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Background: A subset of patients with postural tachycardia syndrome (POTS) are thought to have a primary hyperadrenergic cause. We assessed clinical biomarkers to identify those that would benefit from sympatholytic therapy., Methods: We measured sympathetic function (supine muscle sympathetic nerve activity, upright plasma norepinephrine, and blood pressure responses to the Valsalva maneuver) in 28 patients with POTS (phenotyping cohort) to identify clinical biomarkers that are associated with responsiveness to the central sympatholytic guanfacine in a separate uncontrolled treatment cohort of 38 patients that had received guanfacine clinically for suspected hyperadrenergic POTS (HyperPOTS)., Results: In the phenotyping cohort, an increase in diastolic blood pressure (DBP) >17 mm Hg during late phase 2 of the Valsalva maneuver identified patients with the highest quartile of resting muscle sympathetic nerve activity (HyperPOTS) with 71% sensitivity and 85% specificity. In the treatment cohort, patients with HyperPOTS, identified by this clinical biomarker, more often reported clinical improvement (85% versus 44% in nonhyperadrenergic; P =0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: -1.9±0.9 versus 0.1±0.5; P =0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: -12.9±2.7 versus -2.2±2.2; P =0.005) in response to guanfacine., Conclusions: These results are consistent with the concept that POTS is caused by a central sympathetic activation in a subset of patients, which can be identified clinically by an exaggerated DBP increase during phase 2 of the Valsalva maneuver and improved by central sympatholytic therapy. These results support further clinical trials to determine the safety and efficacy of guanfacine in patients with POTS enriched for the presence of this clinical biomarker., Competing Interests: I. Biaggioni has received consultant fees and research support from Lundbeck and Theravance Biopharma Inc for the development of therapies for orthostatic hypotension. I. Biaggioni, L.E. Okamoto, J.K. Shirey-Rice, and J.M. Pulley have submitted a patent application for the use of guanfacine for the treatment of CFS. The other authors report no conflicts.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CB V ) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO 2 (ETCO 2 ; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CB V compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CB V reduction, we administered supplemental CO 2 , phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO 2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CB V . NEW & NOTEWORTHY We evaluated cognitive function before and after CO 2 , acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO 2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO 2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In this article we discuss the association of postural orthostatic tachycardia syndrome (POTS) with coronavirus-19 (COVID-19), ivabradine's unique mechanism of action, and its use in POTS patients. We highlight the pathophysiology and common etiologies of POTS, including preceding viral infections, vaccines, trauma, surgeries, and other stressors. COVID-19, a viral illness, has been associated with POTS through a variety of mechanisms that are not yet well understood. The initial management strategy for POTS is largely nonpharmacological, focusing on increasing venous return to the heart through physical therapy or other exercise activities. Ivabradine is a selective inhibitor of the funny sodium channels within the sinoatrial node. This unique mechanism of action allows for the reduction of heart rate without any effect on the heart's ionotropic activity. With an increase in the number of POTS cases, especially during the COVID pandemic, the importance of utilizing new medications and management strategies for POTS becomes imperative. Though ivabradine is currently only approved for the management of patients with coronary artery disease and heart failure by the Food and Drug Administration (FDA), it has also proven to be effective at reducing symptoms among patients with refractory POTS, and thus, should be considered for the management of patients who do not respond to initial treatment strategies., Competing Interests: There are no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The therapeutic effectiveness of the empirical and unselected use of oral rehydration salts (ORS) on postural tachycardia syndrome (POTS) is not satisfactory in children. Therefore, looking for suitable predictors of the therapeutic effects of ORS before treatment is extremely necessary to implement individualised treatment for paediatric patients with POTS., Methods: A retrospective case-control analysis of 130 patients (aged 5-18 years) who suffered from POTS with a 3-month treatment of ORS was conducted. A nomogram model was developed in the training set (n = 87) to predict the therapeutic response to ORS. Univariate analysis and logistic regression were applied to select the most useful predictors. ROC curves were applied to evaluate the discriminative performance of the nomogram model. The nomogram was then evaluated by calibration curves and the Hosmer-Lemeshow (H-L) test. The results were further validated using 1000 bootstrap resamples. External validation was performed in an independent validation set (n = 43)., Findings: Among the ten variables with significant differences between the responders and non-responders in univariate analysis, five variables were found to be independently associated factors for ORS therapeutic efficacy among POTS children in the further logistic regression, including mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean arterial pressure (MAP) at the first minute of the upright position, urine specific gravity (SG), and P-wave voltage peaking ratio (PWP). The nomogram model was established in the training set (AUC 0.926 [95% CI: 0.865-0.988], yielding a sensitivity of 87.8% and a specificity of 86.8%). The calibration curves showed good agreement between the prediction of the nomogram and actual observation in both the training and validation sets. The nomogram also effectively predicted the external validation set (sensitivity 82.1%, specificity 73.3%, and accuracy 79.1%)., Interpretation: We established a feasible and high-precision nomogram model to predict the efficacy of ORS, which would help implement individualised treatment for children with POTS., Funding: This study was supported by National High-Level Hospital Clinical Research Funding (Multi-centre Clinical Research Project of Peking University First Hospital) (2022CR59)., Competing Interests: Declaration of interests All authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood., Areas Covered: We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established., Expert Opinion: POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.

