Postural orthostatic tachycardia syndrome (POTS) is widely treated as a cardiovascular-autonomic syndrome, but cognitive dysfunction is a disabling and poorly treated clinical phenomenon. This scoping review discusses why brain fog, impaired attention, slowed processing speed, memory difficulties, word-finding issues, and executive dysfunction may persist despite conventional pharmacological and non-pharmacological POTS treatments. The study uses a structured scoping review design to synthesize 18 peer-reviewed sources that meet the inclusion criteria, with publication dates between 2013 and 2025, across the domains of mechanistic, clinical, treatment, rehabilitation, and interventional studies. The evidence can be grouped into three principal mechanistic pathways: cerebral hypoperfusion and hemodynamic dysfunction; autonomic dysregulation and sympathetic overactivation; and neuroinflammation, autoimmune responses, mast cell activation, and microclot formation. The review found that abnormal cerebral blood flow (CBF) was reported in 61% of 56 POTS patients with cognitive dysfunction, and that sustained cognitive stress induced a greater reduction in CBF velocity in POTS patients than in controls, at approximately 7.8% and 1.8%, respectively. Current therapies, including beta-blockers, ivabradine, midodrine, exercise, salt and fluid loading, compression garments, cognitive behavioral therapy (CBT), and sleep management, rarely use cognition as a primary endpoint. Findings suggest that persistent cognitive dysfunction in POTS may reflect incomplete alignment between neurological mechanisms and cardiovascular-centered care, requiring validated cognitive outcomes and multimodal trials combining biological, autonomic, and rehabilitative interventions.

Postural orthostatic tachycardia syndrome (POTS) is associated with autonomic dysregulation, but ambulatory markers that capture autonomic phenotype remain incompletely defined. To compare Holter-derived heart rate variability (HRV) metrics between adolescents with POTS and healthy controls and to derive candidate discriminatory thresholds. Retrospective case-control analysis of an existing Holter dataset (POTS n = 19, controls n = 44). Heart rate variability was processed in Kubios HRV Premium. Between-group comparisons used Welch's t-test with Benjamini-Hochberg false discovery rate adjustment. Nonparametric sensitivity analyses yielded similar results. Discrimination was assessed using receiver operating characteristic analysis; optimal thresholds were defined by the Youden index. An exploratory penalized logistic regression model (L1 regularization) was fit with standardized candidate HRV predictors and internal cross-validation. Among 19 POTS patients and 44 control subjects, POTS demonstrated lower time- and frequency-based HRV, higher rate-related and sympathetic composite indices, and lower parasympathetic composite measures. The strongest univariate discriminator was PNSi (Parasympathetic Nervous System index; AUROC 0.874; threshold ≤ -1.10; sensitivity 77.8%; specificity 88.6%). Other high-performing discriminators included SNSi, mean RR, mean heart rate, and SDNNi. Holter-derived HRV metrics demonstrate a reproducible pattern consistent with reduced parasympathetic modulation and relative sympathetic predominance in POTS. Several variables yield candidate discriminatory thresholds that may support physiologic phenotyping and warrant validation in independent cohorts.

Postural orthostatic tachycardia syndrome (POTS) is a disorder characterized by a sudden onset of orthostatic intolerance upon standing, which may be relieved when lying down. The most common complications associated with POTS are trauma or injury from falling or fainting. Pediatric patients with POTS may have comorbidities that interfere with their quality of life. Careful management of the disorder is essential to prevent injury. POTS management is often misunderstood, which may lead to misdiagnosis and invalidation by health care professionals. This article discusses how POTS affects pediatric patients and the implications for nursing practice.

