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.

Postural orthostatic tachycardia syndrome (POTS) is widely described as a chronic disorder of cardiovascular autonomic regulation, characterized by an exaggerated increase in heart rate upon standing [1]. The condition disproportionately affects women of reproductive age [2]. However, the clinical manifestations of POTS extend far beyond the cardiovascular system. Patients frequently experience a broad spectrum of symptoms, including exercise intolerance, cognitive difficulties such as impaired memory and concentration, gastrointestinal disturbances, and sleep disruption—often as prominently as palpitations and orthostatic intolerance [3]. Despite its substantial impact on quality of life, the long-term trajectory of POTS remains uncertain: Is it a lifelong condition or one from which patients may recover spontaneously?

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.

Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by an excessive increase in heart rate upon standing, in the absence of orthostatic hypotension. Post-infectious forms, particularly following SARS-CoV-2 infection, have been increasingly reported. We report the case of a 34-year-old woman presenting with persistent palpitations, marked fatigue, and orthostatic intolerance that developed two weeks after a mild COVID-19 infection. Standard cardiological evaluation revealed no abnormalities. Comprehensive autonomic testing demonstrated an increase in heart rate from 72 to 109 beats per minute at the 11th minute of active standing (Δ +37 bpm), without significant blood pressure drop, confirming the diagnosis of POTS. Additional autonomic assessment identified a hyperadrenergic phenotype. After two months of treatment with ivabradine (5mg daily), heart rate in the standing position stabilized between 80 and 100 beats per minute, with partial clinical improvement. This case highlights the importance of comprehensive autonomic evaluation in post-COVID forms of POTS and supports the role of targeted therapy.

Long COVID Postural Orthostatic Tachycardia Syndrome (LCPOTS) is characterized by persistent orthostatic tachycardia and systemic symptoms following SARS-CoV-2 infection. Many features of LCPOTS suggest ongoing immune activation, but the mechanisms driving this response remain unclear. In this study, we show that patients with LCPOTS, compared with individuals who recovered from SARS-CoV-2 without POTS, exhibit increased monocyte mitochondrial content and superoxide production, along with downregulation of NRF2-dependent antioxidant enzymes. This is accompanied by a marked increase in the formation of isolevuglandins (IsoLGs) in monocytes, which modify self-proteins and act as neoantigens capable of activating T cells. Consistent with this, LCPOTS patients exhibit a 3-fold increase in circulating T cell-monocyte doublets with immunological synapse formation. T cells in these complexes display a proinflammatory effector-memory and TEMRA phenotype, producing IFN-γ and IL-17A, which correlated with symptom severity. Circulating cytokines, including IL-17A, IFN-γ, and TNF-α, are elevated in patients with LCPOTS by 1.5 to 3-fold. This immune response likely drives systemic inflammation and impaired cardiovagal regulation, hallmarks of LCPOTS. Our findings suggest that monocyte oxidative stress and IsoLG neoantigen formation sustain T cell activation, linking immune dysregulation to cardiovagal dysfunction. Targeting these pathways may offer novel therapeutic opportunities.

This report is an assessment of the characteristics associated with cardiovascular dysautonomia (CVD) in the context of long Coronavirus disease (COVID), which is currently inadequately characterized. A retrospective cross-sectional study was performed involving 106 patients with long COVID, including 34 individuals diagnosed with CVD, among whom eight met the criteria for Postural Tachycardia Syndrome (PoTS). The variables assessed encompassed individual characteristics (e.g., age, sex, comorbidities), immunization parameters (e.g., vaccination/viral status, timing, frequency), cellular and humoral anti-Spike and anti-Nucleocapsid (Nuc) immune responses, inflammatory and allergic biomarkers, as well as an extensive panel of common autoantibodies comprising anti-nuclear antibodies, anti-central nervous system antibodies (cerebellum, brain), and anti-peripheral nervous system antibodies (gangliosides). An age < 45 years, body mass index, hyperventilation syndrome as well as a higher cumulative number of antigenic contacts (vaccinations plus infections ≥ 3) and an elevated basophil count (≥0.06 G/L) were independently associated with CVD. There was no association between CVD and inflammatory markers or common autoantibodies. Patients with PoTS criteria had a strong anti-Spike cellular immune response and increased IgG anti-Nuc humoral immunity when compared with CVD and non-CVD long COVID counterparts. Compared to other long COVID patients, patients with long COVID-associated CVD have distinctive clinical and immunovirological features. Our results suggest the potential role of the immune response against Spike and of allergic pathways rather than humoral autoimmunity against common autoantibodies in long COVID CVD.

