Postural orthostatic tachycardia syndrome (POTS) is a complex disorder with challenging diagnosis and management. This cross-sectional, multi-national, web-based physician chart audit described clinical features and management of POTS, offering insights into disease burden and outcomes before and after the COVID-19 pandemic. Physicians (n = 153), primarily cardiologists (77.1 %), reported data from 599 patients from two cohorts: 1) POTS not triggered by COVID-19 (n = 361) and 2) POTS triggered by COVID-19 (n = 238). Overall, most patients experienced POTS symptoms onset between the ages of 18 and 39 years (33 %), with 13 % presenting symptom onset before 18 years of age. Over 70 % had at least one pre-existing medical condition. Most patients underwent 5-8 tests to define POTS diagnosis. Around 80 % received incorrect diagnoses before POTS confirmation, and 25 % waited over a year for diagnosis. Although some patients showed reduction in symptom severity over time, symptoms were still persistent at last consultation. Non-pharmacological interventions were common in the first treatment line. In subsequent lines, there was an increase in pharmacological treatments, with beta-blockers and ivabradine being the most frequently prescribed medications. Comparative analysis between pre- and post-COVID-19 POTS showed that while POTS patients triggered by COVID-19 were somewhat older and had fewer comorbidities, differences were not clinically meaningful, suggesting similar diagnostic, management and treatment patterns. Regional differences in diagnoses and treatment patterns were observed between US and Europe. This study highlights the challenges faced by POTS patients, while providing insights into the diagnostic and treatment approaches in real-world settings.

Postural Orthostatic Tachycardia Syndrome (POTS) is a debilitating condition of the autonomic nervous system with no clear referral, diagnosis, and treatment pathways. Patients experience high levels of symptoms and moderate levels of distress. The purpose of this study was to explore biopsychosocial factors associated with distress in those under investigation for POTS, to identify potential targets for intervention. A longitudinal, quantitative survey. Participants (n = 149) completed demographic, psychosocial, and symptom questionnaires prior to a diagnostic POTS clinic visit and 6 months follow-up (n = 98). Correlation and regression analyses were used to identify factors associated with distress at baseline (within one month before diagnostic hospital visit) and at 6 months follow up. At baseline, distress levels were moderate and greater symptom focusing, all-or-nothing and avoidance behaviours, threatening views of the illness, emotional reactivity, cardiac anxiety, POTS symptoms, number of specialists seen, lower social support, and younger age were significantly associated with higher levels of baseline distress. The baseline regression model including all demographic, clinical, and psychosocial factors explained 61.2 % of the variance in distress, with the psychosocial variables collectively explaining 55.6 % of this variance (F = 11.06, p < .001). There was no significant difference between distress levels at baseline and follow-up. Psychosocial variables explained 4.7 % of the variance (F = 0.76, p = .665) in changes in distress scores over 6 months. Baseline distress scores accounted for the vast majority of variance in distress at follow-up. This study identified key novel psychosocial factors that were significantly associated with distress which could be potential targets for intervention. Additional factors such as younger age and a higher number of specialists seen were also associated with higher levels of distress, which merits attention when assessing patients' psychological wellbeing this patient group. Distress levels did not significantly change following the specialist consultation and investigation.

BackgroundIndividuals with neurologic impairment, such as brain injury, are more likely to have autonomic dysfunction, including POTS, but often experience a lack of treatment options and access to quality care.ObjectiveExamine the feasibility and outcomes of a group-based multimodal rehabilitation training program.MethodsNineteen females, ages 18-53 (M = 28.6) completed the outpatient training program. The intervention included eight 50-min weekly sessions using an interdisciplinary, multimodal approach, including education, movement, and mindful self-compassion. Participants completed demographic and medical history and assessment for baseline orthostatic intolerance. At pre-training, post-training, and follow-up, participants completed the Modified Fatigue Impact Scale (MFIS), Lower Extremity Functional Scale (LEFS), Rand 36-Item Health Survey 1.0 (RAND-36), Trail Making Test (A and B) (TMT-A, TMT-B), 10-Meter Walk Test (10MWT), and grip strength testing.ResultsAt baseline, participants were significantly below norms in daily function (p < 0.001), grip strength (p ≤ 0.001) gait speed (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Between pre-training and follow-up, participants showed significant improvement across function in daily life tasks (p < 0.01); grip strength in the dominant (p < 0.01) and non-dominant (p < 0.01) hands; gait speed (p < 0.05); levels of fatigue (p < 0.05); cognitive performance (p < 0.05); and quality of life (p < 0.05).ConclusionIndividuals with POTS face functional challenges that can be significantly and objectively improved through multimodal rehabilitation. There is a need for provider education and further research to optimize care and quality of life for individuals with POTS.

