Postural orthostatic tachycardia syndrome (POTS) is a complex and heterogeneous autonomic disorder with limited effective treatment options. Noninvasive neuromodulation, particularly transcutaneous vagus nerve stimulation (tVNS), has recently emerged as a promising adjunctive therapy; however, substantial knowledge gaps remain. This article reviews the current evidence and highlights key limitations in the application of tVNS for POTS, including the lack of robust randomized controlled trials, small sample sizes, and inconsistent stimulation protocols across studies. The heterogeneity of POTS subtypes and the absence of validated biomarkers further complicate the interpretation of therapeutic outcomes. In addition, real-world applicability, long-term safety, and the mechanistic pathways underlying tVNS effects in POTS are insufficiently understood. Emerging areas such as the use of neuroimaging, physiological biomarkers, and cognitive assessments offer opportunities to deepen mechanistic insight and refine patient selection. Future studies should prioritize patient phenotyping, protocol standardization, and comprehensive outcome measures to improve clinical translation. Integrating tVNS into multimodal treatment strategies could enhance individualized care for POTS, but rigorous, high-quality research is needed to establish its long-term efficacy and safety. Addressing these challenges will be critical for determining the therapeutic role of tVNS in this disabling condition.

: Orthostatic intolerance is prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), CBF is regulated complexly, and cardiac output (CO) is an important determinant of CBF. A review in HC showed that a 30% reduction in CO results in a 10% reduction in CBF. In contrast, we showed in ME/CFS patients with a normal HR (HR) and blood pressure response during a tilt test that CO and CBF decreased to a similar extent. The relation between CO and CBF in ME/CFS patients with postural orthostatic tachycardia syndrome (POTS) is unknown. Therefore, the aim of this study is to assess the relation between CBF and CO, in ME/CFS patients with POTS. The methods used in this retrospective study analyze this relation in a large group of patients. We also analyzed the influence of clinical data. A total of 260 ME/CFS patients with POTS underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO. We measured CBF using extracranial Doppler flow velocity and vessel diameters obtained with a General Electric echo system, and suprasternal aortic flow velocities were measured using the same device. We recorded end-tidal PCO using a Nonin Lifesense device. : End-tilt HR and the HR increase were significantly higher in the patients with a %CO reduction ≥ -15% than in the other group. End-tilt CO was higher and the %CO reduction was lower in patients with %CO reduction ≥ -15% than in the other group. CBF data (supine, end-tilt and the %CBF reduction) were not different between the two patient groups. The use of HR increases and %SV reductions were not as discriminative as the %CO reduction. : In ME/CFS patients with POTS during tilt testing with measurements of both the CO and the CBF, two different patterns were observed: (1) appr. two-thirds of patients had an almost 1:1 relation between the %CBF reduction and the %CO reduction. (2) Appr. one-third of patients showed a limited reduction in CO together with a substantial increase in HR. In these patients, there was no relation between the CO and CBF reduction. These data suggest the presence of a hyperadrenergic response.

Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines have been associated with numerous side effects since their widespread release to the public. Cardiovascular complications include myocarditis and pericarditis, Takotsubo cardiomyopathy, postural orthostatic tachycardia syndrome (POTS), arrhythmias, sudden cardiac death, and cardiac tamponade. Pulmonary complications are pulmonary embolism (PE), interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), pneumonia, eosinophilic granulomatosis with polyangiitis, pneumonitis, and pulmonary hypertension. Despite these complications, the risk-benefit analysis still strongly favors vaccination, as these events occur more frequently with natural infection and confer a significantly worse prognosis. This study outlines the evidence surrounding each attributed effect, the clinical course including diagnosis and management, and the proposed pathophysiology. To our knowledge, this is the most comprehensive review of the cardiopulmonary effects of COVID-19 vaccination to date.