Functional disorders affecting the cardiorespiratory system are common. Non-cardiac chest pain affects more than 10% of the population. It can result from gastro-oesophageal reflux or chest wall disorders but is also very often associated with anxiodepressive disorders, particularly panic disorder. Postural orthostatic tachycardia syndrome (POTS), a rarer entity, is characterized by a sharp increase in heart rate without orthostatic hypotension when standing. The pathophysiological mechanisms of POTS include 'partial' autonomic neuropathy, hypovolaemia and noradrenergic dysregulation, but it is also closely linked to anxiety disorders and deconditioning to exertion. Functional respiratory disorders, particularly hyperventilation syndrome, are accompanied by various manifestations ranging from tetany to gastrointestinal symptoms. They are highly prevalent, especially among women and people suffering from anxiety, and particularly in the case of associated respiratory disease such as asthma. The diagnosis of hyperventilation syndrome is based on the Nijmegen questionnaire. The pathophysiology does not necessarily involve hypocapnia but is related to cerebral conditioning phenomena and vicious circles linked to anticipatory anxiety. Cardiorespiratory functional disorders are often linked to each other and to other functional somatic disorders and have in common a dysregulation of the autonomic nervous system. Psychological, cognitive and behavioural factors play a central role in their persistence. While each has its specificities, all have a complex circular causality. Their management currently relies primarily on physical rehabilitation, often associated with symptomatic treatments such as beta-blockers. The place of cognitive and behavioral therapies would be well worth exploring in these disorders.

Long COVID-19 is recognized as a condition associated with autonomic nervous system (ANS) dysfunction. However, quantitative evidence of its impact on heart rate variability (HRV) and blood pressure (BP) regulation during postural changes remains limited. This study assessed autonomic imbalance in post-COVID-19 patients by evaluating HRV and BP responses during tilt table testing, comparing long COVID-19 patients with healthy controls. A total of 61 participants were enrolled, 39 long COVID-19 patients (Study Group, SG) and 22 healthy controls (Control Group, CG). HRV was analyzed using time- and frequency-domain parameters. BP monitoring evaluated systolic, and diastolic blood pressure (SBP, and DBP respectively), and Pulse pressure (PP = SBP-DBP) was calculated for each phase. SG participants exhibited marked autonomic dysfunction during tilt. In the upright phase, they showed a significant increase in mean RR intervals (p = 0.0136), reduced normalized low-frequency (LF) with p = 0.0316, increased normalized high-frequency (HF) with p = 0.0315, and a decreased low-frequency/high-frequency (LF/HF) ratio (p = 0.0316), indicating a blunted sympathetic response and impaired autonomic adaptation to orthostatic stress. BP responses were also impaired: SG demonstrated attenuated changes in PP (ΔPP) when transitioning from the upright position to the recovery phase (p < 0.037). Within-group analysis confirmed persistent RR interval instability (p < 0.0001), incomplete normalization of LF and HF components (both p < 0.0001), and delayed recovery of PP after return to supine position. BP responses were also diminished: SG showed smaller ΔPP when moving from standing upright to the recovery phase (p < 0.037). Baroreflex sensitivity values did not differ between groups. Long COVID-19 patients display significant autonomic dysregulation, characterized by reduced HRV, abnormal BP responses. These findings highlight the value of tilt testing in uncovering hidden dysautonomia and support the need for targeted interventions, including pharmacologic modulation and long-term HRV/BP monitoring, to improve cardiovascular stability in long COVID-19.

