Postural orthostatic tachycardia syndrome (POTS) is a poorly understood chronic disorder characterized by an unexplained excessive increase in heartbeat upon standing. The aim of this study was to investigate psychosocial and physiological correlates and predictors of symptom severity over time in patients presenting with POTS-like symptoms. Longitudinal cohort study of patients under investigation for POTS ( n = 149). Patients completed questionnaires at 1 month preclinic appointment and 6 months later. Diagnosis, blood pressure (BP), and heart rate (HR) measures were collected from medical records. Data were analyzed using hierarchical linear multiple regression. Orthostatic and small fiber neuropathy (SFN) symptoms remained stable over time and were significantly correlated with distress, cardiac anxiety, threatening views of the illness, and cognitive-behavioral responses to symptoms, but not with emotional reactivity or social support. Baseline psychosocial factors collectively explained 48% ( F = 5.37, p < .001) of the variance in orthostatic symptoms, and 35% ( F = 3.49, p < .001) of the variance of SFN symptoms at baseline, but a nonsignificant amount of variance in symptoms at 6 months when controlling for baseline symptoms. Hemodynamic measures explained a significant 4% ( F = 3.37, p = .026) of variance of orthostatic symptoms at 6 months. Symptom burden in patients with suspected POTS remained high over 6 months. Psychosocial factors explained a large amount of the variance in symptoms at baseline. As symptoms did not change/improve over time, baseline symptoms accounted for most of the variance in symptoms at 6 months. An integrated approach addressing psychosocial factors alongside medical treatments may promote adjustment to the condition and lessen symptom burden for this group.

Neurologic complications of long COVID-19 syndrome are one of the leading causes of global disability. In particular, post-COVID-19 cognitive dysfunction and dysautonomia in the form of postural orthostatic tachycardia syndrome (POTS) markedly affect patient quality of life and ability to return to work. The underlying pathophysiology of post-COVID-19 neurologic complications is unknown but is likely multifactorial with immune dysregulation and microvascular dysfunction playing central roles. Specific pathogenic factors with supportive evidence to date include cytokine-mediated inflammation, autoantibodies, immune exhaustion, disruption of the renin-angiotensin system, reduced serotonin levels, and microglial activation. The prevalence of post-COVID-19 cognitive dysfunction ranges from 10% to 88% and is affected by viral variant and hospitalization status among other factors, whereas that of long COVID-19 POTS is unknown due to referral bias and varying definitions. Treatment is largely supportive and often incorporates combined modalities. Marginal benefits with cognitive behavioral therapy, hyperbaric oxygen therapy, and supplements have been found for post-COVID-19 brain fog, whereas established POTS therapies aimed at improving venous return and reducing heart rate may reduce symptoms of long COVID-19 POTS. Although significant recovery has been noted for many cases of post-COVID-19 brain fog and POTS, prospective studies have revealed evidence of persistent symptoms and neurologic deficits a year after infection in some patients. Further studies that provide insight into the underlying pathophysiology of long COVID-19 are needed for development of target directed therapy.

A subset of patients with postural tachycardia syndrome (POTS) are thought to have a primary hyperadrenergic cause. We assessed clinical biomarkers to identify those that would benefit from sympatholytic therapy. We measured sympathetic function (supine muscle sympathetic nerve activity, upright plasma norepinephrine, and blood pressure responses to the Valsalva maneuver) in 28 patients with POTS (phenotyping cohort) to identify clinical biomarkers that are associated with responsiveness to the central sympatholytic guanfacine in a separate uncontrolled treatment cohort of 38 patients that had received guanfacine clinically for suspected hyperadrenergic POTS (HyperPOTS). In the phenotyping cohort, an increase in diastolic blood pressure (DBP) >17 mm Hg during late phase 2 of the Valsalva maneuver identified patients with the highest quartile of resting muscle sympathetic nerve activity (HyperPOTS) with 71% sensitivity and 85% specificity. In the treatment cohort, patients with HyperPOTS, identified by this clinical biomarker, more often reported clinical improvement (85% versus 44% in nonhyperadrenergic; =0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: -1.9±0.9 versus 0.1±0.5; =0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: -12.9±2.7 versus -2.2±2.2; =0.005) in response to guanfacine. These results are consistent with the concept that POTS is caused by a central sympathetic activation in a subset of patients, which can be identified clinically by an exaggerated DBP increase during phase 2 of the Valsalva maneuver and improved by central sympatholytic therapy. These results support further clinical trials to determine the safety and efficacy of guanfacine in patients with POTS enriched for the presence of this clinical biomarker.