The prevalence and phenotype of capillaroscopic abnormalities in patients with autonomic nervous system dysfunction have not yet been investigated. Multiorgan involvement in dysautonomia entails abnormal vasoreactivity. We aim to correlate the diagnosis of autonomic dysfunction with certain clinical manifestations, which may provide prognostic or diagnostic information using a noninvasive technique, i.e., nailfold video capillaroscopy (NVC). Patients with autonomic nervous system dysfunction were recruited from rheumatology and neurology clinics with voluntary NVC procedures from 31 January 2024 to 10 January 2024, and a comparison with normal controls was performed. Additional recorded information include demographics and diagnoses of autonomic dysfunction types by autonomic testing, including, but not limited to, the following: reflex screen, sweat test, Valsalva maneuver, nerve fiber density, electromyography (EMG), serology, and history of autoimmune diseases. NVC was performed on a total of 27 patients. This study was approved by the Mayo Clinic Institutional Review Board. The autonomic dysfunction group consisted of small-fiber neuropathy (37%), orthostatic hypotension (48%), autonomic neuropathy (30%), limited autonomic neuropathy (7%), postural orthostatic tachycardia syndrome (POTS) (7%), and connective tissue disease (7%), among other types. Patients with autonomic dysfunction had statistically significant increases in microhemorrhages, dilated capillaries, and ramifications when compared to controls. Autonomic dysfunction was associated with statistically significant microvascular abnormalities compared to normal controls with a distinct NVC pattern. There was a statistically significant correlation between age and BMI with microvascular abnormalities. Here, we demonstrate the diagnostic potential of NVC in autonomic dysfunction and advocate for further study of capillary structures in autonomic dysfunction.

Objective: The aim of this study was to assess active standing test responses in ovewrweight or obese children and to determine the factors that contribute to orthostatic abnormalities. Materials and Methods: Orthostatic responses were investigated in bothobese and overweight children. To provide an overview of the autonomic nervous system (ANS), blood pressure and heart rate measurements, laboratory parameters, and anthropometric measures were analyzed. Results: A total of 123 overweight or obese children, with a median age of 15.03 (range from 6.9 to 17.9), were included in this study. Seventy-seven patients (63%) were obese, whereas 46 (37%) were overweight. Orthostatic disturbances were observed in 78 patients (63%). In the standing test, 73 patients (59%) exhibited an abnormal response. Orthostatic hypotension (33%), ortho- static hypertension (30%), and postural orthostatic tachycardia syndrome (18%), were detected in the patients. The group that had orthostatic hypotension had a lower systolic pressure in the standing test after 10 min. The group with orthostatic hypertension had higher body mass index. Furthermore, the orthostatic group displayed significantly higher levels of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulin, and HbA1c. Conclusion: The results of this study signifies a connection between obesity or being overweight and ANS, . highlighting the need for evaluation of the ANS in obese or overweight children to predict the adverse consequences and to prevent occuring during childhood.

The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.

Coronavirus disease 2019 (COVID-19) is a significant risk factor for autonomic dysfunction, with approximately 20% of COVID-19-infected children suffering from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). The autonomic nervous system regulates functions like blood pressure and heart rate, and the disruption of the system can lead to issues such as postural orthostatic tachycardia syndrome (POTS) and orthostatic dysregulation (OD). Individuals with autonomic dysfunction may have a heightened risk of sudden death during diving activities. We report the case of a patient who drowned after diving in a bathtub following COVID-19 infection. The patient exhibited findings consistent with POTS during the head-up tilt test (HUTT), suggesting the influence of autonomic dysregulation. A healthy 9-year-old boy had a mild COVID-19 infection. He recovered but experienced difficulty getting out of bed. Nevertheless, his daily activities remained largely unaffected. On the 11th day post-infection, he lost consciousness while diving in a bathtub and was quickly rescued by his father. Initial assessments revealed mild aspiration pneumonia and OD. On day 20, a HUTT revealed tachycardia, confirming POTS. Bathing alone was prohibited, and a reevaluation three months later indicated subjective symptom improvement, with no evidence of POTS during HUTT. This case highlights the potential association between mild autonomic dysfunction post-COVID-19 and increased drowning risk during cardiovascular-intensive activities like diving. Even when subjective symptoms are minimal, using tests such as HUTT to assess potential underlying autonomic dysfunction can help prevent secondary accidents.

The real-world use of head-upright tilt-table tests (HUTTs) in North America is not known. This single-centre retrospective study in Toronto, Ontario, Canada reports on 1063 HUTTs conducted between 2014 and 2024. Use of the HUTT increased year over year, with a greater increase in HUTTs conducted as a result of a referral diagnosis of postural orthostatic tachycardia syndrome (POTS). Using specific diagnostic criteria for syncope and POTS, patients with either diagnosis who underwent testing, after January 2021 had an almost 50% reduction in the odds of a positive HUTT (syncope: odds ratio: 0.54, 95% confidence interval: 0.40-0.73 and postural orthostatic tachycardia syndrome: odds ratio: 0.51, 95% confidence interval: 0.28-0.95).