Postural orthostatic tachycardia syndrome (POTS) is a multifactorial disorder of the autonomic nervous system characterised by an excessive increase in heart rate (HR) on standing and a wide range of debilitating symptoms, including fatigue, exercise intolerance, cognitive impairment and a high prevalence of depression, anxiety and sleep disturbances. Conventional pharmacological strategies often offer limited relief and do not sufficiently address non-cardiac symptoms. Auricular vagal neuromodulation therapy (AVNT) and slow-paced diaphragmatic breathing (SDB) have each demonstrated promise in modulating autonomic function and alleviating symptom burden but their combined effects in POTS have yet to be investigated. This single-centre, partially blinded, 12-week randomised controlled trial will be conducted at the Medical University of Vienna. A total of 100 participants with confirmed POTS will be recruited, with 25 per group. This sample size is already accounting for an anticipated 30% dropout rate. Participants will be randomised using stratified block randomisation with a 1:1:1:1 allocation ratio, stratified based on the presence or absence of post-exertional malaise (yes/no) to one of four groups: (1) AVNT+SDB, (2) AVNT+normal breathing, (3) sham AVNT+SDB and (4) sham AVNT+normal breathing. The primary endpoint is the change in orthostatic HR (ΔHR) during a 70° head-up tilt test. Secondary outcomes include beat-to-beat blood pressure responses, respiratory sinus arrhythmia, end-tidal CO₂, handgrip strength, activity monitoring and validated patient-reported measures, including Chalder Fatigue Scale, Malmö POTS Symptom Score, Nijmegen Questionnaire, Short Form Health Survey, Hospital Anxiety and Depression Scale and Vanderbilt Orthostatic Symptom Score. Interventions consist of daily 60-minute AVNT (or sham) sessions combined with standardised breathing training (10-15 min/day). This study has been approved by the Ethics Committee of the Medical University of Vienna (EK number 1270/2024) and will be conducted in accordance with the Declaration of Helsinki and International Conference on Harmonisation-Good Clinical Practice guidelines. Results will be disseminated through peer-reviewed publications, conference presentations and reporting in the trial registry. Participants will receive study results in an accessible format. NCT06996314.

Superior mesenteric artery (SMA) syndrome is a rare cause of proximal intestinal obstruction resulting from compression of the third portion of the duodenum between the aorta and the SMA. It most commonly occurs in slender individuals or those experiencing rapid weight loss, but presentations can be atypical and diagnostically challenging. We report the case of a 28-year-old female with history of postural orthostatic tachycardia syndrome and gastroparesis who presented with recurrent nausea and intractable vomiting following a 110-lb weight loss after prior obesity. Upper gastrointestinal endoscopy and gallbladder ultrasonography were unremarkable. Computed tomography of the abdomen demonstrated findings consistent with SMA syndrome, including severe narrowing of the aortomesenteric angle and reduced aortomesenteric distance. The patient subsequently underwent robotic-assisted duodenojejunostomy with resolution of symptoms. This case highlights an atypical presentation of SMA syndrome following massive weight loss and demonstrates the feasibility of robotic duodenojejunostomy as an effective treatment option.

Establishing evidence of vaccine safety is critical for optimizing vaccine coverage. This study aimed to assess the risk of developing neurological disorders following human papillomavirus (HPV) vaccination. This retrospective cohort study compared the risk of developing neurological disorders between HPV-vaccinated and unvaccinated cohorts using the TriNetX platform. Outcomes included complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), polyneuropathies, dysautonomia, Guillain-Barré syndrome (GBS), encephalitis, myelitis or optic neuritis, Bell's palsy, epilepsy, narcolepsy, and intracranial injury (negative control outcome). The hazard ratios (HRs) were estimated by propensity score matching. In the USA, following propensity score matching, 715,540 participants from each cohort were matched. The HRs were not increased following vaccination for any of the investigated outcomes, including CRPS, POTS, polyneuropathies, dysautonomia, GBS, encephalitis, myelitis or optic neuritis, Bell's palsy, epilepsy and narcolepsy. No increased risk of the selected neurological adverse events was observed in the vaccinated group. The data should be interpreted with caution given potential residual confounders and a possibility that high-risk population with neurological conditions were less likely to receive the vaccination. This study contributes to the establishment of evidence for the safety of HPV vaccines.