Objective: This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS)., Background: POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted., Methods: This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12 weeks, participants received eight infusions (0.4 gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2 weeks after final infusion., Results: A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups., Conclusions: This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Many patients with postural orthostatic tachycardia syndrome (POTS) are hypovolemic with plasma volume deficits of 10-30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in angiotensin II, pointing to potential adrenal dysfunction. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and cortisol following adrenocorticotropin hormone (ACTH) stimulation., Methods: While on a low Na + diet (∼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 μg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 μg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h., Results: Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8-61.8 ng/dL] vs. 46.1 ng/dL [36.7-84.9 ng/dL]; P = 1.000) or maximally (56.4 ng/dL [49.2-67.1 ng/dL] vs. 49.5 ng/dL [39.1-82.8 ng/dL]; P = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 μg/dL [36.1-47.7 μg/dL] vs. 39.3 μg/dL [35.4-46.6 μg/dL]; P = 0.724) or maximally (39.9 μg/dL [33.9-45.4 μg/dL] vs. 42.0 μg/dL [37.6-49.7 μg/dL]; P = 0.354)., Conclusions: ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to hormonal stimulation is intact in patients with POTS., Competing Interests: Declaration of competing interest CAS has served as a consultant for Lundbeck NA Ltd. and Theravance RSS. IB has served as a consultant for Lundbeck NA Ltd., Theravance RSS, Ammeal Pharmaceuticals, Regeneron, and Takeda Pharmaceutical. Patent holder of automated binder for treatment of Orthostatic Hypotension. RSS is a Cardiac Arrhythmia Network of Canada (CANet) Network Investigator. SRR is a consultant to Lundbeck LLC, Theravance Biopharma Inc., and Amneal Pharma related to neurogenic orthostatic hypotension; Consultant to Servier Affaires Medicales, Regeneron, argenx BV, and Antag Pharma related to postural orthostatic tachycardia syndrome. Honoraria from Spire Learning and Medscape for developing CME materials on neurogenic orthostatic hypotension. DMSB Chair for a Phase 2 study of an irritable bowel syndrome medication for Arena Pharmaceuticals with compensation. Past-President of the American Autonomic Society without financial compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There are differences in postural tachycardia syndrome (POTS) incidence and manifestations in children between the sexes. However, there is limited evidence on how the gender affects the prognosis of POTS in children. This study is aimed at exploring the differences between the sexes regarding the prognosis of children with POTS. A retrospective study was conducted on children (n = 53; aged 6-14 years) who were diagnosed with POTS. All the POTS patients were given health education and autonomic function training, their water and salt intake was increased (oral rehydration salt III, 250 mL, Bid), and they were administered oral metoprolol (1 mg/kg per day) for 3 months. The prognosis was defined by the head-up tilt test results after treatment. It was observed that male and female children exhibited different trends in POTS prognosis. Further, the sex showed a stable independent effect on prognostic in children with POTS. To elaborate, females had a 503% increased risk of poor prognosis compared to males. We hence hypothesize that there is an association between the sex and the POTS prognosis in children. Female patients have a significantly higher risk of poor prognosis compared to males. A slight increase in the dose of oral rehydration salt could help lower the risk of poor prognosis in children with POTS. A higher absorption of total metoprolol, lower local concentrations, and slower metabolic excretion are documented in research in female POTS patients during treatment. It is recommended that the optimal dose of metoprolol should be lowered in female children undergoing treatment, to limit the risk of poor prognosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The present work was designed to explore whether electrocardiogram (ECG) index-based models could predict the effectiveness of metoprolol therapy in pediatric patients with postural tachycardia syndrome (POTS)., Methods: This study consisted of a training set and an external validation set. Children and adolescents with POTS who were given metoprolol treatment were enrolled, and after follow-up, they were grouped into non-responders and responders depending on the efficacy of metoprolol. The difference in pre-treatment baseline ECG indicators was analyzed between the two groups in the training set. Binary logistic regression analysis was further conducted on the association between significantly different baseline variables and therapeutic efficacy. Nomogram models were established to predict therapeutic response to metoprolol. The receiver-operating characteristic curve (ROC), calibration, and internal validation were used to evaluate the prediction model. The predictive ability of the model was validated in the external validation set., Results: Of the 95 enrolled patients, 65 responded to metoprolol treatment, and 30 failed to respond. In the responders, the maximum value of the P wave after correction (Pcmax), P wave dispersion (Pd), Pd after correction (Pcd), QT interval dispersion (QTd), QTd after correction (QTcd), maximum T-peak-to-T-end interval (Tpemax), and T-peak-to-T-end interval dispersion (Tped) were prolonged (all P < 0.01), and the P wave amplitude was increased (P < 0.05) compared with those of the non-responders. In contrast, the minimum value of the P wave duration after correction (Pcmin), the minimum value of the QT interval after correction (QTcmin), and the minimum T-peak-to-T-end interval (Tpemin) in the responders were shorter (P < 0.01, < 0.01 and < 0.01, respectively) than those in the non-responders. The above indicators were screened based on the clinical significance and multicollinearity analysis to construct a binary logistic regression. As a result, pre-treatment Pcmax, QTcmin, and Tped were identified as significantly associated factors that could be combined to provide an accurate prediction of the therapeutic response to metoprolol among the study subjects, yielding good discrimination [area under curve (AUC) = 0.970, 95% confidence interval (CI) 0.942-0.998] with a predictive sensitivity of 93.8%, specificity of 90.0%, good calibration, and corrected C-index of 0.961. In addition, the calibration curve and standard curve had a good fit. The accuracy of internal validation with bootstrap repeated sampling was 0.902. In contrast, the kappa value was 0.769, indicating satisfactory agreement between the predictive model and the results from the actual observations. In the external validation set, the AUC for the prediction model was 0.895, and the sensitivity and specificity were 90.9% and 95.0%, respectively., Conclusions: A high-precision predictive model was successfully developed and externally validated. It had an excellent predictive value of the therapeutic effect of metoprolol on POTS among children and adolescents., (© 2023. The Author(s).)