Introduction SARS-CoV-2 infection (COVID-19) and the COVID-19 vaccine have been linked to the development of persistent symptoms, including orthostatic intolerance (OI) and postural orthostatic tachycardia syndrome (POTS), in both children and adults. POTS is characterized by excessive tachycardia and other symptoms upon standing, significantly impacting quality of life. This study aims to evaluate the clinical and laboratory findings in pediatric patients with post-COVID-19 or post-COVID-19 vaccine OI and POTS. Methods This retrospective chart review included pediatric patients under 18 years of age with chronic dizziness or syncope following COVID-19 infection or vaccination. Autonomic studies, including the tilt table test, Valsalva maneuver, deep breathing test, and Quantitative Sudomotor Axon Reflex Test (QSART), were conducted to assess autonomic function. Data on clinical symptoms, autonomic testing results, and sweat production were collected and analyzed. Results In total, 16 patients (mean age 15 ± 3 years) were included in the study, with 14 patients developing symptoms post-COVID-19 infection and two post-vaccination. Ten patients (62.5%) met the criteria for POTS, with an average delta heart rate of 49 bpm on tilt table testing. Seven patients (43.75%) showed abnormal results on the Valsalva maneuver, and 50% (four patients) of those who underwent QSART demonstrated small fiber neuropathy. The mean standing norepinephrine level was 520 picograms per milliliter (pg/mL), with some patients showing markedly elevated levels. Conclusion This study highlights the growing incidence of POTS and other forms of OI in pediatric patients following COVID-19 infection and vaccination, supporting the link between COVID-19 and autonomic dysfunction in children. Our findings contribute to the growing body of literature on Long-COVID and emphasize the need for greater awareness, as well as further research into its long-term autonomic effects.

Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily affects female patients. Despite the severity of POTS, there are no approved medications for use in patients with this disorder. Compression garments are a commonly prescribed nonpharmacological treatment, but little is known about the patient experience with compression. In this study we aimed to evaluate the patient experience with compression garments using a structured survey and semistructured telephone interviews. A focused survey was designed as a component of a larger clinical trial on compression garment use in patients diagnosed with POTS. Building on the survey, semistructured telephone interviews were conducted with POTS patients. Recorded interviews were transcribed and coded in a thematic analysis using a descriptive-interpretive approach. A total of 27 participants completed the survey, and 20 participants completed the telephone interview. Patient experiences with compression were variable, with some participants experiencing significant benefits, and others reporting minimal to no benefits. Six themes that influenced garment use were identified: the potential benefit of the garment to improve symptoms, specific activities patients will be undertaking, environmental conditions, garment attributes, psychological and cognitive aspects, and financial considerations. Participants engage in a daily cost-benefit analysis when making decisions to use a compression garment. Clinicians should be aware of the benefits of and factors that limit use of compression garments as a treatment for POTS.

