Muscle sympathetic nerve activity (MSNA) is valuable for POTS management, but microneurography is clinically impractical. We investigated whether the Valsalva phase 2 diastolic blood pressure rise (DBP) could be a surrogate for MSNA during the Valsalva and be used to identify hyperadrenergic POTS. We included 21 POTS females and 22 healthy females 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 equal 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 ± 10vs105 ± 12 mmHg, p = 0.026), shorter pressure recovery time (1.15 ± 0.75vs2.59 ± 1.17 s, p = 0.005), and higher psNVT (2.60 ± 1.02vs0.58 ± 0.46 mmHg/spike•s, p < 0.001) than the non-hyperadrenergic POTS. DBP ≥ 15 mmHg could be a marker of hyperadrenergic response to subtype POTS. We defined this subset of POTS as functional hyperadrenergic POTS since they displayed hyperadrenergic phenotypes despite similar level of MSNA to other POTS. The higher psNVT of the hyperadrenergic group suggested a novel pathophysiology of enhanced neurovascular coupling.

The autonomic nervous system and the gastrointestinal (GI) system share a bidirectional relationship. Clinically, disruptions to either of these systems mutually influence the onset and persistence of symptoms modulated by the other system. The impact of autonomic dysfunction on GI health is especially relevant in the care of pediatric disorders of gut-brain interaction (DGBI) as these patients commonly report a diverse range of symptoms both within and outside the GI tract. Therefore, it is essential to include the role of autonomic function in the assessment and treatment of pediatric patients with DGBI.

Syncope is a temporary loss of consciousness due to cerebral hypoperfusion associated with autonomic dysfunction. Vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) are the most common causes of syncope in adolescents. Here we conducted a comparative analysis of VVS and POTS in adolescents using transcranial doppler (TCD) and autonomic function tests to identify the mechanisms underlying the occurrence of each. From August 2014 to July 2024, a tilt-table test was conducted on patients who presented with syncope or presyncope as the main symptom. Based on the head-up tilt test results, the patients were classified into the VVS or POTS groups and their medical records retrospectively analyzed. The study included 137 patients: 100 (73%) in the VVS group and 37 (27%) in the POTS group. There were no significant intergroup differences in patient characteristics. In the TCD, the diastolic blood flow velocity during symptom onset was significantly lower in the VVS versus POTS group (18.40±7.14 cm/sec vs. 22.32±8.48 cm/sec, P=0.008). Additionally, the pulsatility index was higher in the VVS group (1.51±0.41 vs 1.22±0.37, P<0.005). There were no intergroup differences in autonomic function tests results or composite autonomic severity scores. The cerebral blood flow velocity during diastole differs between VVS and POTS, suggesting that it may be a determining factor in the pathogenesis of each.

Our previous studies demonstrated that the regular practice of recumbent isometric yoga reduced the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Some patients with ME/CFS have postural orthostatic tachycardia syndrome (POTS); however, the effects of recumbent isometric yoga on orthostatic cardiovascular responses and whether recumbent isometric yoga improves POTS remain unknown. This pilot study was done to investigate the effect of recumbent isometric yoga on the orthostatic cardiovascular response of patients with ME/CFS. Ten adult female patients with ME/CFS performed recumbent isometric yoga for 12 weeks. Changes in their systolic blood pressure (SBP), diastolic blood pressure (DBP), and the pulse rate (PR) during an active standing test were compared before and after the 12-week regimen. Among the 10 patients, 8 manifested a normal orthostatic response and 2 manifested POTS before the yoga intervention. Patients who manifested a normal orthostatic response before yoga also manifested the normal orthostatic pattern after the yoga intervention. In contrast, the two patients who manifested POTS before the regimen showed a normal orthostatic response after completing the yoga intervention. This study found that the patients who manifested POTS and performed recumbent isometric yoga for 12 weeks had a reduced increase in PR after standing up. This pilot study suggests that recumbent isometric yoga would be useful as an adjunctive nonpharmacological intervention for improving POTS in patients with ME/CFS. This finding should be confirmed in a larger number of cases.