Importance: Disorders of the autonomic nervous system are relatively common and have a significant impact on quality of life, offer very subtle diagnostic clues, and often mimic other disease processes, including certain psychiatric disorders. Pharmacologic treatment for psychiatric conditions in this group of patients can also be complicated by the pathophysiology of the various syndromes. Postural orthostatic tachycardia syndrome (POTS) is the final common pathway of a heterogenous group of underlying disorders that display similar characteristics., Observations: The current literature regarding the association between POTS and psychiatric conditions was reviewed. The literature showed an increased prevalence of mild/moderate depression and sleep disturbance in this population. Also, when psychiatric disorders occur in patients with POTS, clinicians may face challenges with regard to selecting appropriate psychopharmacologic interventions., Conclusions and Relevance: This review provides an evidence-based approach to treating common psychiatric conditions in those who suffer from POTS, with a particular emphasis on side effects that may worsen the associated symptoms. A list of the classes of psychopharmacologic treatment with a focus on adverse effects on heart rate and blood pressure is included, as is a case vignette of a patient with complex comorbid psychiatric conditions. It is of significant value to highlight the complexities associated with POTS; to raise awareness of the disorder, particularly in the context of psychiatric comorbidities; and to disseminate evidence-based information to aid clinicians in making informed medication choices with their patients., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Introduction: Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies., Areas Covered: In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic., Expert Opinion: Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A middle-aged woman was diagnosed with postural orthostatic tachycardia syndrome based on her clinical symptoms, elevated norepinephrine levels and positive tilt-table test. The patient was refractory to conventional treatment and improved only after she was treated with methylated B vitamins for her heterozygous catechol-O-methyltransferase Val158Met polymorphism., Competing Interests: Competing interests: PT: Amgen (consultant) Novo-Nordisk (consultant) Sanofi (consultant) Boehringer-Ingelheim (consultant) Epirium Bio (shareholder) Esperion therapeutics (consultant)., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS., Methods: This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics., Results: A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013)., Conclusions: Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Postural orthostatic tachycardia syndrome (POTS) is a common condition of orthostatic intolerance in response to changes in position. We report a case of a middle-aged woman presenting with a new onset of POTS likely due to chemotherapy for treatment of breast cancer. She was started on a trial of a beta blocker, which was effective in controlling her symptoms and heart rate. The objective of this report was to encourage clinicians to consider POTS as a differential diagnosis, while managing patients with symptoms of orthostatic intolerance., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A 22-year-old woman was referred with exertional dyspnoea and chest tightness 3 weeks following a diagnosis of COVID-19. Evaluation revealed a resting sinus tachycardia and criteria for postural orthostatic tachycardia syndrome were met. After non-pharmacological interventions failed to yield symptomatic improvement, ivabradine was commenced. This intervention was followed by a substantial improvement in the patient's exercise tolerance and energy levels and an objective reduction in supine and standing heart rate., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Postural tachycardia syndrome (POTS) is a form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. Recently, evidence has accumulated that in a subset of patients, the pathogenesis of dysautonomia may be immune-mediated. The aim of the current report was to evaluate the use of intravenous immunoglobulin (IVIG) treatment in patients with progressive and/or refractory immune-mediated POTS., Methods: We retroactively assessed the effect and tolerance of monthly administered IVIG in six patients using autonomic function testing, standardized symptom questionnaires, and patients' symptom diaries both before and 6 months into IVIG treatment. Objective outcome measures included heart rate increase after 10 min of head-up tilt as well as duration and anhidrotic area in a thermoregulatory sweat test. Subjective outcome measures were patient reports and symptom ratings from the symptom questionnaire., Results: All patients responded to immunomodulatory treatment, regardless of disease duration. After 6 months of IVIG, symptom severity was reduced by nearly 40%. Autonomic function testing showed improved cardiovascular functioning by 50% and a reduction of anhidrotic areas by one third. Overall, tolerance of IVIG treatment was poor, but could be improved by a reduction in infusion rate, premedication with steroids, and additional intravenous hydration., Conclusions: Using subjective but also standardized objective measures, the case series describes promising effects of IVIG treatment in POTS patients with immune-mediated dysautonomia. By reducing the infusion rate, pretreatment with steroids, and intravenous hydration, tolerance could be improved, and no patient had to discontinue the treatment., (© 2021 European Academy of Neurology.)

