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 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 function is an integral part of the assessment of neurological disorders. However, pragmatically, it is often the most neglected part of neurological examination and is often limited to testing for orthostatic hypotension. Testing the autonomic nervous system may aid in the early diagnosis of neurodegenerative disorders, thereby enabling the initiation of neuroprotective strategies and resulting in improved quality of life in this group of patients. It may also enable differentiation between certain atypical parkinsonisms, such as Multiple System Atrophy and Dementia with Lewy Bodies, in which autonomic dysfunction is early and usually profound compared to Parkinson's disease. Our review focusses on the "first-line" autonomic function tests which can be done at the bedside and require use of minimal equipment and provide insights into cardiovascular, pupillary and sudomotor function. The use of minimal equipment underscores the value of these tests in resource-constrained settings as a major unmet need, thereby saving resources and avoiding delays in diagnosis and treatment.

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/commentary 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 Head-Up Tilt Test (HUTT) has been widely used for the past four decades as part of the overall assessment of the potential causes of collapse in patients with recurring transient loss of consciousness (TLOC) of unknown cause. The ability of a positive HUTT often to reproduce patient symptoms and illustrate to the patient that the physician is confident of the diagnosis have been major advances in clinical TLOC management. Tilt testing has been particularly important in understanding and diagnosing vasovagal syncope (VVS) and orthostatic hypotension. Despite HUTT having great clinical utility, different HUTT protocols and drug provocations result in different test yields. Limited HUTT reproducibility has led some researchers to criticize HUTT utility. As in most medical tests, limitations are part of the test. Herein, we provide a contemporary review of HUTT's utility in diagnosing and managing various TLOC disorders with intent to clarify its role in clinical practice.

To assess the effects of two different body positions on the cardiovascular autonomic profile during a single bout of exercise in patients with postural orthostatic tachycardia syndrome (POTS).

Thirteen patients with POTS and thirteen healthy controls (C) participated in the study. ECG, respiration, beat-by-beat arterial pressure and O2 consumption (VO2) were continuously recorded while on a cycle ergometer in supine and upright positions, before and during exercise (6 min, 50 Watts). Spectral analysis of RR intervals and systolic arterial pressure (SAP) variability provided indexes of cardiac sympathovagal interaction (LF/HF ratio), cardiac vagal modulation (HFRR, high-frequency component of RR variability, ~ 0.25 Hz), sympathetic vasomotor control (LFSAP, low-frequency component of SAP variability, 0.1 Hz) and baroreflex sensitivity (BRS, αLF).

While supine, patients with POTS showed lower HFRR and αLF, greater heart rate (HR), LF/HF and LFSAP, compared with C, suggesting cardiovascular sympathetic over-activity and reduced BRS. While sitting upright, POTS showed greater HR and reduced HFRR and αLF compared with C. During supine exercise, SAP, HR, LF/HF increased and HFRR and αLF decreased similarly in POTS and C. In POTS, upright sitting exercise was associated with slightly higherV ˙ O 2 , a greater increase in HR whereas LFSAP was lower than in C.

Upright exercise was associated with excessive enhancement of HR and a blunted increase of the sympathetic vasomotor control in POTS. Conversely, supine exercise-induced hemodynamic and autonomic changes similar in POTS and C, thus making supine exercise potentially more suitable for physical rehabilitation in POTS.

The aim of the study is to analyze and compare the cognitive profile between 59 patients with long-COVID [LC; 30 of them with and 29 without a positive coronavirus disease 2019 (COVID-19) confirmatory test] and 31 patients with postural orthostatic tachycardia syndrome (POTS) and a matched group of 39 healthy control participants.

Participants were examined on a battery of neuropsychological tests, including verbal memory, visuospatial abilities, attention, processing speed, verbal fluency, working memory, and visual memory. Anxious-depressive symptomatology was also analyzed and then controlled for possible influence on cognitive performance.

Patients with LC and POTS showed significantly lower performance compared with healthy peers. Differences on anxious and depressive symptoms were also found between the clinical and control groups, resulting in LC without a positive confirmatory test group exhibiting the highest rates of anxious symptoms. After controlling the effects of anxious-depressive symptomatology, the differences were eliminated for some of the cognitive variables, but additional differences were found between patients with LC and POTS after post hoc analysis.

