Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive orthostatic heart rate increase and lacks approved pharmacologic therapies. The objective of the study was to compare hemodynamic effects of ivabradine and propranolol and assess medication preferences in patients with POTS. In a randomized, placebo-controlled, crossover trial, patients with POTS completed three 4-week treatment phases (ivabradine, propranolol, and placebo). Each phase concluded with a 10-minute head-up tilt test with continuous beat-to-beat hemodynamic monitoring. Analyses included 28 participants (mean age 33 ± 9 years, 100% female). The prespecified primary outcome was delta heart rate during tilt. Head-up tilt test hemodynamics were described as minute-by-minute averages, deltas from supine baseline, and peak heart rate (HR) in the last 5 to 10 minutes. Prespecified within-participant comparisons were performed between treatments. Treatment preference was recorded at each phase end. Compared to placebo, HR was lower for ivabradine (99 ± 3 vs 118 ± 3 beats/min; P < 0.001) and propranolol (100 ± 3 vs 118 ± 3 beats/min; P < 0.001). ΔHR (standing - supine) was lower for ivabradine (27 ± 2 vs 36 ± 2 beats/min; P = 0.001) and propranolol (28 ± 2 vs 36 ± 2 beats/min; P = 0.003) vs placebo. Ivabradine showed a greater increase in Δ systolic blood pressure compared to propranolol (4.9 mm Hg vs 1.9 mm Hg; P = 0.001) but no significant difference in either HR or ΔHR between them. Among 22 preferences, all participants preferred ivabradine (P < 0.001) or propranolol (P < 0.001) over placebo, without differences between active treatments (59% vs 41%; P = 0.52). Ivabradine and propranolol reduce orthostatic tachycardia vs placebo, lowering heart rate below POTS diagnostic criteria. Ivabradine elevates systolic blood pressuremore than propranolol, supporting personalized drug selection. Importantly, heart rate lowering was consistent whereas symptom and quality-of-life effects were more selective, supporting individualized treatment.

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder that is often diagnosed after diagnostic delays due to reliance on heightened clinical suspicion. Hypermobility spectrum disorders (HSD) bridge the gap between asymptomatic joint hypermobility and hEDS. Due to overlapping features and evolving diagnostic criteria, these entities are often discussed collectively as hEDS/HSD. Patients commonly present with gastrointestinal (GI) symptoms, prompting referral for specialized care. This review summarizes the diagnostic criteria, epidemiology, and GI manifestations of hEDS/HSD to aid gastroenterologists in recognizing common presentations and facilitating earlier diagnosis and appropriate management. We conducted a narrative review of the GI manifestations of hEDS/HSD, including associations with disorders of gut-brain interaction (DGBIs), organic GI disease, structural abnormalities, motility disorders, postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). The strongest GI association in hEDS/HSD is with DGBIs. Evidence suggests possible associations with organic conditions, such as celiac disease and eosinophilic esophagitis, as well as structural GI abnormalities and dysmotility. In addition, hEDS/HSD is closely linked with POTS and MCAS, which may share pathophysiologic mechanisms and have synergistic effects on symptoms. Gastroenterologists should maintain a high index of suspicion for hEDS/HSD, which can be readily screened for using the Beighton score. Earlier diagnosis may be therapeutic by reducing uncertainty related to multisystem symptoms. A multidisciplinary approach incorporating mental health, nutrition, and pain management may be required to optimize patient outcomes.

Bowel and skin biopsies from patients with gastrointestinal disorders have revealed neuropathic changes and altered connective tissue. Patients with postural orthostatic tachycardia syndrome (POTS) often suffer from gastrointestinal symptoms and concomitant hypermobility spectrum disorders, such as hypermobile Ehlers-Danlos syndrome (hEDS). Since the skin is more accessible than the bowel, the aim of the present study was to evaluate skin biopsies in a 3D manner using micro-CT in patients with POTS and controls and relate the findings to symptoms presented. Healthy controls (n=13) and patients with POTS with (n=11) or without hEDS/EDS (n=26) were evaluated. Skin biopsies were taken proximally to the lateral malleolus using a 3 mm needle, fixed in formaldehyde and embedded in paraffin. The samples were harvested using a 1.5 mm punch (length, 2-5 mm) and scanned using a laboratory X-ray phase-contrast micro-CT. Scans were evaluated in a blinded manner and the regularity, thickness and tightness of collagen fiber bundles were assessed. All dermal structures were visible without staining. Intraepidermal nerves were not visible and a number of cell types could not be separated. The percentage of disorganized collagen bundles differed between groups, due to the majority being disorganized in hEDS/EDS (P=0.030). The proportion of any disorganized and parallel bundles throughout the biopsy differed within both patient groups (P<0.001) but not within the control group (P=0.175). There were no differences in symptoms between participants with disorganized bundles and participants without disorganized bundles. In conclusion, X-ray phase-contrast micro-CT was suitable to visualize and characterize dermal skin components in 3D. Patients with POTS and hEDS/EDS exhibited more disorganized collagen bundles; however, the technique cannot currently be used for diagnostic purposes until more patients are examined.

What is the clinical question being addressed? What are the clinical and hemodynamic differences between postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia? What is the main finding? Inappropriate sinus tachycardia exhibits higher rates of hypertension, whereas postural orthostatic tachycardia syndrome and dual pathology exhibit higher rates of presyncope, cognitive impairment, and nausea.