With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is now widely recognized for causing several long-term effects known as post-COVID-19 syndrome (PCS) or long COVID (LC). This presents a growing challenge for healthcare systems worldwide. This narrative review summarizes original peer-reviewed studies indexed in PubMed and published between January 2020 and August 2025. It focuses on adult populations unless stated otherwise. We included studies that provided primary clinical or imaging data on chronic cardiovascular outcomes after confirmed SARS-CoV-2 infection. We excluded case reports, pediatric-only cohorts, and non-peer-reviewed sources. Among the various cardiovascular issues related to LC, we focused on heart fibrosis (HF), postural orthostatic tachycardia syndrome (POTS), new-onset hypertension (HT), and coagulopathy. These conditions consistently show up in the reports and are significant in terms of illness, potential long-term disability, and public health impact. Although these issues are distinct in their underlying causes, they share common mechanisms. These include ongoing inflammation of the endothelium, disruption of the renin-angiotensin-aldosterone system (RAAS), immune-related tissue damage, and an ongoing state that promotes blood clots. These processes can lead to measurable myocardial fibrosis that cardiac magnetic resonance imaging can detect, autonomic dysfunction often seen as POTS, a greater risk of developing hypertension shortly after infection, and a long-term rise in thromboembolic events due to increased clotting and resistant microclots. Current management is mostly focused on relief of symptoms and involves a team approach. It uses repurposed medications and tailored physical rehabilitation since no specific cure is available yet. Promising but still experimental methods, such as endothelial-protective agents like sulodexide and targeting inflammatory pathways, need thorough testing. There are significant gaps in our understanding of the long-term risk of hypertension, the natural progression of fibrosis, and the best treatment for POTS. This highlights urgent needs for future research. Beyond caring for individual patients, these ongoing cardiovascular problems raise important public health concerns. They include higher healthcare use, long-term disability, and economic costs. This situation requires increased clinical attention and proactive cardiovascular monitoring for those recovering from COVID-19.

Microneurography studies showed that the alpha-2 agonist clonidine suppresses sympathetic nerve activity. However, clonidine's neuromodulation effects in ambulatory patients are unknown. To test the hypothesis that clonidine suppresses skin sympathetic nerve activity (SKNA) and decreases heart rate (HR) in patients with hyperadrenergic postural orthostatic tachycardia syndrome (POTS). This prospective observational study included 33 patients with POTS treated with clonidine. We recorded ambulatory neuECG for 24 hours before clonidine and 3 days afterward. A follow-up recording was done 6 months later. Symptomatic episodes were documented by diary and button press. Overall, 26 participants (24 women) completed the first recording. Ten participants (38%) completed the follow-up recordings and experienced fewer symptomatic episodes (P = .030) and lower 24-hour average HR (P = .020) at follow-up than at baseline. The ratio of low frequency and high frequency SKNA significantly decreased on days 1-3 (P = .001, P <.001, and P <.001, respectively). SKNA burst frequency was significantly reduced on days 1 (P = .010) and 2 (P = .012). The 24-hour average HR decreased significantly on days 1-3 (P = .005, P <.001, and P <.001, respectively). The maximum HR during the day also significantly decreased on day 2 (P = .043) and day 3 (P <.001). Eleven had sympathetic toggled sinus rate acceleration episodes. Sinus rate acceleration burden and duration decreased in 7 of 11 patients (64%). In 3 participants, clonidine induced episodic bradycardia and sinus arrhythmia. In hyperadrenergic POTS, clonidine reduced SKNA and the low frequency/high frequency ratio. Ten participants (38%) used clonidine for > 6 months, and most (8/10, or 80%) had fewer symptoms than at baseline.