Findings from the present study contribute toward the reinforcement of the evidence on cognitive alterations associated with LC and POTS. Anxious-depressive symptomatology has to be considered in both clinical groups since it could be affecting cognitive performance.

Postural Orthostatic Tachycardia Syndrome (POTS) is a form of cardiovascular autonomic disorders characterized by orthostatic intolerance and a symptomatic increase in heart rate upon standing, which can significantly impair patients' quality of life. Its pathophysiology is complex, multifactorial; thus, a variety of treatment approaches have been investigated. Recent studies have identified three primary POTS phenotypes-hyperadrenergic, neuropathic, and hypovolemic-each requiring tailored management strategies. First-line treatment for all patients focuses on lifestyle modifications, including increased fluid and salt intake, compression garment use, physical reconditioning, and postural training. Currently, there are no medications approved by the United States Food and Drug Administration (FDA)for POTS. Pharmacologic therapies are primarily used to manage specific symptoms, though the evidence supporting their efficacy is limited. In hyperadrenergic POTS, excessive norepinephrine production or impaired reuptake leads to sympathetic overactivity, making beta-blockers an effective option. Neuropathic POTS, resulting from impaired vasoconstriction during orthostatic stress, responds to agents that enhance vascular tone, such as pyridostigmine and midodrine. Hypovolemic POTS, often triggered by dehydration and physical deconditioning, respond primarily to volume expansion and exercise. This review article provides a comprehensive overview of the pathophysiology and management strategies for POTS, with a focus on phenotype-based approaches to guide tailored treatment and improve patient outcomes.

Orexins (OXs) are critical for regulating circadian rhythms, arousal, appetite, energy metabolism, and electrolyte balance, affecting both the autonomic nervous system (ANS) and the cardiovascular system (CVS). Disruption of the OX system can result in symptoms similar to those observed in post-acute sequelae of COVID-19 (PASC). This review emphasizes the adverse effects of OX dysregulation on autonomic and cardiometabolic functions in patients with PASC. Additionally, we highlight the potential of anti-OX therapies to provide neuroprotective, anti-inflammatory, and immunoregulatory benefits, offering hope for alleviating some of the debilitating symptoms associated with PASC.

Exercise is a well-documented, nonpharmacologic treatment for individuals with autonomic dysfunction and associated orthostatic intolerance, such as postural tachycardia syndrome and related disorders. Exercise has been shown to increase blood volume, reverse cardiovascular deconditioning, and improve quality of life. Current first-line standard of care treatment for autonomic dysfunction combines graded approaches to exercise with medications and lifestyle modifications. However, current exercise rehabilitation protocols for postural orthostatic tachycardia syndrome contain rigid timelines and progression paradigms that often threaten tolerability and adherence. In addition, they fail to account for clinical variables potentially critical to care and lack guidance for individualization, limiting accessibility to patients with co-morbidities that affect exercise appropriateness and safety. Therefore, we introduce an adaptive approach to exercise prescription for orthostatic intolerance that allows patient-specific modifications to meet functional goals for a wider spectrum of patients, thus improving adherence. The proposed approach integrates iterative physiological and symptomatic assessments to provide flexible, yet structured, exposure to aerobic exercise and strength training to improve functional capacity and tolerance of daily activities for patients with postural tachycardia syndrome and related autonomic disorders.