Postural orthostatic tachycardia syndrome (POTS) is a chronic autonomic disorder characterized by an excessive increase in heart rate upon standing, accompanied by symptoms such as dizziness, fatigue, palpitations, cognitive impairment, and sleep disturbances. Sleep dysfunction is increasingly recognized as a significant contributor to symptom burden and reduced quality of life among individuals with POTS. Emerging evidence suggests that patients with POTS may experience heightened sympathetic activity during sleep, leading to disrupted autonomic regulation and fragmented sleep patterns. While the pathophysiological mechanisms underlying sleep disturbances in POTS are multifactorial, modifiable lifestyle factors - including dietary habits and environmental exposures - may play an underexplored role. Dietary factors such as high-fat meals or specific dietary patterns may influence sleep architecture and nocturnal awakenings, whereas interventions such as gluten-free diets have shown potential benefits in alleviating certain gastrointestinal and vasomotor symptoms associated with POTS. Environmental determinants, including chronic noise exposure and light pollution, can further disrupt circadian rhythms by impairing melatonin secretion and altering sleep quality. These disruptions may exacerbate autonomic imbalance, perpetuating daytime symptoms such as tachycardia and fatigue. Despite plausible mechanistic links, targeted research examining the influence of diet and environmental factors on sleep quality in POTS remains limited. Addressing these modifiable factors may provide novel lifestyle-based strategies to complement pharmacological management and improve patient outcomes.

This review provides an overview of POTS in children and adolescents with headaches, with a focus on the pharmacologic and non-pharmacologic treatment approaches. Current research in headache and POTS focuses on an individualized management that includes a multi-tiered patient-centric approach that selects treatments to match specific phenotypes. The management of pediatric POTS and headache requires the individualized characterization of a patient's phenotype, an assessment of an individual's contributing lifestyle factors, the use of non-pharmacologic interventions, and the consideration of pharmacologic options.

Postural orthostatic tachycardia syndrome (POTS) as conventionally defined is a chronic condition (typically > 3 months duration) incorporating reproducible symptoms of orthostatic intolerance (including dizziness/lightheadedness, and near-syncope) in the absence of orthostatic hypotension (ie, absence of a sustained systolic blood pressure drop > 20mmHg with upright posture). More recently, however, the :POTS: landscape as applied by many clinicians has broadened; the term :POTS: has become increasingly used to categorize a multisystem disorder the underlying etiologies of which remain unclear but may include autonomic dysfunction and/or autoimmune disorders; as such the clinical picture has evolved to encompass a wide range of non-cardiovascular symptoms such as persistent exertional intolerance, fatigue, "brain fog", thermo-regulatory disorders, and various gastrointestinal symptoms including gastroparesis and certain food intolerance reactions. Thus, while cardiovascular disorders may be the principal manifestation of presumed "POTS" in many patients, disturbances in a variety of body systems may dominate the clinical presentation in others. This communication, derived from a diverse group of practitioners who care for the wide range of patients often referred for :suspected POTS:, offer the view that optimizing diagnostic evaluation and subsequent care of these individuals necessitates a broad range of clinical skills; in essence involvement of a "village" of dedicated multi-talented care providers.

