reviewed. Of 183 screened studies, 62 met the inclusion criteria. Only six studies directly addressed the VCS in EDS/HSD. Five discussed an EDS-POTS association, two described links between MCAS, POTS, and EDS, and five associated POTS with VCS. Only one study explored all four conditions. Evidence suggests an association between EDS/HSD, VCS, POTS, and MCAS but remains limited. Underdiagnosis and delayed treatment are common and underscore the need for multi-disciplinary care. Invasive imaging and interventions appear generally safe in EDS/HSD, excluding vascular EDS, yet robust safety and outcome data and tailored diagnostic or treatment algorithms are lacking and require further investigation.

The aim of the study was to clarify the cause of orthostatic dysregulation in Japanese children by analyzing fluctuations in adenylate cyclase activity. Four types of orthostatic dysregulation in Japan include postural orthostatic tachycardia syndrome, delayed orthostatic hypotension, immediate orthostatic hypotension, and vasovagal syncope. However, the exact cause of these disorders remains unknown. To identify the cause of these conditions, we examined the resting blood adenylate cyclase activity and basic clinical data (blood pressure, pulse rate) of 30 patients diagnosed with orthostatic dysregulation (21 postural orthostatic tachycardia syndrome, eight delayed orthostatic hypotension, one immediate orthostatic hypotension, zero vasovagal syncope) and 20 previously reported healthy adults. The results of this study showed that adenylate cyclase activity (isoproterenol and adrenaline) in patients with postural orthostatic tachycardia syndrome was significantly higher than that in patients with delayed orthostatic hypotension and healthy adults. Moreover, patients with postural orthostatic tachycardia syndrome had significantly higher values than healthy adult controls at all five concentration points. Adenylate cyclase activity in patients with delayed orthostatic hypotension showed a trend toward higher values at 10 μM of adrenaline. Furthermore, owing to the higher adenylate cyclase activity in patients with postural orthostatic tachycardia syndrome, their systolic blood pressure was higher than that in patients with delayed orthostatic hypotension. These results suggest that increased adenylate cyclase activity may be related to the onset of orthostatic dysregulation (postural orthostatic tachycardia syndrome and delayed orthostatic hypotension). In conclusion, adenylate cyclase activity levels may be related to the onset of orthostatic dysregulation, and this can be used as a new strategy for diagnosing orthostatic dysregulation.

hypermobile spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are connective tissue disorders often associated with systemic manifestations such as mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS), irritable bowel syndrome (IBS), and autoimmune conditions, including spondyloarthritis (SpA). The overlap of these conditions complicates diagnosis and treatment. This study investigates the prevalence of MCAS and other comorbidities, as well as patterns of medication use, in individuals with HSD/EDS. this cross-sectional study included 37 participants diagnosed with HSD or EDS based on the 2017 Diagnostic Consensus Criteria. Participants were divided into two groups: 23 with SpA + EDS and 14 with EDS-only. Demographic variables, comorbidities, and medication use (biologics, disease-modifying antirheumatic drugs [DMARDs], and nonsteroidal anti-inflammatory drugs [NSAIDs]) were analyzed using comparative statistical methods. MCAS was significantly less prevalent in SpA + EDS participants (13%) compared to the EDS-only group (85.7%, p < 0.0001). POTS (60.9% vs 78.6%) and IBS (60.9% vs 85.7%) occurred at similar frequencies in both groups. The use of immunomodulators was higher in SpA + EDS (73.9%) than EDS-only (42.8%, p = 0.003). Biologic use was more common in SpA + EDS (34.8% vs 7.1%, p = 0.050), whereas NSAID use was higher in EDS-only participants (47.4% vs 30.4%, p > 0.05). the lower MCAS prevalence in SpA + EDS may reflect symptom overlap or suppression due to immunomodulatory treatments. Differences in medication use highlight variations in diagnostic and therapeutic strategies. Comprehensive evaluations are essential to ensure accurate diagnoses and optimal treatment approaches.