Postural tachycardia syndrome (POTS) is a complex autonomic disorder with growing evidence suggesting an autoimmune contribution in a subset of patients. Therapeutic plasma exchange (TPE) is known as a potential treatment option, particularly for patients with severe or refractory disease. This editorial summarizes the clinical features of POTS, the pathophysiologic rationale for plasma exchange, and the current evidence supporting its use. Although encouraging, there is a need for larger studies and standardized protocols. Further research is warranted to clarify patient selection, treatment regimens, and long-term outcomes.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate increase upon standing, often associated with dizziness, gastrointestinal symptoms, and decreased functional capacity. Acute hepatic porphyrias (AHP) are rare metabolic disorders with nonspecific neurovisceral and autonomic symptoms, some of which overlap with POTS. The purpose of this study was to evaluate AHP by molecular and biochemical testing in patients with POTS. We studied 50 patients diagnosed with POTS and gastrointestinal symptoms at the Vanderbilt Autonomic Dysfunction Center. They underwent neuro-hormonal evaluation for POTS and genetic and biochemical screening for AHP. Genetic testing was aimed mainly at the four genes relevant to AHPs. Porphobilinogen (PBG), delta-aminolevulinic acid (ALA), and total porphyrins were measured in urine with normalization to creatinine. The average age of the patients was 33 ± 8.6 years, 96% were female, and the average BMI was 28 ± 7.2 kg/m, average systolic blood pressure was 120 ± 15.5 mmHg, average heart rate was 77 ± 13.6 bpm at baseline, and average SBP was 126 ± 19.1 mmHg. A heart rate of 111 ± 15.8 bpm at 10 min upright, showed normal cardiovascular reflexes. The COMPASS-31 total score was 32 ± 8.4, with a normal autonomic function test. Urine PBG averaged 1 ± 0.7 mg/g creatinine, ALA 2 ± 0.9 mg/g creatinine, and total porphyrins 172 ± 74.2 mmol/g creatinine, which were all normal. None had variants in the four genes associated with AHPs. Three patients were heterozygous for a common low expression ferrochelatase gene variant (FECH). We found no evidence of AHP in patients with POTS with uncontrolled gastrointestinal symptoms, suggesting that screening for AHP, a rare genetic disorder, may not be warranted.

: Patients with inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) exhibit complex clinical profiles due to autonomic dysfunction. While sinus node sparing (SNS) hybrid ablation is emerging as a promising therapy, there are no established guidelines worldwide for post-procedure patient management and care is mainly based on telemonitoring. In contrast, our hybrid cardiac rehabilitation (HCR) program integrates inpatient care and home-based telerehabilitation. We aim to evaluate the implementation of the HCR program, patient acceptance and adherence, and the effectiveness of the Malmö POTS scoring system in monitoring disease progression and rehabilitation outcomes. : Patients underwent a personalized HCR program after SNS. The program included early mobilization, psychological support, respiratory therapy, and structured exercise. Clinical outcomes were assessed using symptom burden (Malmö POTS score), ECG parameters, exercise duration, perceived exertion, and rehabilitation adherence. All patients completed the inpatient phase, and 87% completed the home-based phase. In the early postoperative period, pericarditis, anemia, and benign rhythm disturbances were mild and self-limiting. The Malmö POTS score decreased from 65.3 to 25.7. Lower perceived exertion early in the program correlated with clinical improvement. At the 2-month follow-up, 81% of patients no longer met the clinical criteria for IST/POTS without the use of medications. The program was evaluated as safe, feasible, and well-tolerated, with high patient satisfaction. : A well-organized hybrid cardiac rehabilitation program after SNS is feasible, safe, and well-tolerated in IST/POTS patients. The Malmö POTS score may support outcome monitoring. The integration of individualized training and telemedicine represents a promising development for patients post-SNS ablation. While this study demonstrates feasibility and potential benefits, further controlled studies are needed to evaluate its impact on long-term recovery and symptom control.