To better understand why some postural orthostatic tachycardia syndrome (POTS) patients incorporate exercise regularly into their treatment and what barriers challenge others. POTS is a chronic autonomic condition in which patients experience orthostatic intolerance and abnormal tachycardia. Exercise is often recommended as a self-care modification, but many POTS patients face barriers to optimizing exercise. We sent an institutional review board-approved survey via the patient e-messenger (MyChart, Epic Systems, Verona, WI) to 421 patients who participated in a shared medical appointment (SMA) by Zoom (Zoom Video Communications, San Jose, CA) within our tertiary care center between March 2022 and October 2022. The survey gathered data for the following variables: demographics, gender, body identity, symptoms that interfere with exercise, exercise tolerance, exercise prescription, attitude toward exercise, and exercise resource accessibility. Of the 421 patients messaged through MyChart, 260-286 (61.75%-67.93%) responses were formally submitted per question. A total of 221/283 (78.09%) patients have had exercise recommended as a lifestyle modification; 220/286 (76.92%) patients exercised regularly before experiencing POTS symptoms; 167/271 (61.62%) patients were unsatisfied with their exercise regimen; 111/271 (40.95%) felt like others are critical of how much they exercise; 157/267 (58.80%) patients did not feel proud of how their body looks; 116/265 (43.77%) said they are ashamed of their body; 137/265 (51.69%) patients said exercise makes them feel worse; 176/266 (66.16%) patients wanted to stop exercising due to excessive sweating; 220/267 (82.39%) patients experienced dizziness while exercising; 159/266 (59.77%) patients experienced nausea while exercising. Most patients include exercise in their POTS treatment plan, and have a background in exercise before being diagnosed. However, many patients have negative self-identity and body image post diagnosis and experience symptoms while exercising that create barriers to physical activity. Managing exercise barriers for POTS patients in care delivery could improve exercise outcomes.

Patients with autonomic dysfunction, or dysautonomia, often report discolouration of their dependent extremities, which is thought to be from venous pooling or acrocyanosis. A subset of patients with SSc are affected by dysautonomia but may be challenging to identify. We sought to determine whether patients with SSc who report discolouration in their feet have a higher burden of autonomic symptoms, including orthostatic, gastrointestinal (GI), urinary, secretomotor and pupillomotor. 167 patients with SSc completed the Composite Autonomic Symptom Score (COMPASS)-31 survey, which queries whether the patient experiences discolouration of the feet or hands. We compared the COMPASS-31 subdomain scores between SSc patients with and without foot discolouration. Seventy-nine patients with postural orthostatic tachycardia syndrome (POTS) also completed the COMPASS-31 questionnaire for comparison. We found that extremity discolouration is common in POTS and more often affects the feet, whereas in SSc, the hands are more frequently involved; 62% of SSc patients report colour changes in their feet. These patients are more likely to have other autonomic symptoms, including orthostatic (11.7 ± 10.6 vs 8.6 ± 9.9, P = 0.06), GI (11.3 ± 4.3 vs 8.8 ± 4.3, P = 0.0003), urinary (1.4 ± 1.5 vs 0.8 ± 1.3, P = 0.002) and secretomotor (7.0 ± 3.8 vs 5.9 ± 3.8, P = 0.06) symptoms. These associations persist in a multivariable model after adjusting for potential confounders. Dependent extremity discolouration is common in dysautonomia. Patients with SSc who report colour changes in their feet are more likely to report other symptoms of autonomic dysfunction.

