Postural orthostatic tachycardia syndrome (POTS) is a type of autonomic dysfunction that can occur following coronavirus disease (COVID-19) infection, particularly in adolescents. Treatment options are limited and often ineffective. We report a case of long COVID-associated POTS that responded favorably to epipharyngeal abrasive therapy (EAT), a treatment targeting chronic inflammation in the epipharynx. A previously healthy adolescent developed persistent fatigue, headache, dizziness, insomnia, and orthostatic intolerance lasting over 3 months after a COVID-19 infection. The symptoms severely impaired daily functioning, rendering the patient bedridden. Based on clinical symptoms and a positive orthostatic test showing excessive postural tachycardia without hypotension, the patient was diagnosed with POTS associated with long COVID. Chronic epipharyngitis was also noted upon endoscopic examination. The patient underwent weekly sessions of EAT for a total of 120 days. No additional pharmacologic treatment was provided during this period. The patient showed marked improvement in symptoms, including increased tolerance to standing, reduced fatigue, and improved sleep quality. Objective improvement was confirmed through repeat orthostatic testing. The patient resumed school attendance and daily activities without limitation. This case highlights the potential effectiveness of EAT in treating long COVID-related POTS in adolescents. EAT may offer a nonpharmacological treatment option by addressing underlying chronic epipharyngeal inflammation, a possible contributor to autonomic dysfunction.

Referring to a broad spectrum of the autonomic symptoms, autonomic disorders, and general dysfunction of the autonomic nervous system, dysautonomia is one of the common and under-recognized comorbidities of a wide variety of systemic disease, including diabetes, autoimmune disorders, vitamin deficiencies, and hormonal dysregulation. The most common autonomic disorders encountered in clinical practice are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be undiagnosed or often mislabeled with psychiatric disorders. Typical clinical features of dysautonomia, such as orthostatic dizziness/lightheadedness, orthostatic intolerance, palpitations, exercise intolerance, cognitive dysfunction, and fatigue, should prompt a diagnostic investigation for dysautonomia, which includes an in-office 10-min stand test or a tilt table test in conjunction with other autonomic function tests if available. Treatment approach consists of non-pharmacologic and pharmacologic therapies with beta blockers, midodrine, ivabradine, pyridostigmine, fludrocortisone, stimulants, and other medications. In clinical setting, dysautonomia may present a diagnostic and therapeutic challenge in patients with various systemic disorders and may require a high index of suspicion on the part of the clinician. Importantly, diagnosing and treating dysautonomia is critical to providing comprehensive and personalized medical care to complex patients with chronic illness, who are typically highly symptomatic with multi-systemic complaints as a result of comorbid, and often undiagnosed, dysautonomia.

Ivabradine selectively reduces heart rate by inhibiting the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel in the sinoatrial node. Unlike other medications that produce negative chronotropic effects [beta-blockers, calcium channel blockers], ivabradine does not affect systemic, pulmonary, and coronary hemodynamics. Despite several proof-of-concept clinical studies suggesting that ivabradine may exert anti-ischemic effects, two large randomized trials did not support its use in patients with chronic stable angina. Preliminary data also did not support the use of ivabradine in patients with acute ST-segment elevation myocardial infarction or acutely decompensated heart failure. However, ivabradine improved outcome in patients with heart failure with reduced ejection fraction (HFrEF), leading to its approval by the Food and Drug Administration, but the drug failed to do so in those with heart failure with preserved ejection fraction (HFpEF). Ivabradine may also be useful in cardiac electrophysiology disorders characterized by tachycardia (e.g., inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome), but it has not yet gained wide acceptance for these indications. In this article, the authors briefly review the structure and function of the cardiac HCN channel; discuss the development and actions of drugs, including ivabradine, that modulate the channel's activity; describe in detail the potential clinical applications of ivabradine in patients with coronary artery disease, HFrEF and HFpEF, and cardiac electrophysiology; comment on the adverse effects of ivabradine therapy; and finally, consider the potential anesthetic implications of ivabradine in patients undergoing noncardiac and cardiac surgery.

Cardiovascular autonomic dysfunction is a major complication in a large proportion of patients with long coronavirus disease (LC). As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection. This study aimed to develop and test a 24-hour electrocardiogram (ECG) recording to direct the clinical suspicion toward the diagnosis of POTS. Consecutive patients referred to the Karolinska University Hospital in Stockholm from April 2021 to April 2022 were included. Patients with POTS were compared with patients with LC without POTS (verified by active standing tests) and control healthy subjects according to 3 specific analyses based on 24-hour ECG recording: (1) heart rate (HR) spikes of > 30 beats per minute, (2) awakening HR increase, and (3) HR variability (root mean square of successive difference). The control group consisted of healthy subjects from the database of the University Hospital of Saint-Etienne. A total of 100 patients with LC (mean age, 42.54 ± 10.45 years; 92% women) and 100 healthy subjects (41.40 ± 7.21 years; 96% women) were included. LC POTS (n = 45) was associated with (1) a higher number of HR spikes/h (1.47 ± 0.84 vs 0.68 ± 0.50 and 0.40 ± 0.28/h; < .01), (2) an abrupt and sustained increase in HR after awakening ( < .05), and (3) a reduction of HR variability: mean root mean square of successive difference of 34.90 ± 12.48 vs 30.47 ± 19.15 and 43.35 ± 21.10 ms ( < .01) compared with patients with LC without POTS (n = 55) and healthy subjects. A triple analysis of 24-hour ECG recordings could reveal a characteristic POTS signature in LC. More research in other populations is needed to draw any firm conclusions about its generalizability.