Hypermobile Ehlers-Danlos syndrome (hEDS) affects multiple systems, but comprehensive evaluations of a larger sample of hEDS patients are lacking. The objective of this study was to describe cerebrovascular, autonomic, and neuropathic features of hEDS. This retrospective case-control study was conducted at Brigham and Women's Faulkner Hospital between 2016-2023. Data from hEDS patients who completed autonomic testing and skin biopsies were analyzed. Outcome measures include validated surveys (Survey of Autonomic Functions, Neuropathy Total Symptom Score-6 (SAS)) and autonomic function testing (Valsalva maneuver, deep breathing, head-up tilt and sudomotor), cerebrovascular (cerebral blood flow velocity (CBFv) in the middle cerebral artery), respiratory (capnography), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/ autoimmune markers. Total 270 hEDS patients were analyzed and compared to 29 healthy controls. Common hEDS complaints (prevalence > 90% ) were orthostatic sudomotor, vasomotor, gastrointestinal, and pain. Orthostatic cerebral blood flow velocity was reduced in 79% of hEDS and correlated with orthostatic dizziness. The head-up tilt test revealed postural tachycardia syndrome (prevalence 33%), hypocapnic cerebral hypoperfusion (22%), orthostatic cerebral hypoperfusion syndrome (18%), and neurogenic orthostatic hypotension (9%). Widespread but mild autonomic failure was present in 90% of hEDS patients on autonomic testing. Small fiber neuropathy using structural criteria was detected in 64%, and using combined structural and functional criteria in 82%. This study provided evidence of cerebrovascular dysregulation with reduced orthostatic cerebral blood flow velocity associated with symptoms of cerebral hypoperfusion, frequent small fiber neuropathy, and widespread but mild autonomic failure in hEDS.

Individuals recovering from COVID-19 infection have reported experiencing symptoms of postural orthostatic tachycardia syndrome (POTS). These observations have raised concerns about COVID-19 as a significant precipitating factor in the development of post-viral POTS. Given the increasing number of POTS cases reported after COVID-19, we sought to examine the baseline characteristics of POTS patients before and after COVID-19. We conducted an interrupted time series analysis on data obtained from the TriNetX database, which included a cohort of 65 141 065 patients aged 18 and older across 64 healthcare organizations. Monthly data on incidence rates (IR), incidence cases (IC), and prevalence cases (PC) of POTS were collected from January 2018 to June 2024, with 1 March 2020 defined as the cutoff date for pre- and post-COVID analysis. There was a significant increase in the IR of POTS post-COVID (P < 0.0001), with the IR increasing from 1.42/1000 000 to 20.3/1000 000 cases per person-year. Similarly, the monthly IC trend showed a significant rise from 4.21 to 22.66 cases (P < 0.001). The month-to-month prevalence showed an initial decline after COVID with a robust increase starting January 2023. Additionally, the prevalence of autonomic nervous system disorders and related comorbidities significantly decreased in the post-COVID cohort. Our findings demonstrate a significant increase in the incidence of POTS following the COVID-19 pandemic, suggesting a potential association between COVID-19 infection and the development of post-viral POTS. Future research should explore the underlying mechanisms and treatment strategies for POTS in the context of post-COVID recovery.

Postural Orthostatic Tachycardia Syndrome (POTS) patients experience debilitating symptoms and struggle to obtain a timely diagnosis. Mobile health (mHealth) and wearable technology may provide health information to empower patients when communicating with providers and in turn shorten the time to diagnosis. We conducted three online co-design focus groups with POTS patients to determine elements of a desirable mHealth intervention. Themes emerged that helped us develop a smartphone- and wearable-based system, using a risk communication model as a message design framework. A pilot randomized trial is ongoing to test the POTS App. Initial results showed the app reaches high usability.

The objective is to compare the frequency and clinical characteristics of pediatric Postural Orthostatic Tachycardia syndrome (POTS) diagnoses before and during the Coronavirus Disease 2019 (COVID-19) pandemic and assess potential contributing factors. This retrospective study analyzed 117 pediatric patients diagnosed with POTS between January 2018 and December 2023 at a single tertiary center. Patients were divided into pre-pandemic (n = 46) and pandemic (n = 71) groups. Clinical, laboratory, and psychosocial data were collected and compared. Logistic regression was used to identify independent predictors of pandemic-period diagnoses. A significant increase in POTS diagnoses was observed during the pandemic (10.5% vs. 6.1%, P= .01). Pandemic-period patients reported lower physical activity (72%) and higher screen time (85%), with increased symptoms of anxiety (34% vs. 18%, P= .04) and palpitations (P= .03). Vitamin B12 levels were higher in the pandemic group (P= .043), while hemoglobin levels and heart rate variability remained similar across groups. The COVID-19 pandemic was associated with a marked rise in pediatric POTS diagnoses, likely driven by lifestyle alterations and psychosocial stress rather than nutritional deficiencies. These findings underscore the importance of early recognition, physical reconditioning, and psychological support in managing POTS, particularly during global health crises.

Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID. The purpose of this study was to describe the experience of people reporting long COVID-associated POTS. We collected data from individuals aged ≥18 years with self-reported long COVID who participated in the Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) cohort, an online observational study. The study included participants surveyed from May 2022 to July 2023. POTS status was determined by self-reported diagnosis of POTS. We compared the demographics, symptoms, associated conditions, and health status of people with and without self-reported POTS. Of the 578 individuals included, 167 (28.9%) reported new-onset POTS and 411 (71.1%) did not report POTS as one of their long COVID-associated conditions. Seventy-eight percent of participants with self-reported POTS were women (range, 18-74 years). Participants with self-reported POTS were younger, had more financial difficulties, more social isolation, more suicidal thoughts, worse health status measured by the EuroQoL visual analog scale, and reported higher rates of rapid heart rate after standing up, dizziness, palpitations, persistent chest pain, sudden chest pain, excessive fatigue, exercise intolerance, heat intolerance, brain fog, tinnitus, migraine, internal tremors, skin discoloration, and dry eyes, as well as new-onset myalgic encephalomyelitis/chronic fatigue syndrome and mast cell disorders. Individuals with self-reported long COVID-associated POTS experienced substantial health burdens in various domains compared with those without self-reported POTS, highlighting the urgency for further research to understand the mechanism, characterize the physiological derangements, and target treatments so we can help these individuals.

Pregnancy in women with Ehlers-Danlos syndrome (EDS) carries elevated risks, including prematurity, hemorrhage, and maternal morbidity, posing significant anesthetic challenges. We present the case of a 36-year-old woman with classical EDS (cEDS) and multiple comorbidities, including postural orthostatic tachycardia syndrome, bronchial asthma, congenital adrenal hypoplasia, and chronic venous thrombosis, who underwent an elective cesarean section. A multidisciplinary team developed a comprehensive perioperative plan featuring ultrasound-guided spinal anesthesia, extended post-anesthesia observation, and coordinated recommendations from cardiology, hematology, endocrinology, pulmonology, and other specialties. This report emphasizes the complexity of anesthetic care in EDS pregnancies and underscores the need to tailor management to the specific EDS subtype and individual patient profile.

Lyme disease is a leading vector‑borne illness in the United States, and its geographic range has been expanding into the Midwest, including Michigan. Although Lyme carditis is an uncommon complication, it can produce rapidly progressive atrioventricular (AV) conduction disturbances, including complete heart block, that mimic intrinsic cardiac disease and may lead to unnecessary permanent pacemaker implantation if not recognized. We describe a 19‑year‑old woman with a history of postural orthostatic tachycardia syndrome who presented with headache, nausea, vomiting, palpitations, chest discomfort, and bilateral arm paresthesias. She had recently recovered from an upper respiratory infection but denied rash or focal deficits. On presentation, she was bradycardic and borderline hypotensive, and an electrocardiogram showed complete heart block. Laboratory testing revealed elevated inflammatory markers and cardiac biomarkers. She required a temporary transvenous pacemaker and was admitted for management. Lyme serology returned positive, and intravenous ceftriaxone therapy was initiated. Over several days, her AV conduction improved from complete heart block to first‑degree block and ultimately to normal sinus rhythm. The temporary pacemaker was removed, and she completed a course of intravenous antibiotics at home via a peripherally inserted central catheter. This case illustrates the reversible nature of high‑degree AV block caused by Lyme carditis. Early recognition of the condition in young patients with unexplained conduction abnormalities in tick‑endemic areas enables appropriate antimicrobial therapy and avoids unnecessary permanent pacing.