The aim of the current study was to test the effectiveness of treatment with bright light therapy (BLT) on fatigue and cognitive function in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A randomized-controlled cross-over study design was chosen in order to provide all patients access to BLT treatment and account for placebo effects. In this study, a total of 36 outpatients with a diagnosis of ME/CFS according to the criteria of the Institute of Medicine (2015) were randomly assigned to a cross-over design starting out either with BLT or waitlist for the course of 2 weeks with a washout phase in between. Portable light boxes emitting full-spectrum visible light with a luminance intensity of 10,000 lux were used by the participants at home. Primary outcome of the study was fatigue as assessed by Chalder Fatigue Score (CFQ) and the secondary outcome variable was cognitive function assessed per standardized test battery (Test of Attentional Performance - TAP). The primary outcome variable fatigue was not significantly improved after treatment with BLT compared to wait list in the full crossover design, although fatigue scores improved immediately after two weeks of BLT. Additionally, patients showed decreased reaction time after treatment with BLT in a subtest of TAP compared to wait list. Over 45 % of patients were diagnosed with postural tachycardia syndrome. BLT for two weeks is not effective for the treatment of fatigue in ME/CFS, but it might have beneficial effects on attention in patients with ME/CFS. The clinical trial is registered with www. gov (NCT06635928).

Orthostatic intolerance (OI) is defined as the development of characteristic symptoms while standing, which significantly improve by recumbency. The most common forms are vasovagal syncope (VVS), orthostatic hypotension, and postural orthostatic tachycardia syndrome (POTS). Lately, there has been a growing body of evidence that autoimmunity may play a role in the pathophysiology of orthostatic intolerance syndromes. The aim was to compare the presence and levels of autoimmune autoantibodies in patients with POTS, VVS syncope, and the control group. Altogether, 61 patients with symptoms of orthostatic intolerance were evaluated in this study - 19 POTS patients and 42 VVS patients. The control group contained 22 patients with no signs of orthostatic intolerance. We evaluated levels of autoantibodies against three subtypes of G-protein coupled adrenergic receptor (alpha-1 and beta-1,2 adrenergic receptors), type 4 of muscarinic acetylcholine receptor, and angiotensin II type 1 receptor. We compared the levels between the three patient groups. Significantly higher levels of angiotensin II type 1 receptor (AT1R) autoantibodies were found in the POTS group compared with controls (0.67± 0.35 ng/ml vs. 0.38±0.32 ng/ml, p=0.008). There was no significant difference in AT1R antibodies between the VVS and control groups (0.46±0.34 ng/ml vs 0.38±0.32 ng/ml, p= 0.38). Autoantibody concentration against ADRA1, ADRB1, ADRB2, and M4R were not significantly different between the groups. Autoimmune mechanisms may lead to abnormal regulation of the renin-angiotensin-aldosterone system and may contribute to the pathophysiology of POTS.

Although the acute phase of the COVID-19 pandemic has subsided, the emergence of the post-COVID-19 condition presents a new and complex public health challenge, characterized by persistent, multisystem symptoms that can endure for weeks or months after the initial infection with the SARS-CoV-2 virus, significantly affecting survivors' quality of life. Among the most concerning sequelae are cardiovascular complications, which encompass a broad spectrum of conditions, including arrhythmias, myocardial damage, or postural orthostatic tachycardia syndrome. This narrative review explores the burden of the SARS-CoV-2 infection on cardiovascular health by reviewing the latest and most relevant findings in the literature and highlighting different aspects of COVID-19's cardiovascular involvement. This review investigates the pathophysiological mechanisms underlying cardiovascular involvement in the post-COVID-19 condition, with a focus on direct viral invasion via ACE2 receptors, immune-mediated cardiovascular injury, cytokine storm, systemic inflammation, endothelial dysfunction, and mitochondrial injury. The interplay between pre-existing cardiovascular diseases, such as hypertension, atherosclerosis, diabetes, and atrial fibrillation, and COVID-19 is also explored, revealing that individuals with such conditions are at heightened risk for both severe acute illness and long-term complications. Long-term immune activation and the persistence of viral antigens are increasingly recognized as contributors to ongoing cardiovascular damage, even in individuals with mild or asymptomatic initial infections. As the healthcare system continues to adapt to the long-term consequences of the SARS-CoV-2 pandemic, a deeper understanding of these cardiovascular manifestations is essential. This knowledge will inform the development of targeted strategies for prevention, clinical management, and rehabilitation of affected patients. Furthermore, the insights gained from the intersection of COVID-19 and cardiovascular health will be instrumental in shaping responses to future viral epidemics, highlighting the necessity for multidisciplinary approaches to patient care and public health preparedness.