The objective of the review is to systematically map the literature on non-pharmacological interventions for postural orthostatic tachycardia syndrome to identify and categorize interventions used, and highlight research gaps to guide future studies. Postural orthostatic tachycardia syndrome is characterized by an excessive increase in heart rate upon standing and symptoms of orthostatic intolerance. Non-pharmacological interventions are first-line treatments; however, the breadth, characteristics, and gaps in the current evidence base have not been systematically mapped, making this scoping review necessary to guide future research directions. Studies on non-drug, non-procedural, and non-invasive interventions for postural orthostatic tachycardia syndrome in both children and adults will be included. Direct (affecting patients) and indirect (benefiting but not targeting patients) interventions in any setting will be considered. Original research, systematic reviews, meta-analyses, and gray literature will be included. A comprehensive search will be conducted across 6 databases (MEDLINE [Ovid], Embase [Ovid], Cochrane Library, CINAHL [EBSCOhost], Scopus, and Web of Science Core Collection) and gray literature platforms. Searches will be limited to articles in English, Afrikaans, French, German, and Korean, with no restriction on publication date. Two reviewers will independently screen titles and abstracts, as well as full texts, against the eligibility criteria. Data will be extracted using a standardized tool and presented to highlight key findings and research gaps. The initial data extraction form was developed after scanning the literature and will be iteratively refined as part of protocol development. OSF https://osf.io/cg365.

Postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS) are often reported to occur concurrently with mast cell activation disorders (MCADs) and hereditary alpha tryptasemia (HAT). However, it remains unclear whether evidence supporting this relationship exists. To determine the prevalence of MCADs and HAT in patients diagnosed with having EDS and or POTS. We conducted a systematic search of MEDLINE (OVID), EMBASE (OVID), Scopus, and Web of Science with the assistance of an experienced medical librarian. We focused on patients with any MCAD or HAT in conjunction with a diagnosis of POTS and/or EDS. A total of 200 records were screened, 107 were excluded based on the title or abstract, 92 full texts were reviewed, and 1 record was not retrieved. No studies were identified that met our primary criterion of including patients diagnosed with any MCAD or HAT alongside POTS and/or EDS based on our prespecified diagnostic criteria. Our review did not find evidence to confirm a relationship between MCADs, HAT, POTS, and EDS. However, it must be mentioned that 1 study revealed an association between mast cell activation syndrome, POTS, and EDS and came close to meeting the full diagnostic criteria for mast cell activation syndrome, unlike other studies. This indicates that further research using strict and validated diagnostic criteria is needed to clarify whether a true association between conditions exists.

Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of tachycardia on standing leading to palpitations, dizziness, chest pain, and/or fatigue. An exaggerated norepinephrine response with standing is often present in POTS, but it remains unclear whether the tachycardia is compensatory for a reduced stroke volume or whether the tachycardia is itself causing the symptoms of POTS. We herein report the effects of heart rate (HR) lowering with ivabradine, a selective I f channel blocker, on symptom burden in patients with POTS. After ivabradine treatment, there was a significant reduction in the change in HR with standing in all patients from 40 (30-70) to 15 (8-19) bpm ( P = 0.011), without significant changes in blood pressure. The Malmö score was significantly reduced in all patients from 86 (74-92) to 39 (32-66) ( P = 0.005). A correlation between change in HR with standing and the change in Malmö score (R = +0.828; R 2 quadratic = 0.635; P < 0.001) was present. The parallel improvement in HR response and symptoms with ivabradine suggests that the tachycardia response in POTS may not be considered compensatory but rather central to the pathophysiology of POTS symptoms.