Twenty five percent of children who sustain a mild traumatic brain injury (mTBI) or concussion experience persisting post-concussion symptoms (PPCS). The symptoms of PPCS significantly overlap with postural orthostatic tachycardia syndrome (POTS). We aimed to review the literature and investigate the prevalence of POTS in children and adolescents recovering from mTBI. This single centre controlled cross-sectional cohort study recruited children (aged 8-18 years inclusive) diagnosed with mTBI in the emergency department. At 4-6 weeks postinjury, children completed the Active Stand Test. The primary outcome was change in heart rate alongside clinical symptoms consistent with POTS. A total of 113 participants (64 PPCS, 24 mTBI with no clinical symptoms [asymptomatic], and 25 healthy controls) of similar age (mean 13.9 years) and sex (n = 55 [48.7%] male) underwent orthostatic testing. There were no significant group differences in heart rate or blood pressure at baseline, or within 10 minutes of standing. Three (4.8%) symptomatic participants satisfied POTS diagnostic criteria, compared to zero asymptomatic and one (4.2%) control participant. Using the Active Stand Test, a small proportion of children with PPCS satisfied clinical POTS criteria. Although it should be considered in the differential diagnosis, POTS is not common nor overrepresented in PPCS.

Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing. The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review. Evidence on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.

Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among this patient population. The purpose of this mixed-methods study was to provide greater understanding of the perceived barriers, preferences, perceptions of exercise, and experiences implementing exercise recommendations for adults with POTS in order to optimize treatment recommendations and intervention design. This study consisted of a series of focus groups (n = 29) and an online survey of adults with POTS (n = 255) focusing on exercise engagement, beliefs, barriers, and facilitators. Qualitative data were analyzed using an iterative inductive-deductive approach, informed by social cognitive theory, which resulted in a conceptual framework and a series of themes. Survey results showed that participants reported a wide range of exercise frequency prior to the onset of POTS symptoms, and overall lower exercise engagement post-POTS. In both survey results and qualitative findings, participants reported believing that exercise is important in managing POTS, but identified barriers to exercise training, including most saliently, their symptom burden. Participants also identified important needs and facilitating factors that could support them in engaging in regular exercise to help manage their condition. These findings shed light on the patient experience of exercise in POTS, which can inform both the tailoring of exercise recommendations and the design of interventions to support exercise engagement specific to the POTS population.

The association between blood pressure variability (BPV) or heart rate variability (HRV) and the baroreflex is well established. However, the role of the vestibular-autonomic reflex in regulating BP and HR stability has primarily been explored only in experimental studies. We aimed to delineate the association of BPV and HRV with otolith function in postural orthostatic tachycardia syndrome (POTS). We retrospectively analyzed data from consecutive patients with POTS recruited between April 2021 and April 2025 at a tertiary referral-based hospital in South Korea. All patients underwent a head-up tilt table test using a Finometer device and cervical (cVEMP) and ocular vestibular evoked-myogenic potentials (oVEMP). The Finometer data were analyzed using a power spectral analysis. The Finometer, cVEMP, and oVEMP data were compared with those of 32 age- and sex-matched healthy participants. A total of 47 patients with POTS (mean age standard deviation [SD] = 33 10 years; 30 female patients) and 32 age- and sex-matched healthy participants were included for analysis. The n1-p1 amplitude of oVEMP was larger in patients with POTS than in healthy participants (p = 0.002). p13 latency was negatively correlated with the SD of heart rate in the supine position in patients with POTS (p = 0.001), a trend not observed in healthy participants. The n1-p1 amplitude (odds ratio [95% confidence interval] = 1.27 [1.08-1.49], p = 0.004) and root mean square of successive differences (RMSSD) during tilting (0.82 [0.72-0.93], p = 0.001) were associated with POTS after adjusting for other covariates. Otolithic function may play a role in accentuating BPV and HRV in POTS by contributing to enhanced sympathetic outflow.