Long-COVID is a new multisectoral healthcare challenge. This study aims at understanding experiences, knowledge, attitudes and (information) needs that GPs had and have in relation to Long-COVID and how these evolved since the beginning of the COVID-19 pandemic. The study used an exploratory qualitative research design using semistructured interviews. A total of 30 semistructured interviews with GPs in different primary care settings (single practices, group practices, primary care centres) were conducted between February and July 2022. The data were analysed using qualitative thematic content analysis with the software Atlas.ti. This is the first study that empirically investigated Long-COVID management by GPs in Austria during the third year of the pandemic. All GPs indicated having experience with Long-COVID. In cities, GPs tended to have slightly better networks with specialists. The GPs who already worked in teams tended to find the management of Long-COVID easier. The symptoms that the physicians described as Long-COVID symptoms corresponded to those described in the international literature, but it is unclear whether syndromes and symptomes such as Post-Exertional-Malaise, autonomic dysfunction such as postural tachycardia syndrome or Mast-Cell-Overactivation-Syndrom, and cognitive dysfunctions were also recognized and correctly classified since they were never mentioned. Most GPs reacted quickly by granting the needed sick leaves and by seeing and discussing with the patients often.The treatment of the patients is described as an enormous challenge and frustrating for patient and GP if the treatment does not yield to significantly improved health also due to the high costs for the patient. Long-COVID will continue to preoccupy our health care systems for a long time to come, as new variants of COVID-19 will continue to produce new patients without adequate prevention strategies. Therefore, it is not a question of if but when good support for GPs and adequate care pathways for people with Long-COVID will be implemented. Specific contact points that are familiar with therapy-refractory postacute infection syndromes like the postacute COVID condition as a subgroup of Long-COVID are urgently needed.

Exercise is a vital component of health and is commonly utilized as a non-pharmacologic therapy for many disorders, including postural orthostatic tachycardia syndrome (POTS). However, exercise intolerance is a key feature of POTS and other autonomic disorders and, therefore, presents a major barrier for many patients. Despite exercise being uniformly recommended as a therapeutic intervention, a majority of patients with POTS, especially those with severe orthostatic intolerance and fatigue, are unable to complete or sustain rigorous exercise programs or successfully integrate them into their daily routine. In this narrative review, we discuss the current literature on exercise and POTS and our clinical experience with a home-based exercise approach developed at the Dysautonomia Clinic. We conclude that individualized exercise programs that are delivered remotely by a certified physical therapist may be convenient, easily accessible, and safe for patients with POTS, especially those with severe symptoms who may be home- or bedbound. Future randomized controlled studies are needed to quantify and characterize the benefits of home-based exercise programs delivered remotely compared to standard therapy.

The global COVID-19 vaccination campaign, with 13.53 billion doses administered by early 2024, has significantly reduced severe illness and mortality. However, potential adverse effects, such as Postural Orthostatic Tachycardia Syndrome (POTS), have raised concerns. This systematic review evaluates the incidence, mechanisms, and clinical implications of POTS following COVID-19 vaccination. A systematic search of PubMed, EMBASE, and Web of Science was conducted up to June 7, 2024, following PRISMA guidelines to identify studies related to COVID-19 vaccines and POTS. Eligible studies included randomized controlled trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports. Screening, data extraction, and quality assessment were independently performed by two reviewers using the Joanna Briggs Institute Checklists and the Newcastle-Ottawa Scale. Of the 1,531 articles identified, 10 met the inclusion criteria, encompassing a total of 284,678 participants. These studies included five case reports, two case series, one cross-sectional study, one prospective observational study, and one cohort study. The cohort study reported that the odds of new POTS diagnoses post-vaccination were 1.33 (95% CI: 1.25-1.41) compared to the 90 days prior. In contrast, the post-infection odds were 2.11 (95% CI: 1.70-2.63), and the risk of POTS was 5.35 times higher (95% CI: 5.05-5.68) post-infection compared to post-vaccination. Diagnostic findings across studies included elevated norepinephrine levels and reduced heart rate variability. Reported management strategies involved ivabradine, intravenous therapies, and lifestyle modifications. The risk of POTS following COVID-19 vaccination is lower than that observed post-SARS-CoV-2 infection; however, existing studies are limited by small sample sizes and methodological variability. Further research is needed to clarify the incidence, mechanisms, and long-term outcomes of vaccine-related POTS to inform effective clinical management strategies.

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.