Orthostatic intolerance (OI) is a common problem. Reliable markers of OI are missing, as orthostatic blood pressure and heart rate poorly correlate with orthostatic symptoms. The objective of this study was to assess the relationship between orthostatic lightheadedness and cerebral blood flow. In this retrospective study patients with OI were evaluated at the Autonomic Laboratory of the Department of Neurology, Brigham and Women's Faulkner Hospital, Boston. The 10-minute head-up tilt test was performed as a part of autonomic testing. Orthostatic lightheadedness was evaluated at every minute of the head-up tilt. Heart rate, blood pressure, capnography, and cerebral blood flow velocity (CBFv) in the middle cerebral artery using transcranial Doppler were measured. Repeated-measures design with a linear mixed-effects model was used to evaluate the relationship between orthostatic lightheadedness and hemodynamic variables. Correlation analyses were done by calculating Pearson's coefficient. Twenty-two patients with OI were compared to nineteen controls. Orthostatic CBFv and end-tidal CO2 decreased in OI patients compared to controls (p < 0.001) and predicted orthostatic lightheadedness. Orthostatic heart rate and blood pressure failed to predict orthostatic lightheadedness. The lightheadedness threshold, which marked the onset of lightheadedness, was equal to an average systolic CBFv decrease of 18.92% and end-tidal CO2 of 12.82%. The intensity of lightheadedness was proportional to the CBFv and end-tidal CO2 decline. Orthostatic lightheadedness correlated with systolic CBFv (r=-0.6, p < 0.001) and end-tidal CO2 (r=-0.33, p < 0.001) decline. In conclusion, orthostatic CBFv and end-tidal CO2 changes predict orthostatic lightheadedness and can be used as objective markers of OI.

We delineated the association between otolithic dysfunction and blood pressure (BP) variability.

We prospectively recruited 145 consecutive patients (age=71 [59-79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBPSD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups.

A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBPSD (p=0.012), and female sex (p=0.004). SBPSD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1-p1 amplitude (p=0.491) or normalized p13-n23 amplitude (p=0.193) in patients with OH. The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBPSD, with an area under the receiver operating characteristic curve of 0.73.

Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions in Parkinson's disease (PD) patients. However, many patients with OH are asymptomatic. Conversely, orthostatic dizziness (OD) is not always associated with OH. We investigated the effects of positional changes on cerebral perfusion in patients with PD and OH.

We enrolled 42 patients, comprising 31 PD patients and 11 healthy controls. All the subjects underwent the following clinical assessments: the OH questionnaire, head-up tilt test (HUTT) with transcranial Doppler (TCD), near-infrared spectroscopy, measurement of the change in oxygenated hemoglobin (ΔHboxy) during the squat-to-stand test (SST), measurement of the time derivative of total hemoglobin (DHbtot), and time taken to reach the peak (peak time [PT]) of DHbtot after restanding.

The mean flow velocity change (ΔMFV) in the TCD during the HUTT failed to differentiate between the PD-OH(+) and PD-OH(-) groups. The change in oxygenated hemoglobin ΔHboxy was greater in the PD-OH(+) group, which persisted for 9 min until the end of the HUTT only in the left hemisphere. During SST, PT was significantly delayed in the left hemisphere in PD-OH(+) patients.

Although TCD demonstrated no significant difference in ΔMFV, the parameters measured by near-infrared spectroscopy, such as ΔHboxy during HUTT and PT during the SST, significantly increased ΔHboxy or delayed PT in the left hemisphere of PD-OH(+). Positional changes have a detrimental effect on cerebral hemodynamics in patients with PD and OH, especially in the left hemisphere.

There has been an increasingly reported association between Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS) and gastrointestinal disorders. EDS is a hereditary connective tissue disorder which may manifest as a spectrum of symptoms stemming from collagen defects. The prevalence of EDS is estimated to affect 1 in 5000 individuals which underscores its clinical significance. Notably the hypermobile form (hEDS) accounts for the majority of cases. POTS is characterized by orthostatic intolerance with an increase in heart rate on standing in the absence of hypotension. This condition predominantly affects women between 15 and 45 years of age. Gastrointestinal symptoms in the form of reflux, bloating and abdominal pain significant impact this population. Gastroparesis is a chronic disorder involving symptoms of delayed gastric emptying and may be closely associated with hEDS and POTS, and may be underreported. Autonomic dysfunction associated with hEDS has been proposed as the likely mechanism underlying POTS and gastrointestinal dysfunction though a clear pathophysiological process has not been established.