Tilt table testing is commonly used to evaluate orthostatic intolerance and syncope and is typically performed with three-lead electrocardiography (ECG) monitoring, which limits P-wave interpretation. A 21-year-old woman with congenitally corrected transposition of the great arteries presented with recurrent tachy-palpitations and near syncope and was presumed to have postural tachycardia syndrome (POTS) after extensive noninvasive testing. During head-up tilt table testing incorporating intermittent 12-lead ECGs, she developed a sustained narrow-complex tachycardia that reproduced her symptoms. Careful P-wave analysis demonstrated P-wave morphologies that localized the rhythm to a left atrial focus, which was later confirmed on an electrophysiology study. This case highlights the diagnostic value of 12-lead ECGs during tilt table testing for the analysis of P-wave morphology and axis. Ectopic atrial tachycardia may mimic orthostatic syndromes and remain undetected with limited-lead testing. Incorporation of 12-lead ECGs during tilt table testing enables ECG-based localization of atrial arrhythmias, preventing misdiagnosis of orthostatic syndromes.

Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily affects female patients. There are scarce data evaluating the long-term outcomes in POTS. This study sought to evaluate the long-term impacts of POTS over multiple decades in adult patients. Past research participants at the VUMC Autonomic Dysfunction Center Research Unit (symptomatic ≥10 years) were recruited to participate in the study. A custom survey was administered at one time point. Participants were grouped as IMPROVED or NOT IMPROVED based on symptom course over time. Continuous data are reported as median (25th, 75th). Patients with POTS (n = 44; 98% female) were included in the analysis (62% response rate). Patient age at the time of survey was 48 (38, 54) years, with 23 (15, 27) years from POTS symptom onset, and 17 (12, 24) years from POTS diagnosis. Since diagnosis, symptoms completely resolved in 2%, improved in 46%, worsened in 25%, were unchanged in 11%, and demonstrated a variable symptom course in 16%. Patients who were NOT IMPROVED were more likely than those IMPROVED to have neuropathy, gastroparesis, and overactive bladder symptoms. In a cohort of adult patients with POTS who received care at a national referral center for autonomic disorders, almost half reported their POTS symptoms as improved 10 or more years after symptom onset. Most patients with POTS experienced ongoing symptoms for many years after diagnosis.

Postural orthostatic tachycardia syndrome (POTS) is associated with multiple autonomic symptoms, including gastrointestinal (GI) complaints, and has been linked to insulin resistance. We aimed to explore HbA1c, circulating metabolic hormones (insulin, C-peptide, GIP, GLP-1, glucagon, leptin, and peptide YY) and cortisol, and their associations with hemodynamic parameters and GI symptoms in POTS. Two POTS cohorts were studied and compared with matched controls. In the fasting cohort, blood samples were drawn in 42 patients and 41 controls, followed by active standing tests with measurement of pulse and blood pressure (BP) in supine and standing positions. In the non-fasting cohort, questionnaires assessed GI symptoms and HbA1c was measured in 43 patients and 52 controls. Fasting C-peptide and insulin levels correlated with BP in POTS (q = 0.002) but not in controls. Fasting insulin tended to be higher in POTS but was not statistically significant after adjustment for BMI (β = 6.85; 95% CI: -1.04-14.74; p = 0.085). Morning cortisol was comparable between groups. In the non-fasting cohort, HbA1c and metabolic hormones were comparable between groups, with no associations with GI symptoms. Together, these findings suggest a potential link between insulin-related pathways and BP regulation in POTS. Future studies are warranted to further investigate insulin dynamics in POTS.

Cardiac arrhythmias remain a major cause of morbidity and mortality, and current therapies have notable limitations. Vagus nerve stimulation (VNS), which modulates autonomic tone, has emerged as a potential adjunctive treatment. This systematic review evaluated the efficacy of invasive and noninvasive VNS in patients with atrial fibrillation, heart failure, myocardial infarction, and other rhythm disorders. A search of PubMed, Scopus, and Web of Science identified 21 randomized controlled trials, including 11,368 patients. Overall, VNS was associated with reduced atrial fibrillation incidence and burden, improved autonomic function and left ventricular ejection fraction in heart failure, and reduced arrhythmic events and infarct biomarkers after myocardial infarction. Additional benefits were observed in conditions such as vagally mediated atrioventricular block and postural orthostatic tachycardia syndrome. Across studies, VNS demonstrated a favorable safety profile. These findings suggest that VNS may be a promising multimodal strategy for reducing arrhythmia burden and improving cardiac autonomic regulation, although larger confirmatory trials are needed.