The purpose of this Clinical Practice Update Expert Review is to describe key principles in the evaluation and management of patients with disorders of gut-brain interaction (DGBI) and hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSDs) with coexisting postural orthostatic tachycardia syndrome (POTS) and/or mast cell activation syndrome (MCAS). This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Clinicians should be aware of the observed associations between hEDS or HSDs and POTS and/or MCAS and their overlapping gastrointestinal (GI) manifestations; while theoretical explanations exist, experimental evidence of the biological mechanisms that explain relationships is limited and evolving. BEST PRACTICE ADVICE 2: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of POTS/MCAS, but universal testing for POTS/MCAS in all patients with hEDS/HSDs is not supported by the current evidence. BEST PRACTICE ADVICE 3: Gastroenterologists seeing patients with DGBI should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS (https://www.ehlers-danlos.com/wp-content/uploads/2017/05/hEDS-Dx-Criteria-checklist-1.pdf) or offer appropriate referral to a specialist where resources are available. BEST PRACTICE ADVICE 4: Testing for POTS through postural vital signs (eg, symptomatic increase in heart rate of 30 beats/min or more with 10 minutes of standing during an active stand or head-up tilt table test in the absence of orthostasis) and referral to specialty practices (eg, cardiology or neurology) for autonomic testing should be considered in patients with hEDS/HSDs and refractory GI symptoms who also report orthostatic intolerance after exclusion of medication side effects and appropriate lifestyle or behavioral modifications (eg, adequate hydration and physical exercise) have been attempted but is not required for all patients with hEDS/HSDs who report GI symptoms alone. BEST PRACTICE ADVICE 5: In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS/HSDs and DGBI who also present with episodic symptoms that suggest a more generalized mast cell disorder (eg, visceral and somatic pain, pruritus, flushing, sweating, urticaria, angioedema, wheezing, tachycardia, abdominal cramping, vomiting, nausea, diarrhea, urogynecological and neurological complaints) involving 2 or more physiological systems (eg, cutaneous, GI, cardiac, respiratory, and neuropsychiatric), but current data do not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS/HSDs without clinical or laboratory evidence of a primary or secondary mast cell disorder. BEST PRACTICE ADVICE 6: If MCAS is suspected, diagnostic testing with serum tryptase levels collected at baseline and 1-4 hours following symptom flares may be considered by the gastroenterologist; increases of 20% above baseline plus 2 ng/mL are necessary to demonstrate evidence of mast cell activation. BEST PRACTICE ADVICE 7: If a diagnosis of MCAS is supported through clinical and/or laboratory features, patients should be referred to an allergy specialist or mast cell disease research center where additional testing (eg, urinary N-methylhistamine, leukotriene E4, 11β-prostaglandin F2) may be performed. BEST PRACTICE ADVICE 8: Diagnostic evaluation of GI symptoms consistent with DGBI in patients with hEDS/HSDs and comorbid POTS and/or MCAS should follow a similar approach to the evaluation of DGBI as in the general population including the use of a positive symptom-based diagnostic strategy and limited noninvasive testing. BEST PRACTICE ADVICE 9: Testing for celiac disease may be considered earlier in the diagnostic evaluation of patients with hEDS/HSDs who report a variety of GI symptoms and not only limited to those with diarrhea. There is insufficient research to support routine testing for disaccharidase deficiencies or other diet-mediated mechanisms as causes of GI symptoms in hEDS/HSDs. BEST PRACTICE ADVICE 10: Diagnostic testing for functional defecation disorders with anorectal manometry, balloon expulsion test, or defecography should be considered in patients with hEDS/HSDs and lower GI symptoms such as incomplete evacuation given the high prevalence of pelvic floor dysfunction, especially rectal hyposensitivity, in this population. BEST PRACTICE ADVICE 11: In patients with hEDS/HSDs and comorbid POTS who report chronic upper GI symptoms, timely diagnostic testing of gastric motor functions (eg, measurement of gastric emptying and/or accommodation) should be considered after appropriate exclusion of anatomical and structural diseases, as abnormal gastric emptying may be more common than in the general population. BEST PRACTICE ADVICE 12: Medical management of GI symptoms in hEDS/HSDs and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results. In addition to general DGBIs and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS. BEST PRACTICE ADVICE 13: Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures. BEST PRACTICE ADVICE 14: When MCAS is suspected, patients can benefit from treatment with histamine receptor antagonists and/or mast cell stabilizers, in addition to avoiding triggers such as certain foods, alcohol, strong smells, temperature changes, mechanical stimuli (eg, friction), emotional distress (eg, pollen, mold), or specific medications (eg, opioids, nonsteroidal anti-inflammatory agents, iodinated contrast). BEST PRACTICE ADVICE 15: Besides general nutritional support, special diets including a gastroparesis diet (ie, small particle diet) and various elimination diets (eg, low fermentable carbohydrates, gluten- or dairy-free, low-histamine diets) can be considered for improving GI symptoms. Dietary interventions should be delivered with appropriate nutritional counseling or guidance to avoid the pitfalls of restrictive eating. BEST PRACTICE ADVICE 16: Management of chronic GI symptoms in patients with hEDS/HSDs who do not exhibit symptoms consistent with POTS or MCAS should align with existing approaches to management of DGBI and GI motility disorders in the general population, including integrated multidisciplinary care involving multiple specialties, where appropriate (eg, cardiology, rheumatology, dietician, psychology).

The utility of ambulatory blood pressure monitoring (ABPM) among patients with various forms of autonomic dysfunction (AD) is unknown. Twenty-four-hour ABPM among patients with postural orthostatic tachycardia syndrome (POTS), AD without POTS, and control patients without AD were compared. Patients with AD without POTS had high rates of uncontrolled blood pressure (76%), whereas 19% of patients with POTS had uncontrolled blood pressure, suggesting ABPM may provide less value among patients with POTS.

