Randomized controlled trial of intravenous immunoglobulin for autoimmune postural orthostatic tachycardia syndrome (iSTAND).

OBJECTIVE: This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS). BACKGROUND: POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted. METHODS: This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion. RESULTS: A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups. CONCLUSIONS: This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.

Postural Orthostatic Tachycardia Syndrome Associated with COVID-19: A Narrative Review.

Postural orthostatic tachycardia syndrome (POTS) is a complex condition marked by an atypical autonomic response to standing, leading to orthostatic intolerance and significant tachycardia without accompanying hypotension. In recent studies, a considerable number of individuals recovering from COVID-19 have been reported to experience POTS within 6 to 8 months post-infection. Key symptoms of POTS include fatigue, difficulty with orthostatic tolerance, tachycardia, and cognitive challenges. The underlying causes of POTS following COVID-19 remain unknown, with various theories proposed such as renin-angiotensin-aldosterone system (RAAS) dysregulation, hyperadrenergic reaction, and direct viral infection. Healthcare professionals should be vigilant for POTS in patients who have recovered from COVID-19 and are experiencing signs of autonomic dysfunction and use diagnostic procedures such as the tilt-up table test for confirmation. COVID-19-related POTS should be approached with a holistic strategy. Although many patients show improvement with initial non-drug treatments, for subjects who do not respond and exhibit more severe symptoms, medication-based therapies may be necessary. The current understanding of COVID-19-related POTS is limited, underscoring the need for more research to increase knowledge and enhance treatment approaches.

Dysautonomia, Hypermobility Spectrum Disorders and Mast Cell Activation Syndrome as Migraine Comorbidities.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study).

PURPOSE: Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing. METHODS: In this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions. RESULTS: Patients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing. CONCLUSION: Compared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS. TRIAL REGISTRATION INFORMATION: The study was registered at ClinicalTrials.gov (NCT03681080).

Severe Post-COVID-19 dysautonomia: a case report.

BACKGROUND: The emergence of dysautonomia as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; or COVID-19) is becoming more prevalent. We have seen evidence in several post-COVID patients and in the literature of varying degrees of autonomic dysfunction. Symptoms, among others, include inappropriate tachycardia, sweating, anxiety, insomnia and blood pressure variability from the effects of excessive catecholamine, as well as cognitive impairment, fatigue, headaches and orthostatic intolerance from decreased brain perfusion. CASE PRESENTATION: We present a case of severe dysautonomia in a previously healthy 27-year-old runner. About five weeks after her initial mild COVID-19 infection, the patient began to develop weakness, which progressed into severe post-exertional fatigue, slowed cognition, headaches, blurred vision and generalized body aches. She also endorsed palpitations, especially when getting up from a seated or lying position as well as with mild exertion. She became reliant on her husband for help with her activities of daily living. Exam was significant for orthostasis; laboratory workup unremarkable. Over the following months, the patient's symptoms have improved slowly with fluid and sodium intake, compression stockings and participating in a graduated exercise program. CONCLUSIONS: Dysautonomia as a consequence of infection with COVID-19 is becoming increasingly discussed, especially as more patients recover from COVID-19. This is a case of a non-hospitalized patient with a mild initial presentation and significant, debilitating dysautonomia symptoms. More research on its pathophysiology, especially in relation to a precedent viral insult, as well as its treatment, is needed.

Regional Gastrointestinal Transit and Contractility Patterns Vary in Postural Orthostatic Tachycardia Syndrome (POTS).

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that affects multiple organs, including the gastrointestinal system. These patients often have multiple GI complaints with a severe impact on their quality of life. GI dysmotility patterns in POTS remains poorly understood and difficult to manage. AIMS: The aim of this study was to investigate the diagnostic yield of wireless motility capsule in patients with gastrointestinal symptoms and POTS, with use of a symptomatic control group without POTS as a reference. METHODS: We retrospectively reviewed the charts of patients who had both autonomic testing and wireless motility capsule between 2016 and 2020. The two groups were divided into those with POTS and those without POTS (controls) as diagnosed through autonomic testing. We compared the regional transit times and motility patterns between the two groups using the data collected from wireless motility capsule. RESULTS: A total of 25% of POTS patients had delayed small bowel transit compared to 0% of non-POTS patients (p = 0.047). POTS patients exhibited hypo-contractility patterns within the small bowel, including decreased contractions/min (2.95 vs. 4.22, p = 0.011) and decreased motility index (101.36 vs. 182.11, p = 0.021). In multivariable linear regression analysis, migraine predicted faster small bowel transit (p = 0.007) and presence of POTS predicted slower small bowel transit (p = 0.044). CONCLUSIONS: Motility abnormalities among POTS patients seem to affect mostly the small bowel and exhibit a general hypo-contractility pattern. Wireless motility capsule can be a helpful tool in patients with POTS and GI symptoms as it can potentially help guide treatment.

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

Neurocognitive Difficulties Among Youth with POTS within an Intensive Pain Rehabilitation Program.