Postural orthostatic tachycardia syndrome (POTS) is increasingly recognized after SARS-CoV-2 infection. We compared autonomic phenotype, functional impact, and circulating immune markers in POTS, postacute sequelae of COVID-19 (PASC), and healthy controls. In this cross-sectional study (August 2021 to December 2022), we recruited patients with POTS (n=24) or PASC (n=24) and healthy controls (n=19). Participants underwent 10-minute active stand testing, 24-hour Holter monitoring, serum cytokine, and adrenergic autoantibody assays (cell-based activation). Patient-reported outcome measures were collected via secure electronic link. The study included 67 participants (mean age, 32.4±8.9 years; 71% women). Compared with controls and participants with PASC, participants with POTS demonstrated significantly higher orthostatic tachycardia (active stand heart rate change from supine to standing, 46.3±14.0 bpm versus 12.7±6.6 bpm in controls and 34.6±13.7 bpm in PASC; <0.001; POTS versus PASC =0.005). Among participants with PASC, 62.5% met formal POTS criteria. Cytokine analysis revealed lower interleukin-2 and higher interleukin-8 levels in POTS versus controls, with POTS cases showing elevated tumor necrosis factor-α compared with those without POTS. Autoantibody activation measures did not differ significantly among groups, and multivariate biomarker models lacked predictive utility for POTS diagnosis. Patient-reported outcome measures indicated greater fatigue, orthostatic intolerance, and autonomic symptom burden and reduced health-related quality of life in POTS and PASC groups compared with controls. POTS and PASC exhibit overlapping autonomic symptomology and profound functional impairment. Alterations in cytokines suggest a possible cytokine-linked or compartmentalized immune contribution, but cytokine and autoantibody measures alone do not predict POTS. Routine autonomic assessment in persistent postviral illness and larger longitudinal, multimodal studies are warranted. Australian New Zealand Clinical Trial Registry; ACTRN: 12621000476831.

Gastric electrical stimulation (GES) improves refractory nausea and vomiting in children, but the impact on non-gastrointestinal symptoms remains unclear. We identified patients < 21 years old treated with GES between 2016 and 2024. Patients completed the Symptom Monitor Worksheet (SMW), Pediatric Quality of Life Inventory (PedsQL), and Children's Somatic Symptoms Inventory (CSSI) at baseline before GES and at 14 days, 2, 6, and 12 months follow-up. We used a linear mixed effects regression model and a random intercept for each subject to capture individual variability in assessment of score changes during the first year and to evaluate differences in CSSI based on symptom response defined as > 1 point improvement in average SMW score from baseline to last follow-up. We included 34 patients (79% female, mean age 15.4 years): 97% had gastroparesis, 50% functional dyspepsia, 47% postural orthostatic tachycardia syndrome, and 67% a history of anxiety/depression. After 1 year of GES treatment, there was sustained improvement in SMW and PedsQL. CSSI improved over the first 6 months and remained improved numerically at the end of the year, but this was not statistically significant. Sixteen patients met criteria for greater response and 18 for lesser response based on degree of SMW improvement. Baseline CSSI, including GI and non-GI subsets, was similar between patients with greater and lesser response to GES, and both experienced transient improvement in the non-GI somatic symptoms. Children treated with GES experienced sustained improvement in GI symptoms and quality of life, but only transient improvement in non-GI somatic symptoms.

Cerebral venous outflow disorders (CVD) are conditions characterized by impairment of cerebral venous drainage. Associated symptoms have been poorly defined, as no standardized diagnostic criteria exist for this class of conditions; most studies to date have attempted to report on symptoms solely based on suggestive noninvasive imaging findings, which is prone to selection bias. The aim of this study was to characterize symptoms that may be present in the setting of suspected internal jugular vein outflow stenosis. A survey was conducted among patients with suspected CVD who had previously undergone diagnostic dynamic cerebral venography and subsequent internal jugular vein stenting or styloidectomy from 2019 to 2025. Following distribution to 133 patients, 60 (45.1%) responded. Fifty (83.3%) of the 60 respondents indicated an improvement in symptoms following intervention. Brain fog (49, 98.0%), headache (48, 96.0%), and fatigue/low energy (46, 92.0%) were the most frequently reported symptoms pre-procedure. Uncontrollable seizures or shaking spells, headache, and eye pain were the most responsive to intervention, with improvement rates of 87.5%, 81.3%, and 81.0%, respectively. Nineteen of 50 respondents endorsed a diagnosis of Postural Orthostatic Tachycardia Syndrome; 8 of 19 reported improvement in Postural Orthostatic Tachycardia Syndrome symptoms after their procedure. There is a wide range of symptoms that may be present in patients with CVD. This survey illustrates the most common complaints among suspected patients with CVD and elicits which symptoms are likely due to cerebral venous outflow impairment, based on responsiveness to intervention.