There are several mechanisms responsible for the dynamical link between heart period (HP) and respiration (R), usually referred to as cardiorespiratory coupling (CRC). Historically, diverse signal processing techniques have been employed to study CRC from the spontaneous fluctuations of HP and respiration (R). The proposed tools differ in terms of rationale and implementation, capturing diverse aspects of CRC. In this review, we classify the existing methods and stress differences with the aim of proposing a variability-based multi-method approach to CRC evaluation. Ten methodologies for CRC estimation, namely, power spectral decomposition, traditional and causal squared coherence,\;information transfer, cross-conditional entropy, mixed prediction, Shannon entropy of the latency between heartbeat and inspiratory/expiratory onset, conditional entropy of the phase dynamics, synchrogram-based analysis, pulse-respiration quotient, and joint symbolic dynamics, are considered. The ability of these techniques was exemplified over recordings acquired from patients suffering from postural orthostatic tachycardia syndrome (POTS) and healthy controls. Analyses were performed at rest in the supine position (REST) and during head-up tilt (HUT). Although most of the methods indicated that at REST, the CRC was lower in POTS patients and decreased more evidently during HUT in POTS, peculiar differences stressed the complementary value of the approaches. The multiple perspectives provided by the variability-based multi-method approach to CRC evaluation help the characterization of a pathological state and/or the quantification of the effect of a postural challenge. The present work stresses the need for the application of multiple methods to derive a more complete evaluation of the CRC in humans.

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic condition hallmarked by orthostatic intolerance and tachycardia in the upright position. POTS impacts approximately 1-3 million people in the U.S. alone, in which the majority of patients are premenopausal women. The etiology of POTS is multi-factorial with three primary clinical subtypes, including neuropathic, hyperadrenergic, and hypovolemic POTS. Recent evidence suggests potential metabolic associations with POTS pathophysiology, particularly involving insulin resistance and abnormal vasoactive gut hormones. This review aims to characterize POTS phenotypes and explore potential metabolic links, focusing on insulin resistance and vasoactive gut hormones. Understanding the metabolic aspects of POTS pathophysiology could provide novel insights into its mechanisms and guide therapeutic approaches.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder arising from mutations in the TGF- β signaling pathway. The spectrum of clinical manifestations is broad, and includes vascular, skeletal, and craniofacial abnormalities, along with joint hypermobility. No evidence of postural orthostatic tachycardia syndrome (POTS) in these patients has been reported. We report here a case series of patients with LDS presenting to the autonomic clinic and found to have POTS. Understanding the exact pathophysiology of this association requires further studies. Acknowledging the co-occurrence of these conditions is important to improve outcomes, and managing POTS in LDS patients necessitates an interdisciplinary approach.

Postural orthostatic tachycardia syndrome (POTS) is a frequently diagnosed cardiovascular disorder after COVID-19 infection. POTS is characterized by the presence of excessive sinus tachycardia on standing without a fall in blood pressure (BP). We investigated the BP profile using 24-hour ambulatory BP monitoring in patients with new-onset POTS after COVID-19 compared with prepandemic population-based controls. We performed a case-control study in 100 patients (mean age, 40.0±12.9 years; 85% women) with verified post-COVID-19 new-onset POTS diagnosed by a positive head-up tilt testing versus 100 controls from a population-based cohort with a negative active standing test, no history of syncope, POTS, or endocrine disease (mean age, 42.3±14.0 years; 78% women). Twenty-four-hour BP profile was assessed for circadian BP variation including hypotensive systolic BP (SBP) episodes (<80, <90, and <100 mm Hg). Patients with post-COVID-19 POTS had significantly higher nighttime SBP, but not daytime SBP, and more daytime SBP hypotensive episodes compared with controls. Nondipping (34% versus 19%; <0.001) and reverse dipping patterns (9% versus 0%; <0.001) were more frequent in post-COVID-19 POTS. In the logistic regression, patients with post-COVID-19 POTS had significantly higher mean 24-hour SBP (odds ratio, 1.08 [95% CI, 1.04-1.11]; <0.001) and nighttime SBP (odds ratio, 1.07 [95% CI, 1.04-1.10]; <0.001), independent of age and sex. Patients with post-COVID-19 POTS demonstrate higher mean 24-hour and nighttime SBP and show disruptions of circadian BP rhythm regulation compared with population-based controls, as well as more daytime hypotensive episodes. Future studies are needed to test whether patients with post-COVID-19 POTS may benefit from tailored BP therapy.