Pediatric concussion can affect the autonomic nervous system. Understanding the prevalence and characteristics of physiological autonomic dysregulation (AD) and symptom provocation following concussion is crucial for optimizing recovery and developing targeted interventions. To determine the prevalence of AD and symptom provocation upon postural change and to (1) explore the overlap between AD and symptom provocation, (2) apply adult orthostatic tachycardia criteria (heart rate [HR] ≥30 bpm) to this pediatric population, (3) explore associations of demographic and injury characteristics with AD and symptom provocation, and (4) characterize AD presentation and identify the predominant orthostatic sign. This retrospective cohort study used electronic medical record review of clinical data at tertiary care concussion clinics that operate as a learning health system in Canada. Patients aged 5 to younger than 18 years who presented to those clinics within 45 days of a diagnosed concussion between August 2022 and January 2024 were included. Analysis was conducted from April to October 2024. Diagnosis of concussion. Primary outcomes were AD presence (defined as the presence of either a decrease in systolic BP [≥20 mm Hg], decrease in diastolic BP [≥10 mm Hg], or increase in HR [≥40 bpm]), and symptom provocation (new or worsening). HR, blood pressure (BP), and symptoms were measured after a 2-minute supine rest and 1 minute of unsupported standing. Of 764 eligible patients, 451 (231 female [51.22%]; 129 [28.60%] aged 5-11 years and 322 [71.40%] aged 12 to <18 years) were included; objective AD was identified in 45 patients (9.98%; 95% CI, 7.54%-13.09%), primarily by HR changes (22 of 45 patients [48.89%]). When applying adult tachycardia criteria, AD prevalence was 23.73% (95% CI, 20.03%-27.88%). Orthostatic symptom provocation occurred in 103 of 445 patients (23.15%; 95% CI, 19.47%-27.28%). Among 134 patients with either AD or symptom provocation, 12 (8.96%) exhibited both. Patients with AD had higher rates of neurodevelopmental disorders than patients without AD (15 of 45 patients [33.33%] vs 75 of 406 patients [18.47%]; P = .02), while symptom provocation was associated with female sex (63 of 103 patients [61.17%] vs 166 of 342 patients [48.54%]; P = .03), preexisting mental health disorders (28 of 103 patients [27.18%] vs 45 of 342 patients [13.16%]; P < .001), higher concussion symptom burden (median [IQR] symptom intensity score, 46.00 [16.00-67.00] vs 21.00 [6.00-46.00]; P < .001), and status of posttraumatic amnesia at injury (22 of 103 patients with posttraumatic amnesia [22.68%] vs 63 of 342 patients without [18.92%]; P = .009). In this cohort study of children and adolescents with concussion, approximately 1 in 10 exhibited AD and 1 in 4 exhibited symptom provocation. The observed low concordance between physiological AD and symptom provocation, along with their distinct clinical profiles, might suggest these represent separate phenomena in pediatric concussion; future research should explore whether incorporating both measures into clinical assessments enhances understanding of concussion and informs targeted interventions to optimize recovery.

Exercise training is recommended as a complementary treatment in postural orthostatic tachycardia syndrome (POTS) according to international guidelines. However, less is known regarding how exercise training could successfully be implemented in clinical practice in patients with POTS. Thus, in the current study, we aim to assess the effect of a 16-week tailored exercise training programme in POTS. A total of 200 patients diagnosed with POTS will be recruited. The study will be conducted as a randomised cross-over study. POTS symptoms will be evaluated using the Malmö POTS Symptom Score, Orthostatic Hypotension Questionnaire and 36-item Short Form Health Survey. Haemodynamic parameters will be evaluated by orthostatic tests and maximum working capacity evaluated by bicycle exercise test. Symptoms, haemodynamic parameters and exercise capacity will be assessed before and after a 16-week training programme. The study was approved by the Swedish ethical review authority (2022-03186-01) and all procedures will be performed in accordance with the Helsinki Declaration. Results will be made available to patients with POTS, healthcare professionals, the funders and other researchers in publicly available (open access) medical journals. NCT05554107, registered on 26 September 2022.