The combination of neurological, cardiac, and pulmonary disease in patients with systemic sclerosis (SS) is rare. The aim of the study was to report a patient with SS who manifested with migraine without aura, Raynaud's phenomenon, pulmonary hypertension, and postural tachycardia syndrome (POTS), a combination which has not been previously reported. The patient is a 53-year-old Caucasian woman with diffuse cutaneous SS who was treated with methotrexate and developed migraine without aura since the age of 6 years. Since age 31 years, she developed Raynaud's phenomenon with several attacks daily, which could be triggered by cold and also occurred in summer. At the age of 52 years, pulmonary fibrosis with secondary pulmonary hypertension was diagnosed and bosentan was administered. At the age of 53 years, POTS was diagnosed. The frequency of migraine was one per week at the age of 53 years. This case shows that migraine can be the initial manifestation of diffuse cutaneous SS, followed by Raynaud's syndrome, pulmonary hypertension and POTS.

Postural tachycardia syndrome (POTS) is a common, often disabling disorder of autonomic nervous system regulation without a unifying etiological account. Converging evidence suggests infectious, physical, and emotional threats frequently precede onset. We propose a hypothesis-generating model in which POTS may, in some individuals, involve threat-induced, centrally maintained disruption of brain-body communication that may be responsive to neuroplasticity-based behavioral medicine. In this paper, we synthesized multidisciplinary literature and our team's data spanning (a) autonomic and central nervous system responses to threat and trauma, (b) neurological alterations associated with early life stress, (c) links between adverse childhood experiences and posttraumatic stress disorder with autonomic symptom burden, and (d) clinical developments targeting the threat system and autonomic regulation. These data suggest that chronic or overwhelming threat exposure is associated with sympathetic activation, reduced vagal tone, and neuroplastic alterations within cortico-limbic and brainstem networks that parallel POTS features (exaggerated tachycardia, autonomic rigidity, multisystem dysregulation). Preliminary data indicate individuals with higher trauma exposure and PTSD symptoms report greater autonomic symptom severity and poorer global health. Emerging imaging suggests a potentially important role for the periaqueductal gray (PAG), a midbrain hub for autonomic, cardiovascular, motor, and pain responses to threat, which may fail to reset after trauma, leaving the ANS in a sustained escape-mode (fight/flight/freeze) that increases POTS risk. Overall, these findings provide preliminary conceptual support for a unified hypothesis linking trauma, PAG-mediated threat responses, and sustained autonomic dysregulation in POTS, underscoring the importance of trauma-informed care. Behavioral interventions that target threat reduction and autonomic regulation such as rate variability biofeedback and neuroplasticity-oriented psychotherapies, may complement standard medical care. Prospective, longitudinal studies are needed to clarify causal pathways and identify responsive subgroups, and randomized clinical trials are required to establish the efficacy of nervous system-focused behavioral interventions.

Background Ehlers-Danlos syndrome (EDS) encompasses a group of connective tissue disorders often extending beyond musculoskeletal involvement. Emerging evidence indicates a high prevalence of cardiovascular autonomic dysfunction in this population, yet systematic physiologic evaluations remain limited. Objective To characterize cardiovascular autonomic function in EDS using standardized autonomic testing and heart rate variability (HRV) indices, and to explore intrinsic autonomic coupling by correlating resting heart rate with HRV parameters. Methods This cross-sectional study included 30 clinically diagnosed patients with EDS and 30 age- and sex-matched healthy controls. Short-term HRV analysis (five-minute supine ECG) and standard autonomic testing, including head-up tilt, were performed under controlled laboratory conditions. HRV indices were derived using Fast Fourier Transform (FFT) algorithms. Group differences were evaluated with independent t-tests, and correlations between resting heart rate and HRV measures were analyzed using Pearson's correlation. Results Compared with controls, patients with EDS exhibited higher resting heart rate (87.3±11.6 vs 75.2±9.8 bpm), lower parasympathetic time-domain indices (standard deviation of normal-to-normal intervals or SDNN 35.4±9.7 vs 49.1±11.4 ms; root mean square of successive differences (RMSSD; 20.7±6.9 vs 31.6±8.8 ms), and altered frequency-domain markers (low frequency (LF) power 671±205 vs 542±176 ms²; high frequency (HF) power 174±81 vs 272±106 ms²; LF/HF ratio 3.7±1.3 vs 1.8±0.7). Orthostatic intolerance was observed in 16 (53.3%) of the patients with EDS versus three (10%) of the controls. Correlation analysis revealed that in EDS, resting HR correlated negatively with SDNN (r=-0.45, p=0.01), RMSSD (r=-0.52, p<0.01), and HF power (r=-0.39, p=0.03), while showing a positive correlation with LF/HF ratio (r=0.58, p<0.001). Conclusion Patients with EDS had autonomic dysregulation, with sympathetic predominance and diminished vagal modulation. The intrinsic coupling between resting heart rate and HRV indices suggests impaired cardiovascular autonomic integration. HRV profiling is a valuable noninvasive biomarker for early identification and longitudinal monitoring of autonomic dysfunction in EDS, potentially enhancing disease characterization and guiding individualized therapeutic strategies.