The National Childhood Vaccine Injury Act of 1986 created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. Since 1988, the total compensation paid exceeds $6 billion. Although postural orthostatic tachycardia syndrome (POTS) is a frequent reason for filing a claim, there has been no review of the process and validity of the legal outcomes given current medical information. The purpose of this study was to review vaccine-related POTS and assess the rationale behind decisions made by the court. We identified 102 unique cases with POTS. All published reports were reviewed for petitioner's theories supporting vaccine-induced POTS, respondent's counterarguments, the final decision regarding compensation, and the rationale underlying these decisions. The primary goal was to determine which factors went into decisions regarding whether vaccines cause POTS. In deciding the cases the Special Masters hearing the cases place a high reliance on expert witnesses for both the petitioners and respondents. Petitioners' experts frequently implicated vaccines, primarily human papillomavirus vaccine, as causing POTS through autoimmunity induced by molecular mimicry. However, in none of the 102 cases was POTS considered to be directly caused by a vaccine. Despite the lack of epidemiologic or mechanistic evidence indicating that childhood vaccines covered by the VICP result in POTS, these cases continue to be adjudicated, at considerable cost to the government. Unless there is emerging scientific support for implicating vaccines in POTS it is time that the VICP stop considering these cases.

Presently, numerous studies have demonstrated that long-term cardiovascular changes after Coronavirus Disease 2019(COVID-19) infection should be considered. The study was aimed to explore the risk factors for post COVID-19 long-term cardiovascular symptoms. This retrospective observational cross-sectional study involved 204 COVID-19 patients who were admitted to Yantaishan Hospital from January 1, 2023 to January 31, 2023. Demographic and laboratory data were collected and compared between patients who experienced post COVID-19 long-term cardiovascular symptoms and those who did not. Logistic regression analysis was used to identify the risk factors associated with the occurrence of post COVID-19 long-term cardiovascular symptoms. Fifty-two participants presented Post COVID-19 cardiovascular symptoms, while the remaining 152 individuals did not show any such symptoms including chest pain, chest tightness, shortness of breath, palpitations, dyspnea, exercise intolerance, and postural tachycardia syndrome. In comparison to the group without post COVID-19 long-term cardiovascular symptoms, the group with post COVID-19 long-term cardiovascular symptoms exhibited a significantly higher prevalence of anxiety and depression (25.0% vs. 4.6%,  = 0.000), as well as significantly elevated C-reactive protein (42.3 mg/L vs. 20.3 mg/L,  = 0.014) and D-dimer (0.3 mg/L vs. 0.22 mg/L,  = 0.024). Anxiety and depression (odds ratio [OR] = 6.403, 95% confidence interval [CI]:2.180-18.809,  = 0.001), C-reactive protein (OR = 1.009, 95%CI:1.003-1.015,  = 0.006), D-dimer (OR = 1.455, 95%CI:1.004-2.109,  = 0.048), and LDL-C (OR = 1.780, 95%CI:1.043-3.040,  = 0.035) were identified as independent risk factors for post COVID-19 long-term cardiovascular symptoms. Anxiety and depression, C-reactive protein, D-dimer, and LDL-C levels are associated with the development of post COVID-19 long-term cardiovascular symptoms.

Postural orthostatic tachycardia syndrome (POTS) represents chronic orthostatic intolerance. Patients usually suffer from presyncopal symptoms, such as lightheadedness, headache, blurred vision, and fatigue. Central hypovolemia, peripheral vascular dysfunction, and a hyperadrenergic state may contribute to the pathogenesis of POTS. It is necessary to comprehensively assess the clinical characteristics, physiological changes, and biochemical markers to select an appropriate therapy. Since the introduction of the concept of individualized treatment for POTS, great progress has been made in the field.

Orthostatic hypotension (OH) is a common cardiovascular disorder with high prevalence in the elderly. Concomitant venous return impairment may worsen the autonomic response and accentuate the symptoms. We detailed a patient with severe OH, prominent varicosities, and hemosiderin deposition in lower limbs. After excluding autonomic and neurological etiology, a computed tomography venography revealed significant common iliac vein compression. The patient was deemed to benefit from venous stenting. At a 2-year follow-up, the patient reported symptom improvement with adequate stent patency. Venous stenting may aid in the treatment of patients with severe OH symptoms without clear etiology and impairment of venous return.