There is limited data on well-documented comorbidities with polysomnography (PSG)/multiple sleep latency test (MSLT) findings in idiopathic hypersomnia (IH). We aimed to characterize the clinical, PSG/MSLT characteristics of IH patients in our health network. : We reviewed charts of all IH cases between 2000 and 2023, extracting clinical features, comorbidities, and PSG/MSLT findings. One hundred forty-two patients (83.80% female) with IH were included. Compared to those without mood disorders, both major depressive disorder (MDD) and anxiety patients were older at onset (27.10 ± 8.32 and 26.76 ± 8.40 versus 23.23 ± 6.94 and 24.05 ± 7.31 years; = 0.003 and = 0.042) and had lower ESS (15 versus 19; 15.67 versus 17.75; < 0.0001), more disrupted sleep (28 (36.36%) versus 8 (12.31%); = 0.001; 24 (35.82%) versus 12 (16%); = 0.007), and less sleep inertia (30 (38.96%) versus 38 (58.46%); = 0.021; 26 (38.81%) versus 42 (56%); = 0.04). Fifteen patients with dysautonomia disorders presented at an earlier age (21.80 ± 6.60 versus 25.75 ± 8, = 0.0682). On MSLT, MDD, anxiety, and dysautonomia patients had longer sleep latencies than the non-affected counterparts (6.40 (5.40-7.60) minutes versus 3.60 (2.60-5.40) min., <0.0001; 6.20 (5.20-7.40) versus 4 (2.60-6.40) minutes; < 0.0001; 7.40 (6-7.80) versus 5.40 (3-7); = 0.008). MDD and anxiety cases had fewer sleep onset REM periods (7 (9.09%) versus 16 (24.62%), = 0.0124 and 6 (8.96%) versus 17 (22.67%), = 0.0388) compared to those not affected by these disorders. Our study highlights the importance of recognizing mood disorders and dysautonomia in patients diagnosed with IH. Further research may elucidate management strategies for these patients.

We sought to determine: 1.) the relationship between headache frequency and autonomic reflexes, and 2.) mechanisms underlying orthostatic intolerance (OI) in patients with migraine. Adults with migraine (N = 30) underwent autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal/adrenergic baroreflex sensitivity (BRS-V/A). Postural Orthostatic Tachycardia Syndrome (POTS) and orthostatic hypotension/hypertension were diagnosed during tilt table testing. A cold pressor test (CPT) evaluated sympathetic vasomotor function. Participants completed the Migraine Disability Assessment (MIDAS), the 2011 Fibromyalgia (FM) Survey Criteria, chronic overlapping pain condition (COPC) screener, and Compass-31. Monthly headache days correlated with CASS (p = 0.001), BRS-V (p < 0.001), and the systolic blood pressure response to CPT (p = 0.003) in the expected direction with increasing ANS reflex dysfunction correlating to increasing number of headache days. During tilt testing, OI was prevalent (25/30; 83%) and reported by all patients with chronic migraine. An abnormal cardiovascular response to tilt was present in the majority (63%) of which POTS was the most common etiology (56.2%). Patients reporting OI during tilt table testing despite a cardiovascular response (33%) had higher FM scores (15.8 ± 3.6 vs. 7.5 ± 4.6; p < 0.01) and a greater prevalence of non-headache COPCs (88.8% versus 20.0%, p = 0.02), compared to participants who were asymptomatic during tilt. There are two etiologies of OI in patients with migraine: 1.) an abnormal cardiovascular response to tilt (concordant OI) and, 2.) sensory hypersensitivity (discordant OI).

Patients with hereditary alpha-tryptasemia (HαT) have been shown not only to be more prone to anaphylaxis but also to more severe reactions. The relationship between hypermobility, gastroparesis, gastroesophageal reflux disease (GERD), postural orthostatic tachycardia syndrome (POTS), and HαT has been variably described in the literature although no causal biochemical or genetic link has been identified. Herein, we sought to describe the clinical presentation, treatment, and co-morbidities of patients diagnosed with HαT within the Penn State Health System. Through a retrospective cross-sectional chart review, we report  the clinical and therapeutic characteristics of patients who tested positive for HαT genotypes (2α3β, 3α2β) within Penn State Health. Twenty-six percent of patients within our cohort had co-occurring diagnoses of hypermobility (7, 26.9%), or POTS (7, 26.9%) while more than half of patients had GERD (15, 57.7%). Anaphylaxis was reported among 7 (26.9%) with the average number of anaphylactic episodes per patient prior to HαT identification being less than one. Patients with triplication had higher prevalence of hypermobility and POTS and were more likely to receive treatment with omalizumab or cromolyn. Co-morbid hypermobility, POTS and GERD in patients with flushing, urticaria, or anaphylaxis should warrant further investigation for HαT.

To revisit the pharmacology and real-world use of carbidopa in the management of autonomic disorders. To identify articles suitable for this review, a search of the PubMed database was conducted in January 2025 using the keywords "Carbidopa," "MK-486," and "L-alpha-methyldopa hydrazine." The pharmacotherapeutic role of carbidopa extends beyond the management of Parkinson's disease. Our literature search revealed the use of carbidopa in three primary autonomic diseases to treat either nausea or symptoms of sympathetic hyperactivity: (1) familial dysautonomia, (2) hyperadrenergic postural orthostatic tachycardia syndrome (POTS), and (3) afferent baroreflex failure (familial or acquired). Even at a dose as high as 600 mg/day, carbidopa was not associated with bothersome side effects in some of the clinical trials on familial dysautonomia. Pre-clinical evidence also suggests in vitro and in vivo inhibition of T-cell activation by carbidopa and a potential therapeutic use in cytokine release syndrome. Current evidence, although limited, suggests that carbidopa has a favorable safety profile. While large, well-designed studies are warranted, observations from case series and small studies suggest that carbidopa could have utility in treating nausea in familial dysautonomia and symptoms of sympathetic hyperactivity in hyperadrenergic postural orthostatic tachycardia syndrome (POTS) and afferent baroreflex failure.