Pediatric postural orthostatic tachycardia syndrome is one of the main haemodynamic types of neurally mediated syncope and is commonly seen in school-aged children. Heart rate and blood pressure are important physiological indicators in the human cardiovascular system. They are easily accessible in clinical practice and have the advantages of being non-invasive, simple and safe. This article will review the predictive value of heart rate and blood pressure in the diagnosis and prognosis of pediatric postural orthostatic tachycardia syndrome.

Compression garments are a relatively inexpensive and easy-to-implement treatment, but the longer term benefits of abdominal compression in a real-world setting are not known. In this study we sought to evaluate commercially available abdominal compression garments in a real-world setting in patients with postural orthostatic tachycardia syndrome (POTS). Participants completed four 10-minute active stand tests, with and without an abdominal compression garment, in the morning (Test #1: AM-OFF; Test #2: AM-ON) and afternoon (Test #3: PM-ON; Test #4: PM-OFF). Participants held medication that could augment heart rate (HR) and blood pressure during this 1-day study. A Holter monitor was used to record HR and participants recorded their symptoms using the Vanderbilt Orthostatic Symptom Score at the end of each standing test (range 0-90, where 0 = no symptoms). Continuous data are presented as median (25th-75th percentile). Standing HR (103 [91-114] vs 118 [99-134], P = 0.002) and change in HR with upright posture compared with supine (27 [19-42] vs 41 [26-48], P < 0.001) were reduced, and symptoms improved (29 [16-45] vs 35 [25-60], P = 0.005), during AM-ON compared with AM-OFF. When the garment was removed after several hours of use (PM-ON vs PM-OFF), standing HR (P = 0.04), ΔHR (P = 0.01), and symptoms (P = 0.02) increased. Commercially available abdominal compression garments reduced HR and improved symptoms both acutely and after several hours of use. Abdominal compression garments may provide a good alternative to full waist-high compression garments in patients with POTS. NCT04881318.

Ivabradine is one of several off-label treatments for patients with postural orthostatic tachycardia syndrome (POTS). We conducted a systematic review of the literature to identify studies that evaluate ivabradine treatment in patients with POTS. The results were narratively synthesized given methodological heterogeneity among the identified studies. There were 11 studies included in the analysis with 305 participants between 2008 and 2020. The only randomized trial of 22 patients showed that ivabradine improved heart rate compared with placebo, and there were symptomatic benefits in terms of physical functioning and social functioning. All studies suggested a reduction in heart rate with ivabradine treatment; the proportion of patients with symptomatic benefit ranged from 67% to 100%. One study using the Malmo POTS score found that ivabradine improved the total score, including key components such as light-headedness with standing, feeling faint, feeling rapid heart rate, and chest pain. Although 2 studies did not report side effects and 2 studies described no side effects, others reported adverse effects including bradycardia, nausea, worsening syncope, palpitations, flushing, light sensitivity, headache, light-headedness, fatigue, scalded tongue, itching and burning, and visual disturbance. In conclusion, there is low-quality evidence derived from small observational studies and 1 small randomized trial that ivabradine is effective in reducing heart rate and improving symptoms in patients with POTS. The exact role of ivabradine in treatment of POTS needs to be clarified in further randomized trials and more robust evidence.