: Patients with postural orthostatic tachycardia syndrome (POTS) or neurogenic orthostatic hypotension (nOH) experience vertigo, confusion, and syncope. Compression garments help reduce venous pooling in these patients, thereby increasing cardiac output. We aimed to determine end-user opinions of compression products intended to alleviate symptoms for POTS and nOH. : This was a survey study sampling participants diagnosed with POTS or nOH. The data collected included demographics, medical history, and compression garments previously used. The participants rated their most frequently used garment across comfort, aesthetic appeal, ease of use, durability, cost-effectiveness, efficacy, and consistency on the Likert scale (1-5). One-way ANOVA was used to compare the design criteria ratings across garments. For all tests α = 0.05. : Of the 330 POTS and 28 nOH participants surveyed (mean age 37.9, mean BMI 27.5, 95.0% women, 90.5% White), 354 (98.9%) reported trying at least one compression garment since their diagnosis. The majority of participants reported using leg compression most frequently rather than shapewear or abdominal compression (65.4% vs. 20.1% vs. 13.4%, respectively). Approximately 67.0% of participants tried multiple product types. Shapewear was reported to have greater concealability compared to abdominal or leg compression garments (mean 3.43 vs. 2.90 vs. 2.91, respectively; < 0.01). Shapewear and abdominal compression were rated to be less comfortable compared to leg compression (2.67 vs. 2.94 vs. 3.05, respectively; = 0.03). : The existing compression products do not fully meet needs of individuals with POTS or nOH, as evidenced by participant ratings on multiple domains. There is potential consumer demand for novel adjustable abdominal compression garments that are low-profile and comfortable when disengaged.

Median arcuate ligament syndrome (MALS) is a neurovascular disorder characterized by gastrointestinal symptoms due to celiac artery and ganglion compression. Limited literature primarily focuses on adults. This study aims to characterize clinical and histopathologic findings in pediatric MALS. Patients <18 years undergoing robotic MAL release, celiac ganglionectomy, and lymphadenectomy from 2020 to 2024 were evaluated. Clinical and histopathologic outcomes were analyzed. Twelve patients met inclusion criteria and were reviewed (15.7 ± 1.2 years, 75% female, BMI 20.9 [18.6-24.0] kg/m). Comorbidities included depression/anxiety (83%), postural orthostatic tachycardia syndrome (POTS) (50%), gastroesophageal reflux disease (GERD) (50%), nutrition support (50%), mast cell activation syndrome (MCAS) (42%), hypermobile Ehlers-Danlos syndrome (hEDS) (42%), other vascular compression syndromes (33%). All patients who received preoperative celiac plexus block had temporary symptom relief (10/10). Mean operative time was 119.7 ± 22.4 min. No intraoperative complications, 30-day readmissions, reoperations, or complications occurred. Histopathologically, 92% had fibroadipose tissue, 100% had reactive lymph nodes, none had intraparenchymal nerves, and one had lipogranulomas. Median fibrosis scores were 1 [0.5-2] on H&E and 2 [1-2] on trichrome. Fibrosis score severity was not significantly associated with symptom improvement (χ = 3.67, p = 0.16). Median postoperative celiac artery velocity was 258.5 [192.5-350.5] cm/s with a median change of -80.5 [-106.1-+82.8] cm/s from preoperative 308.0 [229.3-344.0] cm/s (S = -5.0, p = 0.55). Those with lower preoperative velocities were more likely to have symptom improvement postoperatively (S = 19, p = 0.04). MALS symptoms improved in 83%; however, despite reporting "MALS pain" was improved, 64% (all female) had other comorbidities such as POTS, MCAS, hEDS, and colonic dysmotility contributing to other ongoing symptoms. Robotic MALS surgery is safe and effective in pediatrics. Clinical improvement rates and fibrosis scoring are comparable to adults; however, findings reveal challenges with multiple comorbidities contributing to separate symptoms that may continue postoperatively, particularly in females. We recommend a multidisciplinary team approach in addressing comorbidities and optimizing medical and surgical care. IV.