Postural orthostatic tachycardia (POTS) and orthostatic hypotension (OH) commonly occur after hematopoietic stem cell transplantation (HSCT). This study sought to determine the prevalence of POTS and OH before HSCT and the incidence of new cases after HSCT. In this single-center, prospective study, patients were evaluated 30 days before and 30 and 100 days after HSCT. Blood pressure, heart rate, and plasma norepinephrine levels were measured in the supine position and after a 10-minute active stand test to assess for POTS or OH. After HSCT, adrenergic receptor (AR)-modulating autoantibody activity was measured in 8 subjects with POTS and 8 without. Among 46 patients, 40 (87.0%) underwent autologous and 6 (13.0%) allogeneic HSCT. Multiple myeloma was the most common indication (67.4%). Before HSCT, the prevalence of both POTS and OH was 4.3%. At 30 days after HSCT, POTS was present in 10 (25.6%) of 39 patients, including 9 (23.1%) new cases, and OH in 6 (15.4%), including 5 (12.8%) new cases. Patients with POTS at 30 days showed a significantly greater increase in norepinephrine levels upon standing (median 231% [Q1-Q3: 179%-343%]) compared with before HSCT (median 100% [Q1-Q3: 62%-183%]) (P = 0.005), which positively correlated with heart rate changes. AR-modulating autoantibody activity was also higher in patients with POTS vs those without and directly correlated with heart rate changes. Approximately 1 in 4 patients developed POTS after HSCT, characterized by exaggerated increases in norepinephrine upon standing and elevated AR-modulating autoantibody activity.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous collection of disorders that correspond to autonomic dysfunction. Until recently, it was mostly unresolved as a clinical issue. Our study investigated autonomic function in patients with POTS. The research utilizes both pre-test 24-hour Holter monitoring to evaluate heart rate variability (HRV) and instantaneous HRV during the head-up tilt test (HUTT), aiming to discern differences in autonomic nervous system (ANS) function between patients positively diagnosed with POTS and those exhibiting negative HUTT results. The 24-hour Holter results derived from time-domain methods demonstrated that SDNN, SDANN, SDNN index, rMSSD, pNN50, and TINN were significantly elevated in the POTS positive group compared to the HUTT-negative group. Meanwhile, frequency-domain methods revealed that low-frequency and high-frequency were significantly elevated in the POTS-positive group relative to the HUTT-negative group. However, the analysis of instantaneous time-domain and frequency-domain parameters during HUTT, including SDNN, RMSSD, SDSD, PNN50, VLF, LF, and HF, revealed no statistically significant differences. The findings suggest that pre-HUTT HRV, as assessed by 24-hour Holter monitoring, may provide greater clinical relevance in distinguishing between these groups. The study reveals that patients with POTS demonstrate abnormalities in autonomic regulation, characterized by a decrease in sympathetic activity alongside an increase in parasympathetic activity. The dysregulation of autonomic balance likely contributes to the elevated incidence of syncope and presyncope events observed in patients with POTS.

Introduction  Low-dose naltrexone (LDN) has been studied in recent years as a novel off-label therapy for several conditions under the umbrella of dysautonomia, which is defined as disorders affecting the autonomic nervous system (ANS), including postural orthostatic tachycardia syndrome (POTS). Naltrexone has a paradoxical pain-reducing effect in low doses due to transient opioid receptor blockage that increases compensatory endogenous opioid signaling. It is also thought that LDN may improve autonomic symptoms by reducing microglial activation via TLR-4 antagonism and subsequently counteracting central sensitization. Patients with dysautonomia often experience comorbidities such as small fiber neuropathy and fibromyalgia. The goal of this study was to gain a better understanding of LDN's impact on autonomic symptoms and pain in patients with dysautonomia.  Methods In this chart review, we analyzed the records of 29 patients diagnosed with dysautonomia (general, POTS, or stiff person syndrome). Information collected included demographics, comorbidities, reasons for LDN prescription, LDN dose (initial and final), documented pain changes, and Composite Autonomic Symptom Score-31 (COMPASS-31). COMPASS-31 is a validated questionnaire used to measure autonomic symptom burden. COMPASS-31 scores (including subsections) were collected from patients during their initial visit to our tertiary care autonomic center, the visit when LDN was prescribed, and a follow-up visit three to nine months later. Student's t-test was used to determine statistical significance between COMPASS-31 scores from the initial visit and the LDN prescription visit, as well as between the LDN prescription visit and the follow-up visit.  Results  The most common reason for prescribing LDN to patients in this study was pain or fibromyalgia (61.11%), followed by orthostatic intolerance (27.78%). Improvement in pain was documented for seven patients (24.14%) at the follow-up visit after starting LDN. Most patients (86.21%) began LDN at a dose of 1 mg daily, but 11 subjects had an increased dose by their follow-up visit. No statistical significance was seen when comparing average COMPASS-31 total and subsection scores between the initial visit and the LDN prescription visit or between the LDN prescription visit and the follow-up visit. LDN therapy was largely tolerated with five patients reporting mild side effects. Conclusion  LDN may be prescribed for patients with dysautonomia either due to autonomic dysfunction or pain. Patients might show improvement in pain within a matter of months, but the reason why some respond better than others remains unclear. Future studies are needed to understand how LDN can impact autonomic symptoms on an individual level. With further investigation, we might discover predictors of a strong therapeutic effect from LDN in patients with dysautonomia.