Background: Postural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological treatments are limited., Objectives: This study investigated the effect of ivabradine (selective blocker of the I funny channel in the sinoatrial node) on heart rate, quality of life (QOL), and plasma norepinephrine (NE) levels in patients with hyperadrenergic POTS defined by plasma NE >600 pg/ml and abnormal tilt table test., Methods: In total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month., Results: The average age was 33.9 ± 11.7 years, 95.5% were women (n = 21), and 86.4% were White (n = 23). There was a significant reduction in heart rate between placebo and ivabradine (p < 0.001). Patients reported significant improvements in QOL with RAND 36-Item Health Survey 1.0 for physical functioning (p = 0.008) and social functioning (p = 0.021). There was a strong trend in reduction of NE levels upon standing with ivabradine (p = 0.056). Patients did not experience any significant side-effects, such as bradycardia or hypotension, with ivabradine., Conclusion: Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype., Competing Interests: Funding Support and Author Disclosures A grant from Amgen was received to conduct this investigator-initiated clinical trial. No financial support was received in the writing of this paper. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the NIH (R01 DK118278-01 and R01 HL136407), the American Heart Association (SDG #15SDG2233005), and the Department of Homeland Security/FEMA (EMW-2016-FP-00788). Dr. Hsu has served as a consultant for Medtronic, Abbott, Boston Scientific, Biotronik, Biosense Webster, Zoll Medical, Pfizer, Bristol Myers Squibb, and Janssen Pharmaceuticals; has received research grants from Biosense Webster and Biotronik; and is a shareholder in Acutus Medical and Vektor Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Postural orthostatic tachycardia syndrome has been recognized for decades, but treatment is largely based on anecdotal experience and expert opinion. Pharmacologic treatment is inconsistent and unstandardized. We did a systematic review to identify controlled studies from which informed treatment decisions can be made., Method: Through a standard systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified all English-language studies of a medication treatment for postural orthostatic tachycardia syndrome that included a comparison or control group and followed outcomes for at least 1 week of treatment., Results: A total of 626 studies were identified by the search criteria, and 8, involving a total of 499 patients, met the criteria. No studies were adequately similar to allow for meta-analysis. Of the identified 8 studies, 2 were randomized controlled trials and 4 had been subjected to peer review. In individual studies, there was some favorable effect with fludrocortisone, beta blockers, midodrine, and selective serotonin reuptake inhibitors., Conclusion: There is a paucity of high-quality data about effectiveness of medication in the treatment of postural orthostatic tachycardia syndrome. Nonetheless, 2 randomized trials and 6 other reports show some favorable effects of medication.