Patients with Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Intolerance (OI) commonly present with symptoms suggestive of Pelvic Venous Disorders (PeVD). The presence of PeVD may contribute to orthostatic symptoms in these patients due to venous obstruction with stasis and pooling. Iliac vein compression, a PeVD, has historically been treated with iliac venous stenting. The authors hypothesize that patients with POTS frequently have findings of PeVD, that venous outflow obstruction from iliac vein compression exacerbates POTS/OI symptomatology, and that treating PeVD improves POTS/OI symptoms. This paper reports results from two studies at two different institutions with a partially overlapping patient population. The first was a retrospective cross-sectional observational study of patients with POTS/OI who presented to Emory University Cardiology (Atlanta, GA, USA) from October 2019 to June 2023. We aimed to evaluate the prevalence of concurrent POTS/OI and PeVD using screening pelvic venous ultrasound, MR and/or CT, compared to venogram with intravascular ultrasound (IVUS). We secondarily evaluated the efficacy of each imaging modality in screening accuracy for PeVD. The second study was a retrospective review of medical records for 271 female patients with POTS/OI who received treatment of PeVD with iliac vein stenting from June 2019 to November 2024 at Minimally Invasive Procedure Specialists (Highlands Ranch, CO). The primary objective of this study was to explore quality of life (QoL) outcomes in female patients with POTS/OI before and after treatment. The secondary objective was to record the prevalence of associated pelvic pain, systemic symptoms, and response to therapy in this population. In the first cohort, 129 patients (84% cis female) with a diagnosis of POTS/OI and symptoms of PeVD were assessed by standard imaging for venous pathology. 107 patients (83%) had confirmed pelvic venous compression (iliac vein, renal vein, or both) or pelvic venous congestion on imaging with at least one screening modality. All screening modalities were relatively insensitive in detecting iliac venous compression compared with venography and IVUS. In the second cohort, following iliac vein stenting, significant improvements were seen in Orthostatic Hypotension Questionnaire (OHQ) composite scores at three months (p < 0·001) and at 12 months (p < 0·001). The OHQ Symptom Assessment (OHSA) and Daily Activities Scale (OHDAS) subscores, International Pelvic Pain Society (IPPS) score, Pelvic Congestion Syndrome (PCS) score, Pelvic Pain and Urgency/Frequency Symptom Scale (PUF) score, and Ancillary symptom score all demonstrated statistically significant decreases at three months that persisted at 12 months (all p < 0·001) as well. The high prevalence of PeVD in POTS/OI patients suggests an association between the two diagnoses. In the absence of expert clinical review, screening with US, CT, and MR may not be sufficient to rule out PeVD. Significant improvements were seen in QoL in patients with POTS/OI and PeVD who underwent iliac vein stenting. These results call for additional trials to examine the clinical and hemodynamic effects of venous stenting on POTS/OI symptomatology and associated systemic symptoms, including pelvic pain. These studies received no funding.

The objective of this study was to investigate the potential association between the use of calcitonin gene-related peptide (CGRP) antagonists and the reporting of cardiac adverse events (cAEs) by analyzing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). CGRP antagonists are a novel class of effective treatments for migraine. However, given CGRP's crucial role as a potent vasodilator, concerns about the cardiac safety of its long-term blockade persist. This study aimed to assess real-world post-marketing safety signals for this drug class. FAERS data from Q1 2018 to Q2 2025 were analyzed. CGRP antagonists included monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and small-molecule receptor antagonists (rimegepant, ubrogepant, atogepant). Disproportionality analyses were conducted using the reporting odds ratio (ROR) and information component (IC). The impact of age, sex, and weight on cAE was assessed. Time-to-onset analyses were also carried out. A total of 1806 cAE reports associated with CGRP antagonists were identified. Palpitations emerged as a consistent signal across all seven agents, suggesting a class effect. Monoclonal antibodies, particularly erenumab and fremanezumab, exhibited a broader spectrum of cAE signals, including coronary artery dissection, Prinzmetal angina, and postural orthostatic tachycardia syndrome. The results showed higher body weight was significantly associated with the cAE signal of disproportionate reporting (SDR) of erenumab (odds ratio [OR] 1.48, 95% CI 1.02-2.11, P = 0.034). Meanwhile, male sex was significantly associated with the cAE SDR of galcanezumab (OR 2.41, 95% CI 1.25-4.40, P = 0.006). Time-to-onset analyses indicated that most cAEs followed an early failure pattern, with the highest reporting intensity shortly after treatment initiation. Using FAERS, this pharmacovigilance study detected signals of disproportionate reporting of cardiac adverse events for most CGRP antagonists. These results are hypothesis-generating and reflect reporting patterns rather than incidence or relative risk; therefore, they should not be interpreted as evidence of causality or as patient-level cAE risk factors. Continued post-marketing surveillance and confirmatory pharmacoepidemiologic studies in well-defined populations are warranted.  CLINICAL TRIAL NUMBER: Not applicable.