Postural Orthostatic Tachycardia Syndrome (POTS) affects up to 1% of the US population, predominantly women, and is characterized by a complex, elusive etiology and heterogeneous phenotypes. This review delves into the intricate physiology and etiology of POTS, decoding the roles of the sinoatrial node, the autonomic nervous system, fluid dynamics, and the interplay between the immune and endocrine systems. It further examines key contributing factors such as dysautonomia, thoracic hypovolemia, autonomic neuropathies, sympathetic denervation, autoimmune responses, and associations with conditions such as small-fiber neuropathy and mast cell activation syndrome. Given the numerous mysteries surrounding POTS, we also cautiously bring attention to sinoatrial node and myocardial function, particularly in how the heart responds to stress despite exhibiting a normal cardiac phenotype at rest. The potential of genomic research in elucidating the underlying mechanisms of POTS is emphasized, suggesting this as a valuable approach that is likely to improve our understanding of the genetic underpinnings of POTS. The review introduces a tentative classification system for the etiological factors in POTS, which seeks to capture the condition's diverse aspects by categorizing various etiological factors and acknowledging co-occurring conditions. This classification, while aiming to enhance understanding and optimize treatment targets, is presented as a preliminary model needing further study and refinement. This review underscores the ongoing need for research to unravel the complexities of POTS and to develop targeted therapies that can improve patient outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts between the host and virus and govern induction, resulting in multiorgan impacts. Its pathophysiology involves the followings: 1) the angiotensin-converting enzyme (ACE2) and Toll-like receptor (TLR) pathways: 2) the neuropilin (NRP) pathway: 3) the spike protein pathway. Therefore, it is necessary to block the pathological course with modulating innate lymphoid cells against diverse corona variants in the future.

Postural Orthostatic Tachycardia Syndrome (POTS) affects approximately 1% of adolescents, however, little research has been done in this area. This retrospective chart review describes the treatment goals and perceived progress as measured by the Canadian Occupational Performance Measure (COPM) of 111 adolescents and young adults (AYAs) aged 12-22 (M = 15.8, SD = 1.8) diagnosed with POTS who were admitted to an interdisciplinary intensive pain treatment program (IIPT). This study also examined the change in progress and satisfaction in goals over a 3-week intensive pain treatment program, as well as the utility and validity of the COPM as an outcome measure for AYAs attending an IIPT. Results indicated adolescents and young adults endorsed treatment goals focused on self-care, school, and leisure and found that performance and satisfaction scores significantly improved from admission to discharge. The findings also suggest that the COPM is a useful and valid outcome measure for this population.

Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID). PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction. Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature. In this review, we discuss the evidence implicating Borrelia burgdorferi as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.

Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood.

We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established.

POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of a variety of chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block the flow of blood through microcapillaries and thus cause tissue hypoxia, are not simply correlated with but in fact, by preceding it, may be a chief intermediary cause of POTS, in which tachycardia is simply the body's exaggerated 'physiological' response to hypoxia. Similar reasoning accounts for the symptoms bundled under the term 'fatigue'. Amyloids are known to be membrane disruptors, and when their targets are nerve membranes, this can explain neurotoxicity and hence the autonomic nervous system dysfunction that contributes to POTS. Taken together as a system view, we indicate that fibrinaloid microclots can serve to link POTS and fatigue in long COVID in a manner that is at once both mechanistic and explanatory. This has clear implications for the treatment of such diseases.

Gastrointestinal (GI) symptoms are common in postural orthostatic tachycardia syndrome (POTS). We aimed to explore the prevalence and severity of GI symptoms in POTS, and to investigate immunological factors, hemodynamic findings, and their possible association with GI symptoms in POTS. Forty-three patients (93% female, median age 30.6 (26.0-41.0) years), previously diagnosed with POTS and 74 healthy controls (78% female, median age 35.6 (28.8-41.7) years) were included. The participants completed a questionnaire including prevalence of GI symptoms, the irritable bowel syndrome severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). All POTS patients were previously examined by tilt test (2010-2021) and the vast majority with more recent active standing test (2017-2021), which included monitoring of heart rate (HR). ΔHR was calculated as difference between supine and upright position. Continuous variables from IBS-SSS and VAS-IBS were correlated to ΔHR. A microarray containing several autoantigens commonly targeted in systemic autoimmune disorders was used to assess prevalent autoantibodies in POTS and controls. Total IgE and S-tryptase were analyzed. GI symptoms were more prevalent and severe in POTS than in controls; nausea being the most prevalent (79.1% vs 4.9%, p < 0.001) and bloating and flatulence being the most severe (median 65 (25-88) vs 0 (0-14), p < 0.001). The median total IBS-SSS was 213 (135-319) in POTS vs 13 (0-54) in controls (p < 0.001). Total IBS-SSS was associated with low psychological wellbeing (r = 0.539, p < 0.001) in POTS. ΔHRmax correlated inversely with abdominal pain (r = -0.406, p = 0.007). After adjustments for psychological wellbeing, total IBS-SSS still associated inversely with ΔHR10min (β: 4.748; 95% CI: -9.172 to -0.324; p = 0.036). Similar results were seen with active standing test. The prevalence of autoantibodies did not differ between POTS and controls (29.4% vs 33.3%, p = 0.803). There was no association between GI symptoms and autoantibody status. Total IgE and tryptase were elevated in a few cases. This study confirms the high prevalence of GI symptoms in POTS. More pronounced tachycardia upon tilt table testing seems to be inversely correlated with severity of chronic GI symptoms in POTS. This study did not support the hypothesis that POTS is associated with immunological factors.