Objective: To evaluate the ability of heart rate (HR) and HR difference during head-up tilt test (HUTT) and to predict clinical improvement related to metoprolol treatment in children and adolescents with postural tachycardia syndrome (POTS)., Study Design: This was a retrospective cohort study. A total of 53 subjects (27 male, aged 6-12 years old, mean age 11.79 ± 1.50 years old) with POTS treated with metoprolol were involved from July 2012 to September 2019. In total, 52 subjects who underwent health examination during the same period were matched as the control group. Subjects in both groups underwent HUTT. The HR distance between 5 minutes and 0 minutes (HR difference 5) and between 10 minutes and 0 minutes (HR difference 10) during HUTT was calculated., Results: The POTS group was significantly greater than the control group in HR 5, HR 10, HR difference 5, and HR difference 10 (P < .01). There was no statistical difference in HR 0 between the 2 groups (P > .05). In total, 53 subjects with POTS were followed up for 96.0 (IQR, 40.5, 134.5) days during treatment with metoprolol. HUTT results demonstrated that 58.49% of subjects with POTS had a response and symptom scores were reduced after intervention. HR and HR difference were useful in predicting the efficacy of metoprolol on POTS. When HR 5, HR 10, HR difference 5, and HR difference 10, respectively, were ≥110, 112, 34, and 37 beats/min, the sensitivity and specificity were 82.50% and 69.23%, 84.62% and 69.70%, 85.29% and 89.47%, and 97.56% and 64.86%, respectively., Conclusions: HR and HR difference are helpful to predict the efficacy of metoprolol on POTS in children and adolescents., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Postural orthostatic tachycardia syndrome (POTS) is estimated to impact millions of people each year. However, there is no established gold standard for its treatment. Bupropion is a norepinephrine and a dopamine reuptake inhibitor and has been implicated as a potential treatment for POTS. We performed a non-randomized retrospective chart review on 47 patients with POTS with statistical analysis evaluating for significant findings including reduced orthostasis and improvement of symptoms with the use of bupropion. Bupropion was not associated with a statistically significant improvement in orthostatic vitals but there was an overall reduction in reported syncope. While the use of bupropion does not show a statistically significant impact on orthostatic vitals in patients with POTS, it did show a degree of improvement in syncope and as such might be useful in patients with syncope-predominant POTS., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ivabradine is a unique medication that reduces the intrinsic heart rate by specifically blocking the inward funny current that controls the pacemaker activity of the sinus node. We conducted a retrospective cohort study to assess the efficacy of ivabradine in children suffering from postural orthostatic tachycardia syndrome., Methods: A chart review was conducted of patients less than 18 years of age who were diagnosed with postural orthostatic tachycardia syndrome who had received ivabradine as treatment from January 2015 to February 2019 at our institution. Twenty-seven patients (25 females, 92.5%) were identified for the study. The outcomes which were assessed included a change in the severity and frequency of symptoms, heart rate, and blood pressure before and after starting ivabradine., Results: There was an improvement in the symptoms of 18 (67%) out of 27 patients. The most notable symptom affected was syncope/presyncope with a reduction in 90%, followed by lightheadedness (85%) and fatigue (81%). The vital signs of the patients showed an overall significant lowering of the heart rate during sitting (89.7 ± 17.9 versus 73.2 ± 12.1; p-value <0.05) and standing (100.5 ± 18.1 versus 80.9 ± 10.1; p-value <0.05) without a significant change in the blood pressure. Two patients had visual disturbances (luminous phenomena). Severe bradycardia and excessive flushing were seen in two patients, respectively. Another one patient reported joint pain and fatigue., Conclusion: This study indicates that 67% of children treated with ivabradine report an improvement in symptoms.

Dysautonomia and headache are 2 common diagnoses within pediatric neurology; in the case of dysautonomia, a lack of consideration may lead to misdiagnosis. Despite being common conditions, there is a lot to learn about each individually as well as collectively. Many of the symptoms between headache and dysautonomia patients overlap making the diagnosis difficult. Migraine patients often exhibit symptoms of dysautonomia, namely postural orthostatic tachycardia syndrome (POTS); yet these symptoms are overlooked or lumped in as a part of their migraine diagnosis. The distinction or coexistence between dysautonomia and headache is identified through a thorough history, a full exam, and an open mind. This is crucial for the treatment and outcomes of these patients. Struggles arise when critical treatment differences are overlooked because dysautonomia is not considered. In this review, we will look at the epidemiology of dysautonomia and headache with focus on POTS and migraine. We will then compare the clinical features of both conditions as well as some hypothesized pathophysiology overlaps. We will conclude by summarizing the diagnostic approach and multitiered treatment options for POTS and migraine., (© 2019 American Headache Society.)

Syncope is a sudden loss and gain of consciousness. Traditionally, it is caused by the abnormalities of neurological, cardiac or vasovagal systems. We present a case of a 19-year-old woman presenting with recurrent syncopal episodes with no apparent cause. Examination and investigations were unremarkable for any aetiology except positive tilt tests for postural orthostatic tachycardia syndrome. The purpose of this report is to make physicians aware of the unique presentation of this rare aetiology with recurrent syncopal episodes and the novel management approach., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary headache syndromes and chronic pain syndromes are common in patients with postural tachycardia syndrome (POTS). There is overlap in potential mechanisms for migraine, chronic pain, and POTS symptomatology. Management of chronic pain and headaches in POTS requires a judicious use of pharmacotherapies that takes into account patient comorbidities and co-existing symptoms. Patient-centric, non-pharmacologic modalities include physical exercise, cognitive behavioral therapies, and treatment of sleep disorders., (Published by Elsevier B.V.)