: While the diagnosis of postural orthostatic tachycardia syndrome (POTS) is based on heart rate (HR) and blood pressure (BP) criteria, the pathophysiology of POTS is not fully understood as multiple pathophysiological mechanisms have been recognized. Also, cardiac function, being dependent on preload, afterload, contractility, and HR, has not been properly studied. Preload and contractility changes can be inferred from stroke volume index (SVI) changes during a tilt test. Afterload plays a minor role in POTS as a normal BP response is a prerequisite for POTS. Therefore, we analyzed the HR-SVI relation during a tilt test in myalgic encephalomyelitis (ME/CFS) patients with POTS and compared the data with ME/CFS patients with a normal HR-BP response and with that of healthy controls (HC). : In ME/CFS patients with either POTS ( = 233) or a normal HR-BP response ( = 507) and healthy controls ( = 48), we measured SVI (by suprasternal echo), HR, and BP during the tilt. : In all ME/CFS patients, the decrease in SVI was larger compared to HC. In patients with a normal HR-BP response and in POTS patients with a HR increase between 30-39 bpm, there was an inverse relationship between the HR increase and SVI decrease during the tilt, compatible with increased venous pooling. In POTS patients with a HR increase ≥40 bpm, this inverse relation was lost, and SVI changes were significantly less compared to POTS patients with a HR increase between 30-39 bpm, suggestive of a hyperadrenergic response. : In ME/CFS patients with POTS, two different hemodynamic profiles can be observed: in patients with a limited HR increase, mainly increased venous pooling is observed, while in patients with a large (≥ 40 bpm) HR increase the data are suggestive of a hyperadrenergic response. These two different profiles may have different therapeutic implications.

Internal tremor (IT) is often reported by patients with post-acute sequelae of SARS-CoV-2, also known as Long COVID, as a distressing and disabling symptom. Similarly, physicians are typically perplexed by the nature and etiology of IT and find it extremely challenging to manage. We describe a patient with Long COVID who experienced IT as part of post-COVID postural orthostatic tachycardia syndrome (POTS) and small fiber neuropathy (SFN) and review the limited literature available on this topic. Our patient's IT improved significantly after intravenous saline infusions, but there was no effect on IT with oral hydration, increased oral sodium chloride intake, neuropathic pain medications, muscle relaxants, or medications used for the treatment of POTS. Based on this case, our clinical experience, and the limited literature available to date, we believe IT is a manifestation of POTS and SFN, which may be driven by hypovolemia, cerebral hypoperfusion, sympathetic overactivity, neuropathic pain, and mast cell hyperactivation. Subjective description, objective findings, and diagnostic and therapeutic considerations in patients with IT and Long COVID are discussed.

To evaluate the relationship between Renin-Angiotensin-Aldosterone System (RAAS) activity and Perfusion Index (PI) in children with Postural Tachycardia Syndrome (POTS), and to assess the diagnostic performance of Angiotensin II (AngII) and PI for POTS status. A total of 65 children with POTS and 65 age- and sex-matched healthy controls were enrolled. Plasma renin, angiotensin I (AngI), AngII, and aldosterone were quantified via enzyme-linked immunosorbent assay, and PI was measured using a pulse oximetry-based monitor during head-up tilt testing. Statistical analyses included Receiver Operating Characteristic (ROC) curve analysis of AngII and PI for POTS status, binary logistic regression, and Pearson correlation. Compared to controls, children with POTS demonstrated a significantly lower PI (4.64 ± 1.54 vs 6.19 ± 1.64%; adjusted < 0.005) and higher AngII levels (114.07 ± 7.69 vs 109.20 ± 10.44 pg/mL; adjusted = 0.012). ROC analysis indicated that PI had a stronger diagnostic value (AUC = 0.753, 95% CI: 0.670-0.836) than AngII (AUC = 0.654, 95% CI: 0.559-0.749) in identifying POTS. In logistic regression, only PI remained an innt predictor of POTS (Odds Ratio = 0.577, 95% CI: 0.442-0.755, < 0.001). A significant inverse correlation was observed between AngII and PI (r = -0.459, < 0.001). PI is a valuable, noninvasive clinical marker for POTS in children, demonstrating superior diagnostic utility compared to AngII. While elevated AngII retains clinical significance by reflecting underlying pathophysiology and disease severity, its independent predictive value is limited. The combined assessment of PI and AngII may enhance the pathophysiological understanding and management strategies for pediatric POTS.