Mast cell activation syndrome (MCAS) is a challenging specialized condition that allergists-immunologists treat in the outpatient setting. Despite the wide prevalence of the disease, clinicians may feel overwhelmed to provide consistent compassionate care for these patients for a multitude of reasons. Patients uniformly describe feeling unheard during a clinical encounter and thereby often end up seeing multiple physicians and specialists which further complicates their medical care. As such, it is important to characterize patients with MCAS accurately, which includes the assessment of coexistent mimicking or confounding conditions to achieve best medical care outcomes.

Postural orthostatic tachycardia syndrome (POTS) is a chronic autonomic disorder associated with debilitating symptoms. No medications have been approved for treatment, and patients commonly use off-label medications to treat symptoms. The hemodynamic implications of certain medication use have been examined, but patient experiences with taking off-label medications are underreported. A qualitative descriptive study was conducted with 13 patients (all women; aged 38 ± 13 years) diagnosed with POTS who had taken off-label medications for their symptoms. Semistructured video interviews were conducted to explore how they experienced and perceived their medication use. Interviews were recorded, transcribed, and analyzed using conventional content analysis. Most patients described medications as being beneficial and life-altering, re-enabling basic activities, work, exercise, and social engagement. All patients intended to continue therapy. Side effects were common but generally manageable. Propranolol frequently was associated with fatigue and hypotension. Ivabradine often caused transient early headaches and visual symptoms that subsided. Dosing frequency was largely acceptable. Major barriers included the following: medication cost, especially for ivabradine when patients were not insured; limited clinician awareness of POTS; diagnostic delays; and uncertainty about long-term safety. Medications provide meaningful functional improvement for many patients, but treatment burden, financial barriers, and information gaps persist. Care should prioritize individualized, patient-centred prescribing, and shared decision-making. Additional research should compare common medications to increase exposure and evaluate long-term outcomes and access.

One of the most common complaints in ENT clinics is dizziness. Although most cases are caused by vestibular neuritis and benign paroxysmal positional vertigo (BPPV), a significant number of patients experience non-vestibular dizziness. One non-vestibular cause is postural orthostatic tachycardia syndrome (POTS), which presents with symptoms similar to vestibular migraine (VM) and persistent postural perceptual dizziness (PPPD). Dizziness from POTS is related to dysautonomia rather than the vestibular system. In otolaryngology, understanding the autonomic nature of non-vestibular dizziness is important for accurate diagnosis. This study aims to review the clinical characteristics and pathophysiology of POTS, vestibular migraine, and PPPD; examine historical, physical, and diagnostic findings that differentiate autonomic and vestibular causes of dizziness; and develop a more specific model for evaluating chronic dizziness in the ENT setting. Literature on dizziness, vestibular and autonomic pathophysiology, and the clinical presentation of POTS, VM, and PPPD is reviewed in this paper. The timing of symptoms, their triggers, and objective assessment are key differentiating factors for these disorders. Various diagnostic tools, including orthostatic vital signs, oculomotor assessment, gait and balance evaluation, vestibular function assessment, tilt table testing, and neuroimaging, are also reviewed. Clear distinctions among POTS, VM, and PPPD are made. The diagnostic criteria for POTS are orthostatic tachycardia and posture-dependent symptoms that improve when the patient is in a recumbent position, effectively ruling out vestibular involvement in these patients. Vestibular migraine presents with vertigo accompanied by migraine features such as photophobia, phonophobia, or headache, typically triggered by sensory or environmental factors rather than changes in posture. PPPD manifests as chronic non-spinning dizziness and imbalance lasting at least three months, exacerbated by motion, upright posture, and complex visual environments. Orthostatic vital signs and autonomic assessment should be included in the evaluation of patients presenting with dizziness to differentiate between these disorders. Both vestibular and autonomic dysfunction can lead to chronic dizziness. By incorporating autonomic assessments into vestibular evaluations, ENT physicians can apply a more precise diagnostic model for their patients. Identifying dysautonomia-related dizziness, including POTS, helps reduce the misdiagnosis of vestibular disorders. This approach enables physicians to provide more effective interventions for patients with complex dizziness.

: Patients with postural tachycardia syndrome (POTS) commonly experience gastrointestinal (GI) symptoms. We aim to assess the feasibility and preliminary efficacy data for DA-9701, a prokinetic agent targeting 5-hydroxytryptamine 1A, 5-hydroxytryptamine 4, and dopamine D receptors, in patients with POTS. : In a randomized, double-blind, placebo-controlled, single-center crossover trial, patients with POTS were given either 30 mg of DA-9701 or a placebo 3 times daily for eight weeks in a 1:1 ratio. After a 4-week washout, patients received the alternate treatment for another 8 weeks. The primary endpoint focused on assessing the change in GI symptoms (total Nepean Dyspepsia Index-Korean version [NDI-K] symptom score) from baseline over the 8 week-treatment period. Endpoints were assessed in all enrolled and randomized patients (intention-to-treat), and in those who completed the trial (per-protocol analysis). : Between January 2022 and August 2023, 24 patients were randomized (n = 12 per group), with 3 discontinuing after randomization. DA-9701 did not significantly improve primary endpoints for total NDI-K symptom scores in either the intention-to-treat (least-squares means, -13.9 vs. -9.5, = 0.326) or per-protocol analyses (-17.2 vs -12.0, = 0.242). Notably, a trend toward improvement in specific GI symptoms, such as upper abdominal pain, was observed in both intention- to-treat (-0.6 vs 0.7; = 0.066) and per-protocol analyses (-0.9 vs 0.6; = 0.045). No serious adverse events were observed. DA-9701 did not improve GI symptoms in this crossover trial; however, its potential effect on specific GI symptoms merits further investigation.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.