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Postural orthostatic tachycardia syndrome encompasses multiple disabling symptoms that interfere with daily activities. Non-pharmacologic approaches can be insufficient and can require adjunctive medications to manage symptoms. Minimal data exist in the literature on medication outcomes in these patients. We reviewed our database for medication management outcomes.Materials and MethodsPatients aged 18 years and younger at initial diagnosis met the inclusion criteria. All prescribed patient medications were extracted from the electronic health record, excluding medications for unrelated symptoms or comorbid diseases. Medications were grouped by symptom class consistent with our programme utilisation protocol. Within symptom classification, therapy was deemed successful when a specific dose was prescribed at least five consecutive times without changes; this was confirmed by chart review. Individual medications and overall percentage of successful therapies within symptom classifications were assessed, with further analysis by gender. t-Test, χ2, and Mann-Whitney U-test were used to assess for differences in specific variables, as appropriate., Results: A total of 708 patients met the study criteria. The percentage of patients with effective therapy by symptom includes light-headedness (52.2%), headache (48.2%), nausea (39.1%), dysmotility (43.4%), pain (53.4%), and insomnia (42.8%). Insomnia therapy was better for females; all other therapies showed no gender difference. The median number of therapies prescribed per patient per symptom was 2 for light-headedness, headache, and insomnia, and 1 for nausea, dysmotility, and pain.DiscussionSymptoms associated with this disorder can be effectively managed with various medications. Further randomised studies are needed to better ascertain true efficacy compared with placebo.

Though a sizeable amount of data connects mast cell activity to the neurologic system, less is known about the true clinical implications of this relationship. Even less is understood about treatment strategies in those with both allergic and neurologic complaints. This is particularly true in postural orthostatic tachycardia syndrome (POTS), a common type of dysautonomia, where patients are burdened by symptoms of orthostatic cerebral hypoperfusion and several other comorbidities that are likely influenced by autonomic tone. Some patients describe characteristic allergic symptoms, in the absence of typical IgE mediated triggers, and also improvement with traditional mast cell directed medications. Further work is necessary to determine whether these anecdotal observations are valid. The answer to this question will likely be addressed as the mechanisms of POTS are better characterized, which may include a phenotype with distinct mast cell involvement., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Postural tachycardia syndrome (POTS) is a chronic condition characterized by symptoms of orthostatic intolerance. Pregnancy can cause different physiological changes in cardiovascular parameters, that could have greater impact on POTS patients. In this review, we discuss the management of POTS in the pregnant and obstetric settings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Postural orthostatic tachycardia syndrome (POTS) is a condition where the patient experiences tachycardia (a rise in heart rate of at least 30 beats per minute, 40 in people between the ages of 12 and 19) upon assuming the upright position, in the absence of orthostatic hypotension (a fall in systolic blood pressure of more than 20 mmHg). The majority of patients are young women. Symptoms are experienced frequently during standing, and include dizziness, fatigue, palpitations, tremulousness, blurred vision and sometimes syncope - although presyncope is more common. The diagnosis requires that symptoms have been present for at least six months and lack another medical explanation. The pathophysiology is believed to be multifactorial; peripheral sympathetic denervation, excessive sympathetic drive, hypovolemia and deconditioning have been reported in POTS. Patient education is fundamental in the management of POTS, including information regarding symptoms and exacerbating factors as well as methods for increasing arterial pressure. Exercise is believed to be effective. Several drugs can be used to relieve symptoms, although none of them are licensed for the treatment of POTS. We describe a case that illustrates that POTS can be debilitating, which requires awareness of the condition among clinicians.

Postural tachycardia syndrome (POTS) is a form of dysautonomia which presents with complex symptoms including orthostatic intolerance. Several medications are prescribed for POTS; however, the efficacy of sustained medical treatment has not been well-investigated. Here, we conducted a 2 × 2 factorial design, randomized, clinical trial of a 3-month medical treatment regimen in POTS patients. Patients were randomly allocated to 4 treatment groups (Group 1: propranolol; Group 2: bisoprolol; Group 3: propranolol + pyridostigmine; Group 4: bisoprolol + pyridostigmine). The orthostatic intolerance questionnaire (OIQ), Beck depression inventory-II (BDI-II), and short-form health survey (SF-36) were conducted at baseline, 1 and 3 months after treatment. Seventy-seven patients who completed the 3-month follow-up were analyzed. In total, every clinical score improved significantly after medical treatment. The OIQ score was significantly lower than that at baseline (18.5 ± 6.7) after 1 month (12.5 ± 4.5, P < 0.01), which decreased further after 3 months (7.8 ± 5.7, P < 0.01). The OIQ score improvements were consistent across every treatment group. In the subgroup analysis of 59 patients who did not receive antidepressants, the BDI-II score significantly decreased after treatment, regardless of the regimen. Physical components of the SF-36 improved after 3 months in every group, while mental components improved only in Group 3. The amount of changes in each score was similar among groups throughout the comparisons. Sustained medical treatment is beneficial to POTS patients, not only for orthostatic intolerance symptoms but also for depression and diminished quality of life, even without prescriptions for antidepressants. The efficacy of each regimen in POTS patients was comparable., Trial Registration: NCT02171988.