Tachycardia upon standing implicates cardiovascular dysreflexia, potentially resulting from impaired autonomic regulation. However, the pathophysiology of POTS remains unclear. Here, we evaluated the central nervous system in postural orthostatic syndrome (POTS). The purpose of this study was to evaluate brain tissue changes, functional networks (the central autonomic network), and cerebral hemodynamic status in patients with POTS using magnetic resonance imaging (MRI) and autonomic reflex challenges. Individuals with POTS and age- and sex-matched healthy controls were enrolled. Brain MRI data were collected with a 3.0-T scanner at rest and during functional MRI using 3 autonomic reflex challenges: passive leg raise, mental arithmetic, and isometric handgrip reflex. 38 participants were enrolled (18 patients with POTS and 20 controls). No significant differences emerged in age, sex, or body mass index between patients with POTS and controls (P > .05). Patients with POTS had higher anxiety and depression symptoms. Although global screening indicators of cognitive function were preserved (Montreal Cognitive Assessment test: POTS vs controls, 28 ± 1 vs 29 ± 1; P = .2), executive function was slowed in POTS (Trail Making Test Part B: POTS vs controls, 44 ± 12 vs 67 ± 34; P = .008). Brain tissue structural changes (P < .005) and reduced cerebral blood flow appeared in patients with POTS compared with controls (P < .005). Furthermore, impaired neural responses were seen in patients with POTS during passive leg raise, mental arithmetic, and isometric handgrip reflex challenges (P < .005), despite preserved peripheral reflex function (P > .05). Patients with POTS show evidence of brain tissue structural changes, impaired central neural responses, and reduced cerebral blood flow in autonomic regulatory sites during cardiovascular reflex testing. These findings indicate that central autonomic control deficits may help explain cardiovascular dysreflexia in POTS.

How is postural orthostatic tachycardia syndrome (POTS) diagnosed? What about adolescents who seem to have POTS but do not meet the diagnostic criteria? How can we treat POTS and related conditions? How can we best respond to common questions of frustrated patients and parents and guardians? This article provides evidence- and expert-based answers to questions that frequently arise when caring for patients with POTS and related conditions.

Autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), is increasingly recognized in adolescents and young adults. Early recognition in primary care is critical, as these conditions can substantially affect functioning, school participation, quality of life, and health care utilization. This review provides practical, clinically relevant guidance for pediatric and family medicine clinicians, and emphasizes recognition, office-based assessment, initial management, and referral strategies. Key considerations include differentiating POTS from mimicking conditions, evaluating functional impact, and implementing structured lifestyle interventions. Medications are reserved for patients with significant functional impairment despite conservative management, with a focus on setting realistic expectations. Case vignettes illustrate common phenotypes and highlight practical approaches to individualized care. By providing clear frameworks for evaluation and management, primary care clinicians can reduce unnecessary specialty visits, improve patient outcomes, and facilitate coordinated care across multidisciplinary teams.

Ehlers Danlos and related hypermobility syndromes underly chronic, recurrent, and multiple-site pain in a small number of persons. By making the diagnosis, clinicians can better guide the treatment of the presenting problem. The diagnosis can help a patient make sense of their recurrent challenges as well. By inquiring about numerous associated conditions, ranging from postural orthostatic tachycardia syndrome to autism spectrum and attention deficit issues, the clinician may help the patient deal with other challenges. Detection can be easy-primarily observation of flexibility in the thumb, finger, elbow, and knee. The diagnosis is missed commonly, so we recommend clinicians take 1 month to perform these maneuvers on all chronic pain patients as one way of ensuring that clinicians have awareness.