OBJECTIVE: Adolescents and young adults (AYAs) with postural orthostatic tachycardia syndrome (POTS) commonly report cognitive difficulties, though there is limited information regarding the objective measurement of neurocognitive deficits in this population. This study described the rates of subjectively experienced and objectively measured neurocognitive difficulties and explored effects of medications on neurocognitive functioning among AYAs with POTS admitted to an intensive outpatient pain rehabilitation program. METHODS: Participants in a pain rehabilitation program diagnosed with POTS (N = 96; ages 12-22) were included in the study. Medical characteristics, reported cognitive complaints, and neurocognitive assessment results were collected through retrospective medical record review. We calculated descriptive statistics and Pearson's χ2 or Fisher's exact tests, where appropriate. RESULTS: While 96% of this sample reported subjective cognitive complaints, as a group, they performed in the Average range on standardized measures of intellectual functioning, attention, and memory. The majority did not demonstrate any normative (73%) or relative (54%) weaknesses in attention or memory. Those prescribed an antiepileptic (n = 19) were less likely to have visual-spatial memory weaknesses but more likely to have attention weaknesses. CONCLUSIONS: Despite a high frequency of reported cognitive difficulties, most AYAs with POTS did not demonstrate neurocognitive impairment on standardized, one-on-one assessment. Suggestions for further study of biopsychosocial contributors to neurocognitive difficulties and for clinical use of neurocognitive assessments in this population were provided.

Postural Orthostatic Tachycardia Syndrome (POTS)--A novel member of the autoimmune family.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system in which a change from the supine position to an upright position causes an abnormally large increase in heart rate or tachycardia (30 bpm within 10 min of standing or head-up tilt). This response is accompanied by a decrease in blood flow to the brain and hence a spectrum of symptoms associated with cerebral hypoperfusion. Many of these POTS-related symptoms are also observed in chronic anxiety and panic disorders, and therefore POTS is frequently under- and misdiagnosed.

Sexual Dysfunction in Postural Orthostatic Tachycardia Syndrome (POTS): A Cross-Sectional, Case-Control Study.

Background: We aimed to determine whether patients with postural orthostatic tachycardia syndrome (POTS) have sexual dysfunction compared to age-matched healthy controls. Methods: Utilizing online COMPASS-31 to evaluate dysautonomia symptom severity, Beck's Depression Inventory Second Edition (BDII), Female Sexual Function (FSF), and International Index of Erection Function (IIEF) questionnaires, we compared sexual function scores in patients with POTS to scores obtained from sex- and age-matched healthy controls via a cross-sectional case-control study. Results: A total of 160 women with POTS, mean age 30.2 ± 7.9 (range 21-50 years), had lower FSF scores than 62 healthy age-matched female controls. IIEF scores in 29 male patients with POTS with a mean age of 30.1 ± 6.0 (range 21-47) were significantly lower than in 27 healthy age-matched male controls. Female POTS patients had significantly lower scores in the sub-domains of desire, arousal, and satisfaction, while male POTS patients had significantly lower scores in erectile and orgasmic function, desire, and satisfaction than healthy controls. Predictive factors of sexual dysfunction were depression in women and age in men. The severity of autonomic symptoms correlated with sexual dysfunction in women, but this effect disappeared after controlling for depression. Conclusions: Compared to healthy controls, women and men with POTS have significant sexual dysfunction, which needs to be considered in the diagnostic and therapeutic approaches as part of comprehensive patient care.

Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID.

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.

Median Arcuate Ligament Syndrome in Children: A Single-Center Experience.

BACKGROUND: Data on median arcuate ligament syndrome (MALS) in children are scant. It is postulated that MALS can cause chronic abdominal pain. It is unclear what percentage of children with this condition are symptomatic and what comorbidities are associated with this syndrome. METHODS: In this retrospective study, data on consecutive patients in a single center diagnosed coincidentally with MALS during routine echocardiogram were reviewed. Symptom burden, comorbidities, and the effect of anthropometric indices on MALS were investigated. Descriptive statistics and nonparametric tests were used to describe the findings and to compare variables with normal distribution. RESULTS: Between 2013 and 2020, there were 82 children, 55 females (67%), mean age 13.9 ± 3.2 years, with MALS and complete record. Mean velocity across the stenotic area was 2.6 ± 0.4 m/s. Forty-six patients (57%) had abdominal pain. Age, gender, weight, body mass index (BMI), and Doppler velocity had no statistically significant influence on symptom occurrence. Conversely, patients with joint hypermobility and symptoms of orthostatic intolerance were more likely to have abdominal pain from MALS. Of 24 patients with joint hypermobility, 18 patients had abdominal pain (p=0.027). Thirty-eight patients with orthostatic intolerance (OI) with MALS complained of abdominal pain vs 13 patients with OI and no abdominal pain (p=<0.0001). CONCLUSION: Nearly half of patients with MALS had abdominal pain. Age, gender, weight, and the degree of stenosis had no statistically significant influence on symptom occurrence. OI, specifically postural orthostatic tachycardia syndrome (POTS), and joint hypermobility on exam predicted a higher propensity for abdominal pain in patients with MALS.

Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?

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.

Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID.