Postural orthostatic tachycardia syndrome (POTS) is characterized by exaggerated orthostatic tachycardia in the absence of orthostatic hypotension. The pathophysiology of POTS may involve hypovolemia, autonomic neuropathy, a hyperadrenergic state, and cardiovascular deconditioning, any of which can co-occur in the same patient. Furthermore, there is growing evidence of the role of autoimmunity in a subset of POTS cases. In recent years, investigators have described an increased rate of autoimmune comorbidities as evidenced by the finding of several types of neural receptor autoantibody and non-specific autoimmune marker in patients with POTS. In particular, the association of the disease with several types of anti-G protein-coupled receptor (GPCR) antibodies and POTS has frequently been noted. A previous study reported that autoantibodies to muscarinic AChRs may play an important role in POTS with persistent, gastrointestinal symptoms. To date, POTS is recognized as one of the sequelae of coronavirus disease 2019 (COVID-19) and its frequency and pathogenesis are still largely unknown. Multiple autoantibody types occur in COVID-related, autonomic disorders, suggesting the presence of autoimmune pathology in these disorders. Herein, we review the association of anti-GPCR autoantibodies with disorders of the autonomic nervous system, in particular POTS, and provide a new perspective for understanding POTS-related autoimmunity.

Autonomic dysfunction is a common and often debilitating feature of long-COVID (LC), however, studies evaluating frequency and severity of chronic autonomic dysfunction in LC are limited. We utilized an established online cohort of participants with LC to assess duration and severity of autonomic dysfunction, impact on quality of life, risk factors of autonomic diagnoses including postural tachycardia syndrome (POTS), and efficacy of common treatments. Our international cohort included 526 adults with LC aged 20-65 years who previously completed baseline evaluations of LC symptoms, autonomic symptom burden, and quality of life. Participants repeated survey instruments and completed new instruments assessing risk factors and symptom mitigation strategies. A subset of individuals completed a 10-min active stand test. Multivariable logistic regression identified predictors of autonomic symptom burden and incident autonomic diagnoses including POTS. A total of 71.9% of participants with LC had a Composite Autonomic Symptom Score-31 (COMPASS-31) score ≥ 20, suggestive of moderate-to-severe autonomic dysfunction. The median symptom duration was 36 [30-40] months, and 37.5% of participants could no longer work or had to drop out of school due to their illness. In addition, 40.5% of individuals with autonomic dysfunction were newly diagnosed with POTS, representing 33% of the total LC cohort. Female sex and joint hypermobility were associated with an increased risk of autonomic dysfunction. Evidence of chronic moderate-to-severe autonomic dysfunction was seen in most participants with LC in our cohort and was significantly associated with reduced quality of life and functional disability. POTS was the most common post-COVID autonomic diagnosis.

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with serious health consequences, while its etiology remains largely elusive. The purpose of this study was to investigate the genetic landscape of POTS using genomic approaches in a unique pediatric cohort. We conducted a combined genome wide genotyping and whole exome sequencing (WES) study to systemically examine the molecular mechanisms of POTS pathogenesis. The patients were genotyped as two independent cohorts: a family cohort of 100 complete families and a case-control cohort of 207 unrelated European cases and 4063 ethnicity-matched control subjects. The WES component consisted of a subset of the genotyped subjects, including 87 unrelated European cases and 2719 unrelated European control subjects. The heterogeneous phenotype of POTS made achieving genome-wide significance improbable. Instead, 5670 SNPs with nominal significance (P < 0.05) were identified in both the family and case-control cohorts, with effects in the same direction. We conducted an over-representation analysis (ORA) by considering all genes that showed nominal significance. The ORA identified gene sets linked to cell-cell junction, early estrogen response, and substance-related disorders with statistical significance. Moreover, WES revealed 55 genes with genome-wide significance through rare variant burden analysis, harboring 92 variants classified as pathogenic or likely pathogenic by ClinVar. This study showcases the complex interplay between common and rare genetic variants in POTS development, marking a pioneering step forward in deciphering its complex etiologies. The insights from this research enrich our understanding of POTS, offering new avenues for precise treatment strategies and highlighting areas for further research.