Postural orthostatic tachycardia syndrome (POTS) is characterized by orthostatic tachycardia with associated symptoms including presyncope, fatigue, dizziness, and gastrointestinal complaints, among others. In addition to cardiovascular and neurologic features, autonomic dysfunction may involve other organ systems. We report a rare case of transient evanescent hyperemia occurring during presyncopal episodes in a patient with POTS, highlighting a potentially underrecognized dermatologic sign of autonomic dysfunction. We present a 19-year-old female with known POTS and a complex medical history including pituitary adenoma (prolactinoma), secondary adrenal insufficiency, gastroparesis, severe malnutrition, and pelvic floor dysfunction, who was admitted for recurrent presyncope, syncope, and collapse. Her presentation was multifactorial. Contributing factors included autonomic instability, cabergoline-related effects, and nutritional compromise. During hospitalization, she developed recurrent episodes of transient, sharply demarcated erythematous patches affecting the face, chest, and upper extremities that coincided with presyncope and resolved spontaneously without intervention. Dermatology evaluation supported a diagnosis of evanescent hyperemia in the setting of autonomic dysfunction associated with POTS. Diagnostic workup included serial laboratory testing, electrocardiography, echocardiography, neuroimaging, and multidisciplinary specialty consultations. Transthoracic echocardiography demonstrated a patent foramen ovale with preserved cardiac function, without evidence of structural heart disease contributing to her symptoms. Management required a multidisciplinary approach, including stress-dose intravenous hydrocortisone for adrenal insufficiency, adjustment of cabergoline due to suspected medication-related bradycardia, continuation of fludrocortisone for volume support, and initiation of nasoduodenal tube feeding for nutritional rehabilitation. This case illustrates a transient cutaneous finding temporally associated with presyncope in a patient with POTS and complex comorbidities. Awareness of such skin changes during symptomatic episodes may provide supportive clinical clues to underlying autonomic dysfunction, particularly in diagnostically challenging presentations.

More than five years after the start of the COVID-19 pandemic, its long-term effects are increasingly coming into focus. Post-COVID disease poses a significant challenge, - not only for the individuals affected, but also for healthcare providers and society as a whole. In order to improve care for post-COVID patients, the current state of research should be reviewed and the frequent and characteristic complaints post-exertional malaise and postural tachycardia syndrome should be presented. The literature search for this narrative review was conducted in the PubMed and Semantic Scholar databases. Post-COVID symptoms are often nonspecific, diverse, and fluctuating. However, post-exertional malaise and postural tachycardia syndrome are characteristic of post-COVID when they occur newly after COVID-19 disease. Post-exertional malaise is an intensification of symptoms after exertion that occurs in about 86% of post-COVID patients. Pacing is a promising treatment approach here. Postural tachycardia syndrome manifests as autonomic, tachycardic, orthostatic dysregulation and affects up to 82% of post-COVID patients. Symptomatic therapy includes pharmacological and non-pharmacological measures. Post-exertional malaise and postural tachycardia syndrome are typical and characteristic post-COVID symptoms. Current scientific findings underscore the SARS-CoV-2-related organic origin of post-COVID symptoms.