Postural orthostatic tachycardia syndrome (POTS) is defined as the presence of chronic symptoms of orthostatic intolerance accompanied by an increase in heart rate greater than 30 beats per minute within 10 min of assuming an upright posture in the absences of orthostatic hypotension. It is a condition which lacks a definitive treatment strategy, with weak evidence and clinical expertise to support the available guidelines from the Heart Rhythm Society in 2015 and the Canadian Cardiovascular Society in 2020. The limited systematic reviews evaluating the treatment for POTS only reported three or fewer trials when many more trials have been published. In this systematic review, we evaluate the evidence for different treatments for POTS from 21 randomized clinical trials with 750 patients that took place between 2000 and 2023. This review summarizes the available evidence from trials on propranolol, midodrine, pyridostigmine and ivabradine as well as less commonly used medications such as desmopressin, melatonin, atomoxetine, modafinil, sertraline and intravenous immunoglobulins. Moreover, the trial evidence for non-pharmacological treatments is described including increase intake of dietary sodium, exercise training, compression and devices. We conclude that many small trials have evaluated different treatments for POTS. Large randomized trials are needed to determine if mainstay treatments beta-blockers, midodrine, and pyridostigmine should be used as first line treatment(s).

Cardiovascular autonomic disorders (CAD) were described following COVID-19 infection and vaccination, but previous reports were limited in size and follow-up. Here, we aimed to investigate the type and frequency of newly diagnosed and exacerbated CAD following COVID-19 infection or vaccination, and assessed their associated autonomic and non-autonomic complaints, applied treatment, and clinical outcome at last follow-up. Medical records of individuals referred to the Innsbruck Dysautonomia Center between March 2020 and March 2023 were reviewed for new onset of orthostatic intolerance, recurrent syncope, OR exacerbation of previously diagnosed CAD within 6 weeks from a passed COVID-19 infection or vaccination. Following COVID-19 infection (n = 75), 22 (29%) individuals were diagnosed with postural orthostatic tachycardia syndrome (POTS), 12 (16%) with vasovagal syncope (VVS), 1 with delayed and 1 with transient orthostatic hypotension (OH). Following COVID-19 vaccination (n = 26), 11 (42%) POTS, 2 (8%) VVS, and 3 (12%) transient OH cases were newly diagnosed. In half of newly referred individuals (n = 49/101, 49%), the diagnostic workup excluded any CAD. VVS was the most frequently exacerbated CAD (n = 8/19, 42%). Non-pharmacological measures were recommended to all newly diagnosed CAD, with one-third additionally receiving pharmacotherapy. Follow-up was available in 42 (81%) individuals with newly diagnosed CAD, with a symptomatic improvement observed in 26 (62%) cases. A specialized diagnostic workup is pivotal to diagnose or exclude CAD in individuals with new-onset orthostatic intolerance or recurrent syncope following COVID-19 infection or vaccination. A multimodal treatment approach can achieve a symptomatic improvement in a substantial proportion of affected individuals.