Introduction: Postural orthostatic tachycardia syndrome (POTS) impacts millions of patients, but there is currently no gold standard treatment for this condition. Ivabradine is a novel heart rate (HR) lowering agent that acts on the sinoatrial node cells by selectively inhibiting the If-current., Objective: The objective of this systematic review is to evaluate the evidence for the efficacy and safety of ivabradine for the treatment of POTS., Methods: MEDLINE (from 1956 to August 2017) and EMBASE (from 1957 to August 2017) were queried with the following search term: "postural orthostatic tachycardia syndrome" OR "postural tachycardia syndrome" OR "chronic orthostatic intolerance" AND "ivabradine." Articles in English with clinical outcomes of human patient(s) treated with ivabradine for POTS were included., Results: The initial search identified 73 articles. After screening, 13 articles were included. Two prospective open-label trials, three retrospective cohort studies, and eight case reports evaluated the safety and efficacy of ivabradine in a total of 132 patients with postural tachycardia. Overall, ivabradine lowered HR and provided symptomatic relief of POTS without blood pressure lowering. Dizziness, nausea, headache, and fatigue were the most common side effects and often did not lead to discontinuation of treatment., Conclusion: Based on this small sample, ivabradine appears to be a reasonable option for patients with POTS who have failed or are unable to tolerate other treatment options, however, but a randomized controlled trial in this population is needed.

Abstract: Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy., (© 2018 American Academy of Sleep Medicine.)

Objective: Ivabradine is a selective and specific inhibitor of the I(f) current in the sinoatrial and atrioventricular nodes. It decreases heart rate and myocardial oxygen consumption at rest and during exercise. It is used in adults for management of heart failure and angina, but promising results have been obtained in postural orthostatic tachycardia syndrome (POTS). There is little experience of ivabradine in childhood, although it is used on a compassionate basis. Our aim was to review our experience of ivabradine in a retrospective evaluation of pediatric patients with POTS., Methods: We evaluated all patients younger than 18 years for whom ivabradine had been prescribed for this indication, from February 2008 to June 2014., Results: Twenty-two patients were identified (15 female). Median age was 14.5 years (11-17 years). The ivabradine dosage after up-titration was 0.1 mg/kg per dose twice daily. In 15 (68%) symptoms improved. Ivabradine was suspended in five, but only in one for worsening of symptoms. There was a reduction in heart rate on resting electrocardiogram (EKG) from a mean (standard deviation) of 82.5 (13.6) bpm to a mean of 71 (16.5) bpm (p = 0.007). No patient had increased duration of QTc (p = 0.44). One (4.5%) experienced phosphenes., Conclusions: From this initial experience, ivabradine is safe in patients younger than 18 years with POTS. We observed improvement of symptoms in 68% and phosphenes in less than 5%. Further studies are needed to assess the safety in a randomized control setting.

A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO). A dramatic and sustained response was documented. The utility of IVIg in autoimmune neuromuscular diseases has been published, but clinical experience with POTS is relatively unknown and has not been reported in MCAS. As a short-acting mu-opioid antagonist, LDN paradoxically increases endorphins which then bind to regulatory T cells which regulate T-lymphocyte and B-lymphocyte production and this reduces cytokine and antibody production. IVIg is emerging as a promising therapy for POTS. Diagnosis and treatment of SIBO in POTS is a new concept and appears to play an important role., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Ivabradine is a selective I f  channel blocker that reduces heart rate without affecting other cardiovascular functions. In case reports and case series, it was shown to improve symptoms in patients with postural tachycardia syndrome (POTS)., Methodology and Results: This retrospective study examined patients who were diagnosed with POTS and received ivabradine as part of their treatment. Forty-nine patients (47 females, 95.9%) received ivabradine. The average age was 35.1 ± 10.35 years. The most common symptoms were palpitations and lightheadedness and both improved significantly, 88.4% and 76.1% response rate, respectively. A total of 38 patients reported improvement in their symptoms. In addition, ivabradine resulted in an objective decrease in sitting and standing heart rate (78.1 ± 10.7 vs 72.5 ± 7.6, P-value: 0.01) and (107.4 ± 14.1 vs 95.1 ± 13.7, P-value: < 0.001), respectively, with no significant change in blood pressure. The most common reported side effect was luminous phenomena/visual brightness occurring in nine patients. However, none of the patients stopped ivabradine due to side effects., Conclusion: Our study shows that ivabradine is likely to be effective in treating patients with POTS. Nearly 78% of our cohort reported a significant improvement in symptoms with no major adverse effects reported. A future randomized, placebo-controlled trial is warranted., (© 2017 Wiley Periodicals, Inc.)