Patients with postural orthostatic tachycardia syndrome (POTS) frequently report higher rates of chronic gastrointestinal symptoms, disorders of gut-brain interaction (DGBI), and extra-intestinal co-morbidities. We conducted a systematic review and meta-analysis to assess the prevalence of gastrointestinal symptoms and comorbid conditions in POTS patients. Electronic databases were searched from inception until May 2025 for studies reporting gastrointestinal symptoms in POTS patients. A random-effects model was used to pool the proportion of POTS patients reporting gastrointestinal symptoms, and sub-group analyses were conducted. The final dataset includes 19 studies, with 8268 POTS patients, revealing that 57.9% (95% CI 38.4-75.2) had at least one gastrointestinal symptom. The most common gastrointestinal symptom was nausea (70.1%, 95% CI 51.5-83.7) followed by bloating (64.9%, 95% CI 48.5-78.4), abdominal pain (60.4%, 95% CI 39.2-78.3) and postprandial fullness (60.4%, 95% CI 45.6-73.6). Irritable bowel syndrome was the most prevalent DGBI, affecting 26.8% (95% CI 15.3-42.4) of POTS patients. The most common extraintestinal comorbidity was anxiety, reported in 42.9% (95% CI 22.7-65.8), followed by chronic fatigue (40.9%, 95% CI 21.1-64.2), migraine (35.6%, 95% CI 27.0-45.2), depression (34.4%, 95% CI 19.0-54.0), and fibromyalgia (21.6%, 95% CI 12.8-34.2). Approximately one third reported mast cell activation syndrome (36.3%, 95% CI 17.8-60.0) and joint hypermobility syndrome (31%, 95% CI 24.4-38.5). There was substantial heterogeneity seen in the primary and most subgroup analyses. Overall, 60% of POTS patients report concurrent gastrointestinal symptoms, with nausea being the most common. IBS affects 25% of patients with POTS. Notably, extra-intestinal comorbidities-primarily anxiety, chronic fatigue, migraines, depression, and fibromyalgia-are more prevalent than gastrointestinal conditions in this population.

Cardiac autonomic dysfunction is a well-established sequela of concussions, most commonly manifesting in the postconcussive period. Athletes are typically susceptible to these forms of injury. This article summarizes the scope of existing research on this topic, providing evidence and clinical experience of the evaluation, diagnostic modalities, differential diagnoses, and treatment considerations from the sports cardiology perspective.

Temperature intolerance is a common and often debilitating symptom of postural tachycardia syndrome (POTS), however treatment options are limited. In this open-label pilot study, we examined the use of a novel wearable thermal watch (Embr Wave2™) on thermoregulatory and other autonomic symptoms in POTS. Participants with POTS and temperature intolerance were recruited from the Stanford autonomic disorders clinic. All patients completed an online battery of autonomic and sleep questionnaires including the composite autonomic symptom score-31 (COMPASS-31), the Delphi interoceptive scale, the temperature disturbance index scale (TDIS), and a 10-minute active stand testing at baseline and after 4 weeks of wearable use. Twenty-two POTS participants with severe temperature intolerance were included in the final analysis. At baseline, 55% noted a moderate to severe impact of temperature intolerance on quality of life (QoL). After 4 weeks of wearable use, sustained reductions were seen across multiple TDIS domains, including work, leisure activities, and enjoyment of life (p ≤0.05). No significant changes were seen in COMPASS-31 scores (53.98 [43.36-56.62] vs. 53.04 [44.66-60.30], p = 0.34) or orthostatic tachycardia on stand testing (31.5 [24.8-45.5] bpm vs.31.0 [21.0-40.5] bpm, p = 0.56). Temperature intolerance is common and directly correlated with QoL in patients with POTS. Use of a non-invasive thermal wearable led to improvement in temperature related QoL measures, however global autonomic symptom scores and orthostatic tachycardia remained unchanged. This study highlights the need for other treatment studies with more specific patient reported outcomes measures in POTS patients with temperature intolerance.

Muscle sympathetic nerve activity (MSNA) is valuable for managing postural tachycardia syndrome (POTS), but microneurography is clinically impractical. We investigated whether the Valsalva phase 2 diastolic blood pressure rise (DBP) serves as a sympathetic marker and proposed enhanced neurovascular transduction as a pathophysiological mechanism in hyperadrenergic POTS. We included 21 POTS women and 22 healthy women to perform Valsalva and microneurography. MSNA spike rate was obtained using stationary wavelet transformation. The DBP cut point for hyperadrenergic POTS was optimized by the golden section search with its correlation to phase 2 MSNA spike rate as an objective function. We defined peripheral sympathetic neurovascular transduction (psNVT) as a ratio of DBP to early phase 2 MSNA increase. We compared Valsalva responses between the identified hyperadrenergic and non-hyperadrenergic POTS. The DBP strongly correlated with the Valsalva phase 2 MSNA spike rate percentage change from baseline in healthy (r = 0.874, p < 0.001). The DBP cutoff criterion of 15 mmHg optimally separated POTS into 7 hyperadrenergic (≥ 15 mmHg, r = 0.902, p = 0.014) and 14 non-hyperadrenergic (< 15 mmHg, r = 0.629, p = 0.021). Although similar MSNA spike rate, the hyperadrenergic group had higher baseline systolic blood pressure (118 ± 10 vs 105 ± 12 mmHg, p = 0.026), shorter pressure recovery time (1.15 ± 0.75 vs 2.59 ± 1.17 s, p = 0.048), and higher psNVT (2.60 ± 1.02 vs 0.58 ± 0.46 mmHg/spike·s, p < 0.001) than the non-hyperadrenergic POTS. DBP ≥ 15 mmHg could be a sympathetic clinical marker and could identify hyperadrenergic POTS, characterized by enhanced neurovascular transduction despite comparable MSNA levels. This novel pathophysiological insight underscores the importance of sympathetic markers in POTS clinical management.