To compare Functional Disability Inventory (FDI) between adolescents with chronic orthostatic intolerance (COI) and postural orthostatic tachycardia syndrome (POTS). This cross-sectional study included adolescents ≤19 years with orthostatic symptoms >3 months referred to a tertiary pediatric autonomic clinic (August 2024-March 2025) and classified as POTS or COI based upon active stand testing. Self- and parent-reported FDI scores were collected. Group comparisons used chi-square and Wilcoxon-Mann-Whitney tests. Univariable and multivariable linear regression models compared FDI scores, adjusting for age, sex, and body mass index. Adjusted means were estimated using post-fit marginal estimation. Ninety-two adolescents were included (46 POTS, 46 COI). Groups were similar in age, sex, and body mass index, but differed in heart rate response by definition. Self-reported FDI scores did not differ between COI and POTS in unadjusted (22.9 vs 22.4; P = .81) or adjusted analyses (adjusted mean difference 1.0, 95% CI -3.0 to 4.9; P = .63). Parent-reported FDI scores were also comparable in unadjusted (23.1 vs 22.3; P = .70) and adjusted analyses (adjusted mean difference 0.4, 95% CI -3.4 to 4.2; P = .85). Differences were well below the prespecified threshold for clinical significance. There was no evidence for a difference in functional disability in adolescents with COI, regardless of tachycardia-based POTS classification. This suggests that heart rate response is not associated with functional differences in pediatric orthostatic intolerance.

Post‑acute sequelae of SARS‑CoV‑2 infection (Long COVID) affect a substantial proportion of individuals, and among the many reported symptom clusters, autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), represents an important subset. The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative developed by the National Institutes of Health included a platform trial (RECOVER-AUTONOMIC) designed to assess the safety, tolerability, and efficacy of 3 interventions-(1) coordinated nonpharmacologic care, (2) pharmacotherapy with intravenous immunoglobulin (IVIG), and (3) pharmacotherapy with ivabradine-in treating POTS in adults with Long COVID. RECOVER-AUTONOMIC is a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. Participants are randomized to IVIG or ivabradine with matching placebo, and (in a factorial design) to either coordinated nonpharmacologic care or usual care. The primary endpoint is the change in orthostatic intolerance symptoms measured by the Orthostatic Hypotension Questionnaire/Orthostatic Intolerance Questionnaire from baseline to the end of intervention. Secondary endpoints include quality of life, functional performance, symptom burden, and safety. Exploratory endpoints include autonomic function testing, wearable sensor data, and longitudinal biomarker profiling. RECOVER-AUTONOMIC seeks to determine the benefits and risks of IVIG and of ivabradine, as well as of coordinated nonpharmacologic care, for the treatment of POTS in Long COVID. Results from this trial will offer the largest source of evidence to help guide the medical care of this population. ClinicalTrials.gov-Platform: NCT06305780; Appendix A (intravenous immunoglobulin): NCT06305793; Appendix B (ivabradine): NCT06305806. Protocol available at https://trials.recovercovid.org/autonomic.

Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder characterized by orthostatic intolerance and excessive tachycardia upon standing. Despite its prevalence, POTS is often underdiagnosed or diagnosed late, largely due to limited access to autonomic specialists and testing. This study aimed to evaluate the performance of machine learning (ML) models in diagnosing POTS using validated symptom surveys and physiological measurements. We retrospectively analyzed data from patients evaluated at the Autonomic Laboratory at Brigham and Women's Faulkner Hospital (2017-2025), with POTS diagnoses confirmed by autonomic testing. ML models based on a multilayer perceptron were trained using patient-reported surveys (Survey of Autonomic Symptoms [SAS], COMPASS-31) and autonomic testing data. Importantly, no orthostatic heart rate criteria for the POTS diagnosis were provided to the models. A total of 3210 patients were included, of whom 810 had confirmed POTS. All patients completed SAS; 1337 also completed COMPASS-31 (334 with POTS). Models incorporating heart rate data achieved the highest diagnostic accuracy (PyTorch/LightGBM: AUC 0.98/0.99; precision 0.94/0.93; F1 score 0.88/0.93; sensitivity 83%/92%; specificity 98%/98%). In contrast, models trained solely on SAS (AUC 0.68/0.63) or COMPASS-31 (AUC 0.66/0.62) performed poorly. ML models accurately diagnosed POTS when incorporating heart rate data alongside survey responses, with heart rate data being the strongest predictor. These findings suggest ML could assist in POTS diagnosis. The study also highlights the importance of heart rate measures in POTS diagnosis.