Kidney damage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur even in patients with no underlying kidney disease. Signs of kidney problems can progress to a state that demands dialysis and hampering recovery. Although not without controversy, emerging evidence implicates direct infectivity of SARS-CoV-2 in the kidney. At the early stage of the pandemic, consideration was mainly on the well-recognized angiotensin-converting enzyme 2 (ACE2) receptor as being the site for viral interaction and subsequent cellular internalization. Despite the abundance of ACE2 receptors in the kidneys, researchers have expanded beyond ACE2 and identified novel viral entry pathways that could be advantageously explored as therapeutic targets. This review presents the potential involvement of toll-like receptor 4 (TLR-4), kidney injury molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1), and cluster of differentiation 147 (CD147) in SARS-CoV-2-associated renal damage. In this context, we address the unresolved issues surrounding SARS-CoV-2 renal infectivity.

Postural orthostatic tachycardia syndrome (POTS) presents heterogeneously and is diagnosed when appropriate symptoms are present in conjunction with a heart rate increase of at least 30 beats-per-minute upon standing without orthostatic hypotension. Much of the current understanding of POTS is based on clinical expertise, particularly regarding POTS phenotypes and their potential role in targeting pharmacologic treatment. This study describes the symptom presentation of POTS by phenotypes at a subspecialty POTS clinic. Data was collected prospectively during clinical visits between April 17, 2014 and February 8, 2021. This data was abstracted retrospectively by chart review. Most of the 378 study participants were female (89.9%) with a mean age 23.0 ± 4.9 years. Lightheadedness was the most common (97.6%) symptom and the most disruptive of quality of life (29.9%). Patients reported substantial functional impairment across multiple life domains, with 3.0 ± 2.8 days lost and 4.7 ± 2.3 unproductive days per week. There were no differences in symptom presentation among POTS phenotypes. POTS phenotypes are not distinguishable based on symptoms alone; if phenotyping is sought, testing is necessary. Further research is needed in better classifying POTS phenotypes with the potential goal of tailoring treatment.

Background and Objectives: During tilt testing, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients experience an abnormal reduction in cerebral blood flow (CBF). The relationship between this CBF reduction and symptom severity has not been examined in detail. Our hypothesis was that ME/CFS severity is related to the degree of the CBF reduction during tilt testing. Materials and Methods: First, from our database, we selected ME/CFS patients who had undergone assessments of ME/CFS symptomatology and tilt tests on the same day, one at the first visit and the second during a follow-up. The change in symptomatology was related to the change in CBF during the tilt test. Second, we combined the data of two previously published studies (n = 219), where disease severity as defined by the 2011 international consensus criteria (ICC) was available but not published. Results: 71 patients were retested because of worsening symptoms. The ICC disease severity distribution (mild-moderate-severe) changed from 51/45/4% at visit-1 to 1/72/27% at follow-up (p < 0.0001). The %CBF reduction changed from initially 19% to 31% at follow-up (p < 0.0001). Of 39 patients with stable disease, the severity distribution was similar at visit-1 (36/51/13%) and at follow-up (33/49/18%), p = ns. The %CBF reduction remained unchanged: both 24%, p = ns. The combined data of the two previously published studies showed that patients with mild, moderate, and severe disease had %CBF reductions of 25, 29, and 33%, respectively (p < 0.0001). Conclusions: Disease severity and %CBF reduction during tilt testing are highly associated in ME/CFS: a more severe disease is related to a larger %CBF reduction. The data suggest a causal relationship where a larger CBF reduction leads to worsening symptoms.

Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC).

Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions.

The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09).

Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.

Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning.

The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains.

We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI.

This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Dysautonomia refers to the dysfunction of the autonomic nervous system and encompasses a wide variety of autonomic symptoms and disorders. The most common autonomic disorders are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be encountered in clinical practice as part of a triad of dysautonomia, hypermobility spectrum disorders (HSD), and mast cell activation syndrome (MCAS). Migraine is one of the most common comorbidities of POTS, HSD, and MCAS; conversely, these conditions are also prevalent in patients with migraine, especially in those with multiple systemic symptoms, such as chronic dizziness, lightheadedness, orthostatic intolerance, joint pain, and allergic symptoms. Diagnostic criteria, pathophysiologic mechanisms, and therapeutic considerations in patients with migraine and comorbid dysautonomia, HSD, and MCAS are reviewed.

Numerous studies indicate a significant overlap and shared pathophysiology in migraine, dysautonomia, HSD, and MCAS. In clinical setting, dysautonomia, HSD, and MCAS may present a diagnostic and therapeutic challenge in patients with migraine and require a high index of suspicion on the part of the neurologist. Diagnosis and treatment of these complex disorders in patients with migraine is essential to comprehensive patient-centric care, reduced symptom burden, and improved functional impairment secondary to both migraine and comorbidities.

Postural tachycardia syndrome (POTS) is associated with complaints of cognitive and emotional difficulties that may contribute to severe functional disability. For high-achieving adolescents, these symptoms can result in decreased participation in school and extracurricular activities. There are very limited data comparing subjective symptom reports to neurocognitive profiles in adolescents presenting with POTS, "brain fog," and cognitive difficulties.

A review of medical records and neuropsychological data was conducted for six adolescents diagnosed with POTS at a pediatric neurology clinic. All patients had frequent symptoms of orthostatic intolerance for more than three months. There was heart rate increase of ≥40 beats per minute (bpm) within 10 minutes of active standing or head-up tilt test in five patients and 36 bpm in one patient, who was diagnosed with probable POTS. All were referred for neuropsychological evaluations due to reported debilitating cognitive problems and an inability to function in a regular academic setting. Patients underwent a six-hour neuropsychological evaluation utilizing standardized measures of cognitive and emotional functioning. Clinically reported symptoms included fatigue, poor concentration, and memory impairment as well as "brain fog."

Subjective complaints differed from patients' performance on standardized neuropsychological measures. Patients performed in the average to superior range across measures of general intelligence, verbal and working memory, processing speed, and sustained attention.

Further research is needed to elucidate the basis for perceived "brain fog" and cognitive impairment in POTS, such as better understanding of patient and parental perceptions of initial medical symptoms and diagnosis as well as symptom amplification due to biopsychosocial processes.

To delineate the association between otolith function and changes in mean orthostatic blood pressure (BP) and heart rate (HR) in patients with postural orthostatic tachycardia syndrome (POTS).

Forty-nine patients with POTS were prospectively recruited. We analyzed the results of ocular vestibular-evoked myogenic potentials (oVEMPs) and cervical vestibular-evoked myogenic potentials (cVEMPs), as well as head-up tilt table tests using a Finometer. The oVEMP and cVEMP responses were obtained using tapping stimuli and 110 dB tone-burst sounds, respectively. We measured maximal changes in 5-s averaged systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) within 15 s and during 10 min after tilting. We compared the results with those of 20 age- and sex-matched healthy participants.

The n1-p1 amplitude of oVEMPs was larger in patients with POTS than in healthy participants (p = 0.001), whereas the n1 latency (p = 0.280) and interaural difference (p = 0.199) did not differ between the two. The n1-p1 amplitude was a positive predictor for POTS (odds ratio 1.07, 95% confidence interval 1.01-1.13, p = 0.025). Body weight (p = 0.007) and n1-p1 amplitude of oVEMP (p = 0.019) were positive predictors for ΔSBP15s in POTS, whereas aging was a negative predictor (p = 0.005). These findings were not observed in healthy participants.