Our overarching objective was to determine whether autonomic reflex dysfunction and heightened sensory sensitivity contribute to orthostatic intolerance (OI) in patients with migraine. Adults with migraine (N = 30) underwent autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal/adrenergic baroreflex sensitivity (BRS-V/A). Postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension/hypertension were diagnosed during tilt table testing. A cold pressor test (CPT) evaluated sympathetic vasomotor function. Participants completed the Migraine Disability Assessment (MIDAS), the 2011 Fibromyalgia (FM) Survey Criteria, and chronic overlapping pain condition (COPC) screening. The number of headache days per month correlated with CASS (p = 0.001), BRS-V (p < 0.001), and the CPT (p = 0.003) in the expected direction, with increasing autonomic nervous system (ANS) reflex dysfunction correlating with increasing number of headache days. During tilt testing, OI was prevalent (25/30; 83%) and was reported by all patients with chronic migraine. An abnormal cardiovascular response to tilt was present in 63%; POTS was the most common etiology (56.2%). Patients reporting OI during tilt table testing despite a normal cardiovascular response (33%) had higher FM scores (15.8 ± 3.6 vs. 7.5 ± 4.6; p < 0.01) and a greater prevalence of non-headache COPCs (88.8% vs. 20.0%, p = 0.02) than asymptomatic patients. Increased headache frequency correlates with increasing ANS reflex dysfunction. The high prevalence of OI in patients with migraine may be due to both autonomic reflex dysfunction and an abnormal cardiovascular response to tilt (i.e., concordant OI) and heightened sensory sensitivity (i.e., discordant OI).

Patients with postural orthostatic tachycardia syndrome (POTS) experience disabling symptoms such as brain fog related to reduced cerebral perfusion. The objective of this study is to determine the mediating role of carbon dioxide in the relationship between stroke volume and cerebral blood flow. A total of 15 female patients with POTS underwent head-up tilt testing under two conditions: with lower-body compression (higher stroke volume) and without (lower stroke volume). We analyzed cerebral blood flow velocity, respiratory, and cardiovascular responses using linear mixed-effects and mediation models to examine stroke volume-cerebral blood flow interactions. Granger causality and wavelet coherence assessed cerebral autoregulation. Lower-body compression attenuated the reduction in stroke volume (-34 ml versus -23 ml; p < 0.01), end-tidal CO (-6.4 mmHg versus -3.2 mmHg; p < 0.01), and mean middle cerebral artery blood flow velocity (-11.2 cm/s versus -4.2 cm/s; p < 0.01) during tilt. Mediation analysis revealed that carbon dioxide completely mediated the relationship between stroke volume and middle cerebral artery blood flow velocity, with a significant indirect effect (0.18 cm/s/ml, 95% confidence interval (CI) 0.058-0.33) and a nonsignificant direct effect (0.04 cm/s/ml, p = 0.5). Compression attenuated the association between stroke volume and carbon dioxide (-0.07 mmHg/ml; 95% CI -0.12 to -0.010; p = 0.02), as shown by the linear mixed-effect model, and reduced the directional influence of blood pressure on cerebral blood flow (ΔGranger causality: 0.12 (0.05-0.18) versus 0.05 (0.02-0.08); p < 0.01). Reduction in stroke volume leads to reduced cerebral perfusion in POTS, an effect likely mediated by decreased carbon dioxide.