Disorders of gut-brain interaction (DGBI) affect about 40% of children and are often comorbid with hypermobility spectrum disorders (HSDs) and orthostatic intolerance (OI). However, how these comorbidities impact outcomes in pediatric DGBI is not well understood. This study aimed to compare outcomes in DGBI patients with HSD, OI, both, or neither. We reviewed records of patients aged 9-21 years from a multidisciplinary DGBI clinic. Patients met Rome IV criteria for DGBI and had documented HSD and/or OI diagnoses from specialists in gastroenterology, rheumatology, genetics, cardiology, adolescent medicine, and others. HSD terms included Ehlers-Danlos syndrome, hypermobile Ehlers-Danlos syndrome, and generalized hypermobility; OI terms included postural orthostatic tachycardia syndrome, dysautonomia, and orthostatic hypotension. Clinical data included the following validated questionnaires: abdominal pain index, nausea severity scale, functional disability inventory, patient health questionnaire-9 (Depression), children somatization inventory, pediatric insomnia severity index, pain catastrophizing scale for children, and screen for child anxiety related disorders (Anxiety). We compared DGBI patients with both HSD and OI, those with either disorder, and those without. Of 175 patients, 46% had HSD and 43% had OI. Patients with both HSD and OI had significantly worse nausea, depression, disability, and somatization scores than others (p < 0.01). HSD and OI groups individually also showed worse outcomes than non-HSD/non-OI groups. Moderate correlations were found between depression and anxiety in OI and nausea and disability in HSD. Comorbid HSD and OI worsen DGBI symptoms. Accurate diagnosis and treatment are critical to improving outcomes due to shared autonomic dysfunction.

Postural orthostatic tachycardia syndrome (POTS) represents a growing clinical and public health challenge, particularly in the context of post-infectious and post-COVID-19 syndromes. Recent systematic synthesis highlights that, despite widespread clinical use of pharmacologic and non-pharmacologic interventions, high-certainty randomized evidence remains scarce and heterogeneous. In this correspondence, prompted by contemporary treatment reviews, we argue that the primary limitation is no longer the absence of therapies but the absence of decision-grade trial architecture. We propose an audit-ready, globally scalable framework that integrates phenotype-stratified pragmatic trials, platform-based comparative effectiveness designs, and a minimum core outcome set anchored to minimally clinically important differences. Emphasis is placed on patient-relevant functional recovery, interpretability across health systems, and equitable implementation beyond tertiary autonomic centers.

To support general neurologists, advanced practice providers, and general practitioners in the diagnosis and treatment of postural tachycardia syndrome (POTS) and related dysautonomias. This review and approach are based on the authors' clinical experience, nonsystematic literature review, and expert opinion, with experts drawn from the American Autonomic Society Education Committee. POTS is a common condition seen in general practice. The diagnosis can be easily made in a nonspecialist setting when patients meet the syndromic criteria for POTS: (1) chronic orthostatic intolerance (bothersome symptoms brought on by upright posture, and relieved by lying down), (2) excessive orthostatic tachycardia (heart rate augmentation with standing greater than 30 beats per minute in adults), (3) absence of orthostatic hypotension, and (4) reasonable exclusion of other causes (e.g., dehydration, anemia, hyperthyroidism). There are many causes, but the unifying perturbations are low effective circulating volume with decreased cerebral blood flow and a hypersympathetic state. Education and nonpharmacologic therapies such as salt, water, and exercise are first-line treatments. Several safe and effective medication options are also available, such as propranolol and midodrine. Several comorbidities are common, such as migraine and neurocardiogenic syncope, and should be screened for and treated rather than attributed out-of-hand to POTS. POTS and related conditions are common. Initial diagnostic and treatment steps can be undertaken in a general practice setting. Referral to specialists is appropriate for refractory cases or when the diagnosis is uncertain.