To explore the impact of school periods and long holiday periods on the occurrence of neurally mediated syncope (NMS) in children. A retrospective analysis was conducted on 262 children with NMS. The children were aged 4-17 years, 119 males. 244 cases were diagnosed as vasovagal syncope, and 18 cases as postural orthostatic tachycardia syndrome. The data on the age, sex, syncope triggers, hemodynamic types, family history of syncope of children with syncope during long holiday periods group (n = 68) and school periods group (n = 194) were compared. (1) Incidence of syncope: The incidence of syncope during school periods (74.05%) was higher than that during long holiday periods (25.95%). (2) Comparison of sex and triggers: The constituent ratio of females with syncope during school periods was higher than that of males (P < 0.05). Among the triggers, the proportion of sudden postural change during long holiday periods was higher than that during school periods (26.47% vs. 21.13%, P < 0.05). (3) Univariate analysis: Situational syncope was a potential protective factor when syncope occurred during school periods (OR 0.23, 95%CI 0.07-0.76, P < 0.05), and being female was a potential risk factor (OR 1.92, 95%CI 1.10-3.35, P < 0.05). (4) Comparison of multiple models: In the risk of syncope occurring during school periods, situational syncope reduced the risk by 79% compared with no trigger, and being female increased the risk by 78% compared with being male. The occurrence of NMS-related syncope events in children is associated with school periods and long holiday periods. During school periods, being female is a risk factor for syncope, while situational syncope is a protective factor.

Managing postural tachycardia syndrome (POTS) requires continuous symptom monitoring, yet effective tools for patient self-management are limited. This study assessed patient perspectives on a wearable app designed for POTS management. Participants valued features like real-time heart rate monitoring and symptom tracking, which reduced cognitive strain and fostered confidence. Challenges such as navigation and alert management highlighted the need for improved interface design and customization. These findings demonstrate the app's potential to enhance self-management and foster patient autonomy. Future research should examine long-term outcomes and integrate suggested improvements to optimize patient-centered POTS care.

The current study aims to investigate the factors associated with the severity of conditions for pediatric cases with postural orthostatic tachycardia syndrome (POTS). Patients hospitalized and first diagnosed with POTS were retrospectively included and reviewed. The severity of symptoms was evaluated by symptom scores (SSs). Multiple Spearman correlation analyses and multiple linear regression analyses were used to determine factors independently associated with SS. Patients were divided into the mild (SS ≤ P25) and severe (SS ≥ P75) groups to test the distinguishing efficiency of the candidate factors. The efficiency of each independently correlated factor in indicating the condition of children with POTS was assessed by the receiver operating characteristic (ROC) curve. A series of 296 pediatric patients aged 5-17 years suffering from POTS were included. Multiple Spearman correlation analyses and multiple linear regression analyses showed that corrected QT interval dispersion (QTcd) was independently correlated with SS ( < 0.05). QTcd can be used to suggest the severity of POTS symptoms, and the area under the curve (AUC) was 0.986 (95% CI 0.976-0.997). At a threshold of QTcd = 45 ms, the sensitivity and specificity were, respectively, 94.0% and 91.8% for symptom severity indication. In pediatric cases with POTS, QTcd was positively correlated with their symptom severity and exhibited a strong indicative value. A QTcd of 45 ms was a valid cut-off value for indicating symptom severity.