In pediatric postural tachycardia syndrome (POTS), presyncope is important yet undercharacterized. It undermines school participation and daily function, while objective bedside markers remain limited. We aimed to delineate clinically usable predictors by integrating cardiovascular responses and cerebral oxygenation during active standing. We operationalized presyncope as visual darkening and examined three physiological correlates: heart rate change (ΔHR), recovery time, and cerebral oxygenation (ΔOxyHb). We conducted a cross-sectional study of 49 pediatric patients with POTS (median age 14.2 years, 46.9% male). Continuous heart rate, blood pressure, and cerebral oxygenation were recorded during a 10-min active standing test; body mass index, inferior vena cava collapsibility index, and urinary sodium were also obtained. Robust regression identified independent predictors of visual darkening. ΔHR emerged as the strongest predictor of visual darkening (coefficient 0.017, 95% CI 0.005-0.030, p = 0.004), followed by recovery time (coefficient 0.005, 95% CI 0.000-0.010, p = 0.055) and ΔOxyHb (coefficient 0.029, 95% CI  - 0.005 to 0.064, p = 0.098). The final model demonstrated strong discriminative ability (AUC 0.842). Patients reporting visual darkening exhibited significantly higher ΔHR (49 [42-59] vs. 41 [38-46] bpm, p = 0.009), longer recovery time (21 [19-28] vs. 19 [17-22] s, p = 0.041), and greater ΔOxyHb reduction (- 8.7 [ - 10.4 to - 2.4] vs. - 3.5 [- 7.0 to - 2.5] μmol/L, p = 0.039). Heart rate change upon standing is the most significant and clinically accessible predictor of visual darkening in pediatric POTS. The combined assessment of ΔHR, recovery time, and cerebral oxygenation offers a comprehensive evaluation of the risk of visual darkening, enabling personalized management strategies for pediatric patients.

Postural orthostatic tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS) are frequently observed causes of orthostatic intolerance (OI). Clinical experience reveals patients with overlapping symptoms of both. This observation led to the hypothesis of orthostatic tachycardia hypotensive syndrome (OTHS), a distinct OI variant, combines POTS and NCS features. This study aims to define and characterize it. A retrospective chart review of patients presenting with OI and underwent head up tilt (HUT) between 2014 and 2020. We extracted demographic data, findings during HUT including heart rate (HR), systolic blood pressure (SBP), stroke volume (SV), near infrared spectroscopy (NIRS), syncope, cardiac asystole, and convulsions. We divided the subjects into three groups: POTS, NCS, and OTHS. We included patients with POTS (n = 90), NCS (n = 86), and OTHS (n = 101). POTS patients showed higher HR (baseline, recovery, minimum) vs. OTHS (p = 0.047, < 0.001, < 0.001), while OTHS patients had higher HR (5 min, 10 min, minimum, maximum) vs. NCS (p = 0.047, < 0.001, < 0.001, < 0.001). Minimum SBP was higher in POTS vs. OTHS (p < 0.001), and OTHS patients had higher SV (baseline, recovery, minimum, maximum) vs. POTS (p = 0.006, < 0.001, 0.002, 0.005). Patients with POTS have lower baseline NIRS compared to NCS and OTHS (p =  < 0.032, < 0.011). Asystole was significantly more frequent in the NCS group (n = 24, 27.9%) than in the OTHS group (n = 9, 8.9%), with p < 0.001. OTHS is a form of OI characterized by initial orthostatic tachycardia with increased HR > 30-40 bpm followed by hypotension leading to syncope.

This study evaluated the cerebrospinal fluid (CSF) proteomes from 31 patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We quantified 902 proteins, each expressed in at least eleven samples, and systematically categorized clinical factors relevant to ME/CFS symptoms-including autonomic dysfunction, neuroinflammation and metabolic disturbances. Differentially expressed protein and pathway analyses evaluated protein features associated with both postural orthostatic tachycardia syndrome (POTS) status and disease severity among the patients, while ratio-based analysis further explored associations with severity ratings. Data are available via ProteomeXchange with identifier PXD076216. Neutrophil degranulation and platelet activation were enriched in patients with POTS, and several pathways, such as the complement cascade, coagulation-related pathways and IGFBP‑mediated insulin-like growth factor transport, were enriched in severe cases. Ratio-based analysis identified four biologically interpretable severity-associated protein ratios related to cellular stress, extracellular remodelling and immune-neuronal interaction. Together, these findings provide insight into the biological processes associated with clinical heterogeneity in ME/CFS and generate hypotheses for future validation in larger independent cohorts.