Individuals with postacute COVID-19 syndrome (PACS) typically exhibit abnormal hemodynamic responses during upright positioning, including orthostatic hypotension and postural orthostatic tachycardia syndrome. The 10-minute NASA lean test (NLT) has been suggested for this condition. However, no comparative study with the head-up tilt table test (HUTT) has been conducted. This study aimed to compare blood pressure and heart rate responses during the 10-minute duration of NLT and HUTT. Eighty young individuals (aged 22.0 ± 3.1 years) with PACS underwent both tests, with a 30-minute interval between tests. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured every minute, and the differences between supine and upright positions were analyzed. There were no significant differences in SBP changes between HUTT and NLT (-7.8 ± 6.2 vs. -7.1 ± 7.5 mmHg) with a mean difference of -0.7 ± 9.0 mmHg. However, DBP changes were significantly lower in HUTT compared to NLT (-0.9 ± 6.4 vs. 1.5 ± 6.9 mmHg for NLT) with a mean difference of -2.4 ± 7.1 mmHg. Maximal HR was significantly lower in HUTT compared to NLT (92.0 ± 11.4 vs. 96.2 ± 10.8 bpm for NLT) with a mean difference of -4.2 ± 6.9 bpm. Additionally, HR changes were significantly lower in HUTT compared to NLT (21.5 ± 8.1 vs. 27.0 ± 9.0 bpm) with a mean difference of -5.4 ± 6.4 bpm. The NLT demonstrated comparability with the HUTT in detecting SBP changes. However, clinical applications should consider differences in measuring DBP and HR changes.

To provide pediatric providers with the most up to date information on evaluation, diagnosis, and treatment of orthostatic intolerance and postural orthostatic tachycardia syndrome (POTS). In this review, new research is summarized on the importance of exercise, the role of anxiety and depressed mood in exacerbating symptoms, and medication utilization. Orthostatic intolerance and POTS are increasingly common causes of significant infirmity during adolescence. Pediatricians are front line in implementing treatment, which is centered on patient education and nonpharmacologic strategies. Precise history taking identifies the conditions, and accurately explaining the pathophysiology to families encourages patient buy-in to follow a rigorous treatment program. While anxiety and depressed mood are not central causes of symptomatology, they do exacerbate a patient's presentation and thus must be treated aptly. Prognosis is excellent in patients who adhere to a treatment plan, and encouragement from providers as to this expectation is key to building a strong therapeutic alliance.

Head-up tilt (HUT) and active stand tests (AST) are used in the diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS), but their relative diagnostic accuracy is unclear. This necessitates a direct comparison under standardized conditions. We aimed to compare the hemodynamic responses and diagnostic accuracy of AST vs. HUT in POTS. To address this, patients with POTS (n = 60) completed a 10-min AST followed by HUT on the same day. Beat-to-beat hemodynamics were recorded during 10-min supine baselines and each test. Delta values were calculated for each test (upright 1-min averages minus baseline average). Δ[heart rate] increased significantly over time (1_Min: 28 bpm to 10_Min: 40 bpm; P < 0.001), and was greater for HUT (33 bpm vs. 37 bpm; P = 0.01), with significant Time x Condition interaction (38 bpm vs. 42 bpm at10min; P < 0.001). Δ[stroke volume] declined over time (1_Min: -18 ml to 10_Min: -32 ml); P < 0.001), with no significant test or interaction effects (P = 0.36; P = 0.21). Δ[SBP] decreased (1_Min: -0.3 mmHg to 10_Min: -5.7 mmHg); P < 0.001) over time, with no test or interaction effects. Fewer patients met POTS heart rate criteria during the AST (AST: 74 % vs. HUT: 98 %; p < 0.001). Lowering the threshold to 27 bpm for AST narrowed the gap but was still significantly higher for HUT (AST: 83 % vs HUT: 98 %; p = 0.02). Orthostatic tachycardia differs between AST and HUT in patients with POTS. The proportion of patients with POTS meeting the heart rate diagnostic criteria differs significantly between AST and HUT, a discrepancy that can be mitigated by lowering the heart rate threshold for the AST.