Syncope is a common cause of the transient loss of consciousness, with neurally mediated syncope (NMS) and particularly vasovagal syncope (VVS) being the most prevalent types among older children and adolescents. VVS is primarily caused by heightened parasympathetic activity triggered by emotional or postural stimuli, resulting in a temporary disruption of circulation. Although anamnesis and physical examination play key roles in diagnosing VVS, additional diagnostic methods are necessary in unclear cases. This study aims to evaluate the long-term outcomes of pediatric patients with syncope, focusing on clinical characteristics, diagnosis, and treatment approaches. A retrospective analysis was conducted on 455 pediatric patients aged 8-21 years who presented with syncope at our cardiology clinic between 2005 and 2023. Patients diagnosed with cardiac syncope, epilepsy, or postural orthostatic tachycardia syndrome (POTS) were excluded. The remaining 283 patients were categorized into two groups: those with confirmed VVS-based on a comprehensive evaluation, including medical history, physical examination, and electrocardiography-and those suspected of VVS who lack a confident diagnosis after an initial assessment requiring tilt table testing. Clinical features, diagnostic methods, and treatment outcomes were analyzed. The study cohort had a mean age of 13.5 ± 1.6 years, with a female predominance of 69%. Among patients who underwent tilt table testing (TTT), 74.8% exhibited a positive response, with mixed-type syncope being the most prevalent (51%). Syncope recurrence was significantly higher in the TTT group (54%) compared to the clinically diagnosed group (15%) ( < 0.001). Relapse risk was strongly associated with the syncope subtype, particularly cardioinhibitory type 2B (OR: 2.3, 95% CI: 1.1-4, < 0.01), and episode frequency (OR: 1.7, 95% CI: 1.3-2.5, = 0.03). Beta-blocker therapy was selectively administered and demonstrated a reduced relapse risk in a univariate analysis. VVS is a significant health issue in pediatric patients and the therapeutic modalities available encompass various interventions, including modifications to lifestyle, adequate hydration, and pharmacological therapies. TTT was found to be an effective diagnostic tool for identifying high-risk patients and is recommended for appropriate cases in pediatric VVS diagnosis in accordance with the guidelines, with the objective of refining therapeutic methodologies and ultimately augmenting patient prognoses.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating condition characterized by autonomic dysregulation. Patients with this disorder may experience orthostatic intolerance, palpitations, fatigue, and a wide variety of other symptoms. The neuropathic symptoms of POTS may be caused by small fiber neuropathy (SFN), which is currently diagnosed using skin nerve biopsy. Corneal confocal microscopy (CCM) is an imaging modality that allows visualization of the corneal nerve layer. Our study aimed to determine whether CCM could detect differences in small nerve fiber parameters between POTS patients with and without signs or symptoms of SFN. CCM was performed on nine patients, along with a neurological examination. Participants were also asked about neuropathic symptoms by a researcher. Based on examination findings and/or reported symptoms, patients were categorized into SFN+ and SFN- groups for comparison. A chart review was conducted to gather demographic data, medications, autonomic testing results, and medical history, including common POTS comorbidities. Comparison of nerve fiber parameters using CCM did not reveal a statistically significant difference between the groups. However, valuable insights were gained regarding the logistics of conducting this type of study in POTS patients, including adapting to challenges and improving coordination between the neurology and ophthalmology departments. CCM may one day replace skin nerve biopsy as a diagnostic tool for SFN in POTS patients. Although this preliminary analysis did not demonstrate significant findings, likely due to the small sample size, we believe CCM may still have a role in POTS research and could eventually become a diagnostic tool used in autonomic clinics.

The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients' symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients' psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan's (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person's experiences with illness. We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia. Consistent with Linehan's theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay. Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

To assess the effects of two different body positions on the cardiovascular autonomic profile during a single bout of exercise in patients with postural orthostatic tachycardia syndrome (POTS). Thirteen patients with POTS and thirteen healthy controls (C) participated in the study. ECG, respiration, beat-by-beat arterial pressure and O consumption (VO2) were continuously recorded while on a cycle ergometer in supine and upright positions, before and during exercise (6 min, 50 Watts). Spectral analysis of RR intervals and systolic arterial pressure (SAP) variability provided indexes of cardiac sympathovagal interaction (LF/HF ratio), cardiac vagal modulation (HF, high-frequency component of RR variability, ~ 0.25 Hz), sympathetic vasomotor control (LF, low-frequency component of SAP variability, 0.1 Hz) and baroreflex sensitivity (BRS, α). While supine, patients with POTS showed lower HF and α, greater heart rate (HR), LF/HF and LF, compared with C, suggesting cardiovascular sympathetic over-activity and reduced BRS. While sitting upright, POTS showed greater HR and reduced HF and α compared with C. During supine exercise, SAP, HR, LF/HF increased and HF and α decreased similarly in POTS and C. In POTS, upright sitting exercise was associated with slightly higher , a greater increase in HR whereas LF was lower than in C. Upright exercise was associated with excessive enhancement of HR and a blunted increase of the sympathetic vasomotor control in POTS. Conversely, supine exercise-induced hemodynamic and autonomic changes similar in POTS and C, thus making supine exercise potentially more suitable for physical rehabilitation in POTS.