Augmented utricular inputs may be associated with a relative predominance of sympathetic over vagal control of BP and HR, especially for an early response during orthostasis in patients with POTS. Overt sympathoexcitation due to exaggerated utricular input and lack of readaptation may be associated with the pathomechanism of POTS.

The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID. These associated illnesses, whose patients are 70%-80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause. We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

POTS (Postural Orthostatic Tachycardia Syndrome) is a multisystem disorder characterized by the abnormal autonomic response to an upright posture, causing orthostatic intolerance and excessive tachycardia without hypotension. Recent reports suggest that a significant percentage of COVID-19 survivors develop POTS within 6 to 8 months of infection. Prominent symptoms of POTS include fatigue, orthostatic intolerance, tachycardia, and cognitive impairment. The exact mechanisms of post-COVID-19 POTS are unclear. Still, different hypotheses have been given, including autoantibody production against autonomic nerve fibers, direct toxic effects of SARS-CoV-2, or sympathetic nervous system stimulation secondary to infection. Physicians should have a high suspicion of POTS in COVID-19 survival when presented with symptoms of autonomic dysfunction and should conduct diagnostic tests like the Tilt table and others to confirm it. The management of COVID-19-related POTS requires a comprehensive approach. Most patients respond to initial non-pharmacological options, but when the symptoms become more severe and they do not respond to the non-pharmacological approach, pharmacological options are considered. We have limited understanding and knowledge of post-COVID-19 POTS, and further research is warranted to improve our understanding and formulate a better management plan.

Previous studies demonstrated M2 muscarinic acetylcholine receptor-activating autoantibodies (M2R-AAb) were present in some patients with postural tachycardia syndrome (POTS). This study examines how these autoantibodies might contribute to the pathophysiology of POTS, and whether low-level tragus stimulation (LLTS) can ameliorate autoantibody-mediated autonomic dysregulation in the rabbit.

Five New Zealand white rabbits were immunized with a M2R second extracellular loop peptide to produce cholinomimetic M2R-AAb. Tilt test and infusion studies were performed on conscious rabbits before immunization, 6 weeks after immunization, and 8 weeks after immunization with 2-week daily LLTS treatment. Each rabbit served as its own control.

Compared to preimmune state, an enhanced heart rate increase and decreased parasympathetic activity upon tilting were observed in immunized rabbits. Furthermore, these rabbits demonstrated an attenuated heart rate-slowing response to infusion of the M2R orthosteric agonist arecaidine propargyl ester (APE), suggesting an inhibitory allosteric effect of M2R-AAb. There was also a significant increase in serum inflammatory cytokines in immunized rabbits. LLTS treatment suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, reduced the levels of inflammatory cytokines, and reversed the attenuated heart rate response to APE in immunized rabbits. No suppression of M2R-AAb expression by LLTS was found during this short-term study period. Receptor-modulating activity of M2R-AAb produced in immunized rabbits was confirmed with in vitro bioassay.

Autoantibody inhibition of cholinergic ligand activity may be involved in the development of cardiovagal dysfunction and inflammation associated with POTS, both of which can be improved by vagal stimulation.

There is sparse literature on cardiac arrhythmias and the utility of ambulatory rhythm monitoring in patients with postural tachycardia syndrome and orthostatic intolerance. This study's primary aim was to investigate the prevalence of arrhythmias in this population. Knowing the prevalence and types of arrhythmias in dysautonomia patients could influence the decision to pursue ambulatory rhythm monitoring and ultimately guide therapy.

This retrospective descriptive study examined the frequency of cardiac arrhythmias, as detected by ambulatory rhythm monitoring, in children with postural tachycardia syndrome/orthostatic intolerance or syncope who were seen at the Children's National Hospital Electrophysiology Clinic between January 2001 and December 2020.

In postural tachycardia syndrome/orthostatic intolerance patients, arrhythmia was detected on 15% of 332 ambulatory rhythm monitors. In syncope patients, arrhythmia was detected on 16% of 157 ambulatory rhythm monitors, not significantly different from the postural tachycardia syndrome/orthostatic intolerance group. The difference in rate of arrhythmia detection between 24-hour Holter and 2-week Zio® monitoring was not statistically significant.