To explore the significance of anxiety and depression in children with postural tachycardia syndrome (POTS). The study enrolled seventy-one children diagnosed as POTS in Beijing Children's Hospital Affiliated to Capital Medical University and Kaifeng Children's Hospital, aged 13 ± 2 years; The Self-Rating Depression Scale (SDS), the Self-Rating Anxiety Scale (SAS), the Hamilton Depression (HAMD) scale, and the Hamilton Anxiety (HAMA) scale were determined in POTS children. The POTS children were divided into two groups: anxiety/ depression group and non- anxiety / depression group according to the above scales scores. Heart rate (HR), and blood pressure (BP)were monitored by a Dash 2000 Multi-Lead Physiological Monitor. Twenty POTS children consisted of anxiety / depression group. Twelve were girls and eight were boys, with mean age of 14 ± 2 years. The non- anxiety / depression group included fifty-one POTS children aged 12 ± 2 years. Twenty-six were girls and twenty-five were boys. There were no statically differences in weight, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR in supine. The age and height of anxiety / depression group were higher than that in non- anxiety / depression group. The maxium HR (HRmax) in ten minutes of upright position or tilt, the change of HR from supine to upright (ΔHR), symptom scores in anxiety / depression group were significantly higher than that in non- anxiety / depression group. Four scale scores were correlated with symptom scores and ΔHR. Anxiety and depression emotion might be involved in the pathogenesis of POTS.

Young women experience orthostatic intolerance to a greater degree than men. Numerous physiological pathways could be responsible for this intolerance in both healthy and pathophysiological conditions. This review discusses sex differences in hemodynamics, ventilation, autonomic control, and cerebral blood flow. Further, we discuss these phenomena and their potential exacerbations in postural orthostatic tachycardiac syndrome (POTS). After normalization for body size women have lower stroke volume and blood volume, and while upright women have reduced ventilation, reduced venous return likely from attenuated respiratory pump and skeletal muscle pump activity, augmented parasympathetic withdrawal, attenuated neurovascular transduction of sympathetic outflow, and increased vasodilatory capacity compared to age-matched men. Women have greater middle cerebral artery blood velocity, potentially impaired cerebral dynamic autoregulation (depending on the timing), yet similar cerebrovascular reactivity to carbon dioxide exists between the sexes. Thus, we suggest that the greater incidence of orthostatic intolerance in women is primarily due to hemodynamic control and autonomic function; however, the enhanced parasympathetic withdrawal while upright could theoretically influence cerebral vasodilatory capacity and is proposed as a possibility in need of further investigation. POTS physiology is described briefly due to its increasing prevalence via post-COVID infections. We summarize some potential physiological changes in POTS including hemodynamic and ventilatory control, and we highlight that cerebral blood flow control is impaired and likely plays a role in the symptomology of POTS.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an abnormal increase in heart rate upon standing, leading to symptoms such as dizziness, fatigue, and rapid heart rate. Time-restricted eating (TRE), which limits caloric intake to an 8-10 hour daily window, has been shown to decrease inflammation and improve immune, autonomic, and mitochondrial function, as well as cardiometabolic parameters. This single arm pilot study evaluated the effects of TRE on quality of life (QOL), heart rate, and mitochondrial function in 20 participants with POTS (≥30 bpm increase in upright heart rate) and a baseline dietary window of ≥12 hours. Following a 2-week baseline monitoring period, participants underwent a 12-week TRE intervention. Pre- and post-intervention assessments included QOL questionnaires, a 10-minute stand test, and plasma mitochondrial analysis. TRE significantly reduced heart rate increase upon standing (mean decrease: 11 bpm, p < 0.001), improved QOL metrics including POTS symptom severity (p < 0.0001), physical functioning (p = 0.02), and energy/fatigue (p < 0.01), and increased mitochondrial-derived ATP. These findings suggest TRE as a promising lifestyle intervention to improve QOL, heart rate, and mitochondrial function in POTS patients.

Headache and dizziness are common symptoms in children and adolescents, but the causes of headache/dizziness in most pediatric patients are not clearly defined. We intended to investigate the demographic and clinical features of pediatric patients with headache and/or dizziness and responses to head-up tilt test (HUTT). The demographic data and medical records of children and adolescents, with a primary complaint of headache and/or dizziness and undergoing HUTT between January 2001 and June 2023, were retrospectively reviewed and analyzed. Children and adolescents with headache and/or dizziness secondary to fever, trauma, or other obvious etiology were excluded. For those with positive responses to HUTT, the symptom score and HUTT responses were collected after treatment at follow-up. Among 2709 patients with unexplained headache and/or dizziness, 1080 (39.87%) cases presented positive responses to HUTT, whereas 1629 (60.13%) cases had negative responses. Among patients with positive responses, 930 (34.33%) cases presented a response of vasovagal syncope, 143 (5.28%) cases of postural orthostatic tachycardia syndrome, and 7 (0.26%) cases of orthostatic hypertension. Multivariate Logistic regression analysis demonstrated that females, older age, and low body mass index percentile increased the risk of being positive responses. At follow-up, HUTT results of 236 patients were collected, among which 131 (55.51%) cases turned negative HUTT responses and had headache/dizziness symptoms improved after treatment targeted autonomic dysfunction. HUTT can be applied to evaluate the autonomic function of children and adolescents with headache and/or dizziness and assess the treatment responses in those patients with autonomic dysfunction.