We compared standing and upright tilt in patients with postural tachycardia syndrome (POTS) and healthy volunteers to determine whether standing accurately tests for POTS in youngsters < 19 years. POTS in adolescents is defined by orthostatic intolerance plus sustained excessive upright tachycardia, without hypotension during upright tilt. We examined whether active standing is a valid classifier for POTS in adolescents compared to tilt. Patients with POTS (N = 36, 12.2-18.8 years) and healthy volunteers (N = 39, 13.1-18.9 years) performed stand for a minimum of 5-min and were tilted to 70° for 10 min. Receiver operating characteristics analyses (ROC) were performed at 5-min stand, and at 5  and 10 min tilt for optimal threshold for heart rate (HR) increase (ΔHR), and test sensitivity and specificity. Most subjects were unable to stand for 10 min. ΔHRs at 5 min stand were higher in POTS (31 ± 3) compared with control (21 ± 2) and elevated at 5- or 10-min tilt in POTS (51 ± 3 and 51 ± 2) versus control (26 ± 2 and 25 ± 2) compared with standing. ΔHR in POTS and controls for 10 min were not different from 5 min. For 5 min stand ROC threshold was 26 beats per min (bpm), sensitivity of 70.6%, and specificity of 68.2% compared with 39 bpm, 88.2%, and 95.1% for 5 min tilt, and 40 bpm, 94.1%, and 95.1% for 10-min tilt. A precision-recall graph confirmed the superior discriminating ability of 5 min and 10 min tilt compared to 5 min stand. The stand test is relatively non-specific and imprecise compared to tilt and does not satisfactorily distinguish POTS from control in patients aged < 19 years old.

The semiautomated carbon monoxide (CO) rebreathing method has been introduced as a noninvasive and radiation-free blood volume estimation method. We tested whether the semiautomated CO rebreathing method can detect the blood volume deficit in postural orthostatic tachycardia syndrome (POTS). In addition, we explored the relationship between blood volume estimated from CO rebreathing and body impedance. We recruited 53 subjects (21 female patients with POTS, 19 healthy female participants, and 13 healthy male participants) to record blood volumes and hemodynamic data. Blood volumes were measured by CO rebreathing and segmental body impedance. Linear regression models to predict normal values of red blood cell volume (RBCV), plasma volume (PV), and total blood volume (BV) were developed. Percentage deviations from the predicted normal volumes were calculated. Patients with POTS had lower RBCV (25.18 ± 3.95 versus 28.57 ± 3.68 mL/kg, p = 0.008, patients with POTS versus healthy female participants), BV (64.53 ± 10.02 versus 76.78 ± 10.00 mL/kg, p < 0.001), and BV deviation (-13.92 ± 10.38% versus -0.02 ± 10.18%, p < 0.001). Patients with POTS had higher supine heart rate (HR) (84 ± 14 versus 69 ± 11 bpm, p < 0.001) and upright HR (123 ± 23 versus 89 ± 22 bpm, p < 0.001). We found a correlation between BV deviation and upright HR in patients with POTS (r = -0.608, p = 0.003), but not in healthy participants. Volumes from the CO rebreathing and body impedance were well correlated (r = 0.629, p < 0.001). The CO rebreathing method can detect BV deficit, as well as the RBCV deficit in patients with POTS. The negative correlation between BV deviation and upright HR indicates that hypovolemia is one of the pathophysiological causes of POTS. Correlations between body impedance and CO rebreathing volume suggest its usefulness for measurements of volume changes.

The aim of the study is to analyze and compare the cognitive profile between 59 patients with long-COVID [LC; 30 of them with and 29 without a positive coronavirus disease 2019 (COVID-19) confirmatory test] and 31 patients with postural orthostatic tachycardia syndrome (POTS) and a matched group of 39 healthy control participants. Participants were examined on a battery of neuropsychological tests, including verbal memory, visuospatial abilities, attention, processing speed, verbal fluency, working memory, and visual memory. Anxious-depressive symptomatology was also analyzed and then controlled for possible influence on cognitive performance. Patients with LC and POTS showed significantly lower performance compared with healthy peers. Differences on anxious and depressive symptoms were also found between the clinical and control groups, resulting in LC without a positive confirmatory test group exhibiting the highest rates of anxious symptoms. After controlling the effects of anxious-depressive symptomatology, the differences were eliminated for some of the cognitive variables, but additional differences were found between patients with LC and POTS after post hoc analysis. Findings from the present study contribute toward the reinforcement of the evidence on cognitive alterations associated with LC and POTS. Anxious-depressive symptomatology has to be considered in both clinical groups since it could be affecting cognitive performance.

Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We compared autonomic function between patients with long-COVID and healthy controls, and within patients with long-COVID with different orthostatic hemodynamic phenotypes. Patients with long-COVID (n = 94; F = 76; 42 years [36, 53 years] with initial orthostatic hypotension: n = 40; F = 32; 49 years [39, 57 years]; postural orthostatic tachycardia syndrome: n = 29; F = 26; 39 years [33, 47 years]; or no abnormalities: n = 25; F = 18; 42 years [35, 49 years]), and healthy controls (n = 33; F = 25; 49 years [30, 62 years]) completed a 10-min active stand with beat-to-beat hemodynamics. Heart rate variability, blood pressure variability, and baroreflex sensitivity were calculated as indirect measures of cardiovascular autonomic health. Continuous data (median [95% confidence interval]) were analyzed with Mann-Whitney U tests or Kruskal-Wallis tests with Dunn's corrections. Patients with long-COVID had lower upright high frequency heart rate variability (p = 0.04) and low frequency blood pressure variability (p = 0.001) than controls. Patients with initial orthostatic hypotension had lower supine baroreflex sensitivity compared with patients without abnormalities (p = 0.01), and lower supine baroreflex sensitivity (p = 0.001) and high frequency heart rate variability (p = 0.03) than patients with postural orthostatic tachycardia syndrome. Patients with postural orthostatic tachycardia syndrome had lower upright high frequency heart rate variability (p < 0.001) and baroreflex sensitivity (p < 0.001) compared with patients without abnormalities and lower upright low frequency blood pressure variability (p = 0.04) compared with controls. Patients with long-COVID have attenuated cardiac autonomic function. Patients with initial orthostatic hypotension have lower supine baroreflex sensitivity. Patients with postural orthostatic tachycardia syndrome have lower upright vascular sympathetic and cardiac parasympathetic modulation. Long-COVID subgroups do not present with homogeneous pathophysiology, necessitating targeted treatment strategies.

Understanding the experiences of people who have postural orthostatic tachycardia syndrome (POTS) and the health professionals who care for them: a grounded theory study. Postural orthostatic tachycardia syndrome (POTS) is an under recognised, predominantly female condition. Awareness of this condition has increased due its association with Long-COVID. Understanding experiences informs areas for future study. Research into the experience of POTS is emerging, with no currently published studies including the experiences of health professionals. This study aimed to understand experiences of POTS, its challenges, and aspects of care from the perspectives of people with the condition and health professionals who look after them. A grounded theory approach was taken to develop a conceptual framework of the experience of POTS conceptualised through a critical realist lens. This United Kingdom based study included people with POTS from three national health care centres and a diverse range of health professionals. Theoretical and purposive sampling recruited people with POTS, and snowball sampling recruited health professionals through a United Kingdom charity and arrhythmia nursing network. Health professionals were interviewed from a range of professions including nurses, secondary care consultants, primary care general practitioners, psychologists, physiotherapists, and an occupational therapist. Between September 2021 and September 2022 in-depth online semi-structured interviews were undertaken. Data were thematically analysed. Corbin and Strauss' Grounded Theory methods of constant comparison, memos, and a reflexive journal were used. Analysis moved from first open coding of health professional themes to more focused axial coding, data, and category linking. The study patient and public involvement group informed thematic development and theoretical sampling. The final themes were conceptualised through the critical realism's three layers of experience. Forty-four participants were included, 19 people with POTS and 25 health professionals. Three core themes were found: 1) A challenging condition, 2) POTS healthcare provision - services by accident not design, and 3) The need to validate experiences. Health professionals experienced challenges in their clinical self-efficacy. POTS care was driven by individual human agency and interpersonal relationships. People with POTS took individual responsibility for their self-management but were impacted by gender inequalities, a medical model prioritising guidelines, and a poor evidence-base. This is the first qualitative study to explore both people with POTS and health professional experiences of looking after people with this condition. Findings identified: 1) a need for empowering both people with POTS and health professionals through shared care and decision making, 2) the requirement for a system wide recognition of POTS to move the landscape away from one of individual responsibility, and 3) the need to develop the evidence-base. Health Research Authority (IRAS: 281284). First recruitment: 13/09/2021. Understanding the experiences of people with POTS and the health professionals who see them. The findings of 44 in-depth interviews.