Autonomic disorders, especially those characterized by orthostatic intolerance such as Postural Tachycardia Syndrome (POTS), remain diagnostically and therapeutically challenging due to their complex pathophysiology and limited access to specialized care. This paper proposes a conceptual framework for applying digital twin technology to POTS and other autonomic disorders. A digital autonomic twin-a dynamic, virtual replica of a patient's autonomic system-offers a transformative approach to understanding, predicting, and managing these conditions. A dynamic digital twin framework integrates mechanistic and AI-based modeling utilizing continuous physiological, clinical, genetic, and patient-reported data to enhance individualized diagnosis, disease monitoring, and treatment. This system can simulate autonomic responses, predict disease trajectories, and personalize interventions. Digital twins provide real-time physiological modeling, adaptive treatment simulations, lifestyle intervention tracking, and integration of environmental and biometric data. Key components include wearable devices, electronic health records, AI-driven simulations, and clinician interfaces. However, challenges such as data volume, model transparency, and ethical considerations must be addressed. In conclusion, digital twin technology has the potential to revolutionize the management of POTS and related autonomic disorders, transitioning to personalized, predictive, adaptive medicine by providing a continuously updated and tailored approach to neurological care.

Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope, and orthostatic hypotension are the most common autonomic disorders encountered in clinical practice. The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. However, the treatment of common autonomic disorders has traditionally included pharmacologic and non-pharmacologic symptomatic therapies as the standard approach. Unfortunately, these symptomatic therapies have been of limited or insufficient efficacy to meaningfully improve functional status or result in recovery, especially in patients with severe symptoms. Case reports, case series, and clinical experience suggest that intravenous and subcutaneous immunoglobulin, as well as other immunologic therapies (such as plasmapheresis, corticosteroids, and rituximab), may be effective in some patients with severe POTS and other common autonomic disorders who are refractory to standard therapies. In this narrative review, we summarize the literature available on the topic of immunotherapies for POTS, other common autonomic disorders, and Long COVID. We also highlight the need for large, multicenter, placebo-controlled trials of immunoglobulin, plasmapheresis, intermittent corticosteroids, and other repurposed immunotherapies in patients with common autonomic disorders who have significant functional impairment.

Postural tachycardia syndrome (POTS) is a common autonomic dysfunction in children. The head-up test (HUT) or head-up tilt test (HUTT) is typically required to confirm the diagnosis of POTS. This study describes a novel approach to diagnosing POTS in children by simultaneous measurement and analysis of heart sounds and electrocardiogram (ECG) signals using a wearable device. To evaluate the diagnostic value of synchronous heart sound and ECG monitoring in identifying POTS in children. This study included a total of 50 children. Twenty-five children with POTS were admitted to the hospital with symptoms of syncope or orthostatic intolerance, while twenty-five children who came to the hospital for a health checkup were included as the control group. All children underwent synchronous phonocardiography and ECG monitoring with wearable devices to simultaneously record heart sounds and ECG signals. Wavelet analysis was used to automatically analyze heart sounds and ECG signals to determine the Electromechanical Activity Time (EMAT). In the POTS group, EMAT decreased significantly from supine to upright position (75.71 ± 9.16 ms vs 70.90 ± 10.86 ms, P = 0.0051), while the change in the control group was not significant (58.92 ± 4.10 ms vs 55.50 ± 9.89 ms, P = 0.100). The difference in EMAT change (upright-supine) was significantly greater in the POTS group (3.39±5.91 ms) than in controls (0.58 ±5.70 ms, P = 0.038).Precision-recall curve (PRC) analysis demonstrated that the average precision (AP) for EMAT in the supine position was 0.84, while the AP for the upright position was 0.88. Simultaneous heart sound and ECG analysis using a wearable device is a simple, noninvasive approach that aids in the diagnosis of pediatric POTS. EMAT serves as a valuable discriminative marker between patient groups.