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

Gut microbiota composition is altered in postural orthostatic tachycardia syndrome and post-acute COVID-19 syndrome.

Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.

Left Common Iliac Vein Stenting in a Case of Postural Orthostatic Tachycardia Syndrome/Pelvic Pain Overlap.

Postural orthostatic tachycardia syndrome (POTS) is mainly characterized by orthostatic intolerance and positional tachycardia although it frequently involves a myriad of non-specific symptoms that seem to overlap with existing medical conditions. Recent efforts have been made to further classify subtypes of POTS and associated conditions to better delineate underlying pathophysiology in an effort to guide diagnosis and tailor treatment. Here, we present a 22-year-old female with debilitating symptoms of POTS who reported pelvic pain on review of systems and underwent vascular ultrasound of the inferior vena cava, iliac veins, and bilateral lower extremities which revealed the characteristic left common iliac vein compression of May-Thurner syndrome prompting venous stenting which provided systemic symptomatic relief.

The Prevalence of Anxiety and Depression in Children With Postural Orthostatic Tachycardia Syndrome (POTS): A Retrospective Study.

INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance characterized by various symptoms such as dizziness, lightheadedness, and increased heart rate. Conflicting reports exist regarding the prevalence of anxiety and depression in adults with POTS, while data on pediatric POTS remains scarce. METHOD: A retrospective analysis of pediatric patients aged 11-17 years with POTS, who underwent autonomic testing at Nemours Children's Hospital in Orlando, Florida, was conducted. The patients were screened for anxiety, using the Severity Measure for Generalized Anxiety Disorder-Child Age 11-17 years (GAD-7) questionnaire, and depression, using PHQ-9 Modified for Adolescence (PHQ-A) for depression. The prevalence rates of anxiety and depression in the study cohort were compared to historical data from similar age groups in the existing literature. The study was approved by the Nemours Children's Hospital Institutional Review Board. RESULTS: The cohort comprised 27 children with POTS (26 females, age 15.8±1.6 years). Overall, 74% exhibited moderate-to-severe anxiety, depression, or both, with 44% having comorbid anxiety and depression. In total, 4/27 (14%) had pure depression and 4/27 (14%) had pure anxiety. Six patients had no depression or anxiety. On average, POTS symptoms began 1.9±1.3 years before diagnosis. Eleven patients took stable doses of psychotropic medications. After a follow-up period of 5.1±1.7 months of POTS therapy, seven patients had follow-up questionnaires. In 4/7 patients, the depression severity improved, and in 3/7 patients, the anxiety severity improved. Patients were not actively treated for depression and anxiety during this time. CONCLUSION: Anxiety and depression are prevalent among pediatric patients with POTS. While preliminary data suggests POTS therapy may alleviate these psychological symptoms, further longitudinal studies are warranted to explore the therapeutic impact in greater detail.

Suspected Diphtheria Toxoid and Tetanus Toxoid (dTdap) Booster Vaccine-Induced Postural Orthostatic Tachycardia Syndrome (POTS).

We describe a case of a 40-year-old South Asian woman who presented with symptoms suggestive of postural orthostatic tachycardia syndrome (POTS) following a diphtheria toxoid and tetanus toxoid (dTdap) booster vaccination administered one week prior. The patient's POTS responded favorably to treatment with low-dose fludrocortisone and ivabradine. Clinicians should maintain a high index of suspicion for POTS as a possible vaccine adverse event (VAE) post-dTdap booster inoculation and be aware of appropriate management strategies.

G protein-coupled receptors related to autoimmunity in postural orthostatic tachycardia syndrome.

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.

Evidence for Impaired Renin Activity in Postural Orthostatic Tachycardia Syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive symptom diversity implies multi-organ involvement that interacts in ways still requiring full exploration. Current understanding of POTS pathophysiology suggests alterations in the renin-angiotensin-aldosterone system as a possible contributing factor. Therefore, we investigated the relationship between the activity of the renin-angiotensin-aldosterone system and hemodynamic parameters in a cohort of POTS patients and controls recruited at a tertiary referral center. METHODS: The case-control study included 46 patients with POTS (27 ± 9 years), and 48 healthy controls (30 ± 9 years) without orthostatic intolerance. Plasma renin activity, expressed as angiotensin I generation, and plasma aldosterone were measured by enzyme-linked immunosorbent assay and were correlated with hemodynamic parameters obtained during active standing tests. RESULTS: Renin activity was significantly downregulated in POTS patients compared to healthy individuals (median, 3406 ng/mL vs. 9949 ng/mL, p < 0.001), whereas aldosterone concentration did not differ between POTS and healthy controls (median, 218 pmol/L vs. 218 pmol/L, p = 0.26). A significant inverse correlation between renin activity and supine and orthostatic blood pressure levels was observed in healthy individuals (p < 0.05 for all), but not in POTS patients. CONCLUSIONS: Renin activity, but not aldosterone concentration, is downregulated in patients with POTS. Moreover, renin activity in POTS is dissociated from supine and standing blood pressure levels in contrast to healthy individuals. These findings suggest impaired renin function in POTS, which may direct future therapeutic approaches.