Sympathetic function is directly assessed by microneurography measuring muscle sympathetic nerve activity (MSNA). The recordings are typically corrupted with noise and require denoising. We aim to estimate microneurographic noise individually from physiologically suppressed MSNA during Valsalva phase 4 (VM4). We developed MSNA adaptive processing (MAP). MSNA recordings during Valsalva were transformed by stationary wavelet transformation. Level-specific noise thresholds were computed from 4 SD of detail coefficients from VM4 and were implemented for denoising. The denoised signals were inverse transformed, then the MSNA spikes were detected. We compared detection performance of the MAP with the current two-stage kurtosis method in simulated MSNA signals, and recordings from 17 healthy and 19 postural orthostatic tachycardia syndrome (POTS) female subjects performing Valsalva. The MAP had higher correct detections of MSNA spikes than the kurtosis method in simulated signals wit high burst rate (50 burst/min) and low signal-to-noise ratio (SNR =2) (MAP vs kurtosis; 23.81 ± 15.49 % vs 16.98 ± 12.75 %, p < 0.001). The improvement was confirmed by shorter error distance of the precision-recall plot (0.535 ± 0.175 vs 0.542 ± 0.177, p = 0.011). The MAP detected higher spike rate during VM phase 2 in healthy (24.11 ± 9.85 vs 19.57 ± 8.60 spike/s, p = 0.049), but non-significant in POTS (24.19 ± 13.70 vs 20.30 ± 11.85 spike/s, p = 0.101). The detection performance of the MAP is superior to the current two-stage kurtosis method. The proposed MAP method individually estimating noise from VM4 could improve MSNA spike detection, compared with the kurtosis method. The advantages are most prominent in high burst rate and low SNR MSNA recordings.

Thoracic outlet syndrome (TOS) is characterized by compression of nerves or blood vessels as they pass through the scalene triangle and the costoclavicular space, and under the pectoralis minor. Common symptoms include arm fatigue and heaviness, paresthesias, and neck and upper back pain, provoked by arm extension or elevation. We have recently reported that some myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients report symptoms suggestive of TOS, specifically with respect to overhead activity, but there is uncertainty whether this overlap in symptoms is more related to ME/CFS itself or a direct contribution by TOS. This case report describes an ME/CFS patient diagnosed with TOS, who experienced major decreases in many expected and unexpected symptoms after bilateral TOS surgery. A 19-year-old female patient with ME/CFS and the hypermobile Ehlers-Danlos syndrome (hEDS) developed progressive symptoms of numbness and tingling in the upper limbs, which did not improve after two months of physical therapy. The patient elected to undergo the rib resection with neurolysis and scalenectomy surgery on her left side. Due to the success in the reduction of symptoms, she elected to undergo the same procedure on the right side three months later. By eight weeks after the second surgery, the patient had experienced an expected complete resolution of upper limb numbness and tingling. She also reported a complete resolution of migraines, occipital neuralgia, vertigo, and visual disturbances, along with a marked improvement in cognitive fogginess and lightheadedness. This case report highlights the potential for marked improvements in clinical function after recognition and surgical treatment of TOS in a patient with comorbid hEDS and ME/CFS. In addition to expected improvement in upper limb symptoms and the resolution of occipital headaches, our patient noted improvement in systemic symptoms of lightheadedness, cognitive dysfunction, and visual disturbances. This experience suggests that those with hEDS and ME/CFS should be more carefully screened for brachial plexus dysfunction. Conversely, ascertainment of systemic symptoms may enhance the diagnosis of TOS and the items assessed in surgical treatment outcome studies.