This study suggests that a substantial proportion of postural tachycardia syndrome/orthostatic intolerance patients may have concomitant underlying cardiac arrhythmias, at a frequency similar to what is seen in patients undergoing primary evaluation for cardiac symptoms such as chest pain, palpitations, and syncope. In the appropriate clinical context, physicians caring for postural tachycardia syndrome/orthostatic intolerance patients should consider additional evaluation for arrhythmias beyond sinus tachycardia.

Postural Orthostatic Tachycardia Syndrome (POTS) is a rare disorder of the autonomic nervous system. The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. This case report is about a patient with post-viral neuropathic POTS. Neuropathic POTS is believed to be due to the damage of small nerve fibers that regulate the constriction of the blood vessels in the limb and abdomen, which leads to interference with vasoconstriction, and therefore causes tachycardia. Current literature emphasizes a treatment that is based on lifestyle modifications, such as increasing water and salt intake, and symptomatic pharmacological treatment. In this case, the 39-year-old male ptient was treated with osteopathic manipulative treatment (OMT), specifically the compression of the fourth ventricle (CV4), which has been associated with the production of hyperparasympathetic and anti-inflammatory effects and, hence, helps overcome the small-fiber neuropathy caused by the viral illness. We found that the CV4 technique led to the successful remission of the patient's symptoms. Therefore, we propose craniosacral therapy as a successful single management modality in patients with POTS.

An increase in post-COVID patients with late sequelae of acute COVID-19 infection is emerging as an ongoing challenge for physicians and healthcare professionals. Since the beginning of the pandemic, it has rapidly become evident that the acute infection is not limited to the respiratory tract but that several organs, including the cardiovascular system, can be affected. Moreover, in a significant proportion of patients (ranging from about 10 to up to 50%) with former COVID-19, cardiopulmonary symptoms such as dyspnea, palpitations, restricted physical capacity, and cardiac arrhythmias can persist weeks and months after the acute SARS-CoV-2 infection. The spectrum of COVID-19-associated arrhythmias is rather wide, most likely due to various pathomechanisms. In this article, the prevalence of cardiac arrhythmias and underlying pathologies are reviewed, including direct myocardial injury and abnormal consequences with an impact on cardiac electric instability. The hyperinflammatory reaction of the host immune system is specifically considered. Moreover, several distinct rhythm disorders occurring in post-COVID patients are discussed with regard to their clinical management.

To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH).

Young, healthy women were recruited, including OC users (n = 12) and non-users (NOC; n = 9). Women were tested during the low hormone (LH; placebo pills; days 2-5 natural cycle) and high hormone (HH; active dose; days 18-24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30 s of standing were examined.

There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCA_V) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCA_V (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle.

Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.

To delineate the association between otolithic dysfunction and orthostatic hypotension (OH).

We retrospectively reviewed the medical records of 382 patients who presented with orthostatic dizziness at a tertiary dizziness center between July 2017 and December 2021. Patients were included for analyses when they had completed ocular (oVEMP) and/or cervical vestibular-evoked myogenic potentials (cVEMP), and head-up tilt table test with a Finometer (n = 155). We compared the results between the patients with OH (n = 38) and those with NOI (normal head-up tilt table test despite orthostatic intolerance, n = 117).

Thirty-eight patients with OH were further categorized as either classic (n = 30), delayed (n = 7), or initial (n = 1) types. Multivariable logistic regression showed that OH was associated with high baseline systolic BP (p = 0.046), presence of heart failure (p = 0.016), and unilateral oVEMP abnormalities (p = 0.016). n1 latency of oVEMP were negatively correlated with the maximal changes of systolic blood pressure (BP) in 15 s ([Formula: see text]SBP_15s, p = 0.013), 3 min ([Formula: see text]SBP_3min, p = 0.005) and 10 min ([Formula: see text]SBP_10min, p = 0.002). In contrast, the n1-p1 amplitude was positively correlated with [Formula: see text]SBP_15s (p = 0.029). Meanwhile, p13 latency of cVEMP was negatively correlated with [Formula: see text]SBP_10min (p = 0.018).

Our study provides evidence of utricular dysfunction related to OH.

Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.

To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.

Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.

2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.

The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.

Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].

Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies.

In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic.

Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.