Forms of dysautonomia, including Postural Orthostatic Tachycardia Syndrome (POTS), significantly impacts youth, yet psychosocial aspects remain under-researched, particularly outside of patients diagnosed with POTS. This study examines the clinical and psychosocial profiles of youth with autonomic dysfunction and compares findings between groups with different heart rate (HR) responses to orthostatic testing. This retrospective review analyzed demographics, symptoms, quality of life (QoL), and mental health variables (e.g., anxiety, depression, ADHD) in youth with autonomic dysfunction. Differences between higher and lower HR response groups were compared. QoL was assessed using the PedsQL™ and symptom severity was measured with the Malmö POTS Symptom Score (MAPS). Medical history and psychosocial concerns were extracted from electronic medical records. Symptom severity scores exceeded clinical cutoffs for the full sample (65.8) and across HR groups. Independent t-tests showed no differences between groups for any variable. Pain (92.5 %) and impaired eating (42.5 %) were prevalent across the sample. QoL was clinically impaired in all domains, and mental health concerns, such as anxiety (83.3 %) and depression (54.3 %), were common. Findings describe the pervasive symptom and psychosocial burden in youth with autonomic dysfunction, which was consistent across higher and lower HR response groups. The study emphasizes the importance of addressing medical, mental health, and daily life challenges in all patients seen for autonomic dysfunction. Additionally, it highlights the importance of expanding research and clinical focus to include all youth with autonomic dysfunction, regardless of HR response to ensure youth who are experiencing impairment obtain the comprehensive care they need.

Cardioneuroablation (CNA) is increasingly used worldwide in the treatment of functional bradyarrhythmia mediated by excessive vagal tone. However, a potential early or long-term complication is the development of postprocedural inappropriate sinus tachycardia (IST), which remains difficult to manage. Recent data suggest that sinus node (SN)-sparing hybrid ablation may offer promising long-term outcomes in patients with IST and postural orthostatic tachycardia syndrome (POTS). We present what is, to our knowledge, the first documented case of such a procedure performed for IST/POTS following an uncomplicated CNA for symptomatic vagally mediated sinus bradycardia (SB). The comprehensive treatment strategy included on-site cardiac rehabilitation, a home-based telerehabilitation program, and evaluation using cardiovascular autonomic functional testing (CAFT) and the Malmö POTS scoring system. We present a 33-year-old woman with a 6-month history of dizziness, palpitations, exercise and orthostatic intolerance, dyspnea, presyncope, and one syncope episode. Symptoms of IST (130-170 bpm) appeared within 1 week after CNA for symptomatic SB. Despite the diagnosis of IST, CAFT have confirmed POTS. Other causes of sinus tachycardia (ST) were excluded according to guidelines. Nonpharmacological and pharmacological treatment proved ineffective. Following shared decision-making, the patient was referred for SN-sparing hybrid ablation with right-sided video-assisted thoracoscopic surgery (VATS). The patient subsequently participated in hybrid cardiac rehabilitation. At the 3-month follow-up, she was drug free and maintained a normal sinus rhythm. No evidence of bradycardia, IST/POTS, or vasovagal syncope (VVS), including CAFT, was documented during the follow-up. The serial MALMO POTS scoring system before and 3, 6, 9, 12 and 18 months after SN-sparing hybrid ablation demonstrated consistent and significant improvement, with scores decreasing from 46 to 13, 10, 6 and 12 points, respectively, values comparable to those observed in the healthy population. This is the first reported case of SN-sparing hybrid ablation for IST/POTS that developed after primary, uncomplicated CNA. Although not yet included in guidelines, the implementation of both procedures for cardiovascular autonomic dysfunction (CVAD) requires comprehensive and multidisciplinary heart team management. The MALMO POTS scoring system might be a useful tool for assessing CVAD before and after cardioneuromodulation procedures and further comprehensive evaluation.