Long-COVID describes a variety of COVID-19 side effects lasting longer than three months. Among these side effects are cardiovascular alterations, such as Postural Orthostatic Tachycardia Syndrome (POTS), caused by an autonomic nervous system dysfunction. A higher incidence of POTS and decreased baroreceptor sensitivity (BRS) has been reported in Long-COVID patients. Many of these patients present orthostatic intolerance similar to that observed in POTS, which does not strictly coincide with the criteria that have previously been established for POTS subtypes. Therefore, we aim to determine if the decrease of the baroreceptor sensitivity is enough to diagnose different degrees of the autonomic dysfunction spectrum. A cross-sectional study was conducted in a cohort of individuals who presented with various long-term symptoms for at least four weeks after a moderate acute COVID-19 infection. To further evaluate orthostatic intolerance (OI), we developed a new method that enables a more detailed characterization of cardiovascular dynamics using beat-to-beat physiological time series. Since these dynamics can be assessed through the measurement of baroreceptor sensitivity, this new method employs a geometric analysis that reveals varying degrees of baroreceptor sensitivity impairment. The proposed method generated a graph of baroreflex sensitivity that consistently showed a decrease in this index. Patients exhibited significantly lower BRS compared with healthy controls during orthostatism. Furthermore, we noticed that patients with lower BRS had a significantly higher arterial blood pressure and heart rate, as well as an overall lower heart rate variability. The proposed method also correlated with previously recognized canonical variables of HRV, as well as being validated with the sequence method. Additionally, this allows us to understand and reclassify patients' diagnoses within the spectrum of symptoms similar to postural orthostatic tachycardia syndrome (POTS). The proposed method allowed us to consider this decrease in baroreflex sensitivity measurement as a diagnostic tool through a spectrum-based approach to reclassify patients. This analysis can be incorporated into the set of variables considered to improve the diagnosis of patients with Long-COVID.

This prospective, cross-sectional study aimed to identify sex-based differences in diagnostic and symptom experiences in postural orthostatic tachycardia syndrome (POTS). Data from participants ≥ 16 years with physician-confirmed POTS enrolled in the Australian POTS registry between 1 May 2021 and 30 April 2024 were analysed. Health-related quality of life was assessed using the EuroQol 5 Dimension tool. Composite autonomic symptom score (COMPASS-31) assessed autonomic symptom burden. Self-reported sociodemographic and diagnostic journey data informed diagnostic experiences. In total, 452 females (mean age 31.4 ± 11.4 years) and 48 males (mean age 31.1 ± 14.6 years) were included. Females experienced worse autonomic symptom burden (total COMPASS-31; 50.5 ± 13.7 vs. 42.4 ± 16.4 for men; P < 0.001). Both sexes interacted with an equivocal number of doctors (P = 0.763) and emergency departments (P = 0.830) before diagnosis. Females had significantly longer diagnostic delays than men (7.0 ± 8.6 vs. 3.8 ± 5.4 years; P = 0.010) and were 1.2.7 times more likely to experience ≥10 years of diagnostic delay (95% CI; 1.1-6.6). Despite the diagnostic latency and worse symptom burden, females reported similar, anxiety, depression, and health-related quality of life to men (global health rating where '100' = full health; females, 46.2 ± 20.4 vs. males, 43.7 ± 23.6; P = 0.485). Females and males with POTS experience significant differences in autonomic symptom burden and diagnostic delay. These differences do not seem to arise from sex-based variations in health-seeking behaviour or symptom reporting but rather indicate the influence of clinician-dependent factors. Further research is needed to explore how clinician attitudes may impact sex-dependent differences in diagnosis and treatment outcomes for those with POTS. ANZCTR:12621001034820.

Postural orthostatic tachycardia syndrome (POTS) is a disorder characterized by orthostatic intolerance, tachycardia, and syncope. Ivabradine, though not Food and Drug Administration approved for POTS, has shown promise in its management. A 20-year-old woman with POTS, complicated by multiple comorbidities, experienced a severe functional decline. Standard therapies were ineffective. Given the presence of apical trabeculations and severe tachycardia, ivabradine was initiated, leading to rapid and sustained improvements in her symptoms. This case highlights the effectiveness of ivabradine in patients with complex POTS who have failed conventional treatments. The patient's dramatic recovery underscores its potential to enhance quality of life. While previous studies support the efficacy of ivabradine in treating POTS, this case reinforces it as a viable treatment option and adds real-world evidence for its inclusion in treatment guidelines. As the understanding of POTS evolves, incorporating ivabradine into treatment guidelines could expand therapeutic options and improve patient outcomes, particularly in refractory cases.