Background: The postural tachycardia syndrome (POTS) is a heterogeneous group of disorders that results in symptoms of orthostatic intolerance. Excess blood pooling has been observed to cause low effective circulating volume in the central vasculature. Consequently, acute volume loading with IV saline has emerged as a potential strategy for clinical intervention. We evaluated the impact of acute volume loading on both the signs and symptoms of patients suffering from POTS., Methods: Fifty-seven subjects screened from our population of POTS patients and assenting to participation were administered the two surveys by telephone. Subjects completed each survey twice, before, and after initiating IV hydration therapy. The Orthostatic Hypotension Questionnaire (OHQ) was used to assess change in clinical symptomatology, while the short form 36 health survey (SF-36) was employed to assess the impact of IV saline infusion on quality of life., Results: Fifty-seven patients were included in the analysis. The average number of medications trialed before referral for IV hydration was 3.6 ± 1.7 medications. Saline infusions occurred with mean frequency of 11.3 ± 8.5 days and at a mean volume of 1.5 ± 0.6 l per infusion. The mean change of the OHQ was 3.1 ± 0.3 (95% CI 2.6-3.7; P < 0.001), with significant improvement in all the composite scores. The mean change in the SF-36 form was 19.1 ± 2.7 (95% CI -24.6 to -13.6; P < 0.001)., Conclusions: Intermittent IV infusions of saline dramatically reduce symptoms and improve quality of life in patients suffering from POTS. Further work should explore its efficacy as a bridge study for patients of high symptomatic severity.

Background: Postural orthostatic tachycardia syndrome (POTS) is a constellation of signs and symptoms that occur when a patient is upright and relieved by recumbence. Currently, no drugs are labeled for the treatment for POTS. Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance., Study Question: To appraise the effect of Droxidopa in a clinical setting in patients with POTS refractory to other forms of treatment., Study Design: A retrospective study of patients with POTS at our Syncope and Autonomic Disorders Center. Three hundred fifty-two patients were screened, 54 of them were prescribed Droxidopa and found to be eligible to include in our study., Measures and Outcome: Symptoms of orthostatic intolerance, side effects of therapy and response to treatment. Statistical analyses were done using SPSS software. Thirty-seven patients were included in data analysis. Patients who failed to follow up, didn't obtain Droxidopa due to insurance and cost concerns, had hypertensive response to therapy or had allergic reaction were excluded from data analysis., Results: The most frequently reported symptom was dizziness in 91.9% of patients, followed by syncope and fatigue in 70.3% and 67.6% of patients, respectively. Symptoms of dizziness, syncope and fatigue were reported less after treatment; 75.7%, 51.4% and 40.5%, respectively. There was no statistically significant difference in standing or sitting blood pressure before and after treatment. Despite the improvement in some symptoms. Only 27% of patients reported improved quality of life after treatment. Of total, 40.5% of patients stopped the treatment either due to side effects or ineffectiveness., Conclusion: Droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS but has diminutive impact on quality of life and blood pressure. Further assessment in large clinical trials is needed to evaluate its efficacy.

Objective: Postural tachycardia syndrome (POTS) is one of the major causes of orthostatic intolerance in children. We systematically reviewed the pathogenesis and the progress of individualized treatment for POTS in children., Data Sources: The data analyzed in this review are mainly from articles included in PubMed and EMBASE., Study Selection: The original articles and critical reviews about POTS were selected for this review., Results: Studies have shown that POTS might be related to several factors including hypovolemia, high catecholamine status, abnormal local vascular tension, and decreased skeletal muscle pump activity. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. However, reports about the effectiveness of various treatments are diverse. By analyzing the patient's physiological indexes and biomarkers before the treatment, the efficacy of medication could be well predicted., Conclusions: The pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. Biomarker-directed individualized treatment is an important strategy for the management of POTS children.

Objective: To explore the predictive value of upright blood pressure change for long-term prognosis of children with postural tachycardia syndrome (POTS) treated with midodrine hydrochloride., Method: A total of 90 children (male 41, female 49) were enrolled in this study. Their mean age was (11.8±2.7) years. They were diagnosed as POTS in Peking University First Hospital from 2005 to 2011. According to the upright change of blood pressure at the first visit, they were divided into two groups, effective group (n=55) and ineffective group(n=35). The follow-up time was 53-130 months. The orthostatic intolerance symptom score and symptom free survival rate were compared between the two groups., Result: The change of systolic blood pressure and of diastolic blood pressure was lower in effective group than those in ineffective group (0(-6, 0) mmHg (1 mmHg=0.133 kPa) vs. 9(6, 11) mmHg, Z=-8.303, P<0.01; 0(0, 5) mmHg vs. 11(10, 16) mmHg, Z=-7.058, P<0.01). Two groups had no significant difference in symptom scores before treatment((4.8±0.9) points vs. (5.0±0.8) points, t=-0.53, P=0.595), while symptom scores were lower in effective group than that in ineffective group((1.3±0.9) points vs. (4.7±0.9) points, t=-15.60, P<0.01 ). The symptom free survival rate was higher in effective group than that in ineffective group (48/55(87.3%) vs. 23/35(65.7%), χ(2)=5.969, P<0.01)., Conclusion: The upright change of blood pressure has a good predictive value on the long-term survival of POTS children treated with midodrine hydrochloride.

Ivabradine is a newly approved medication which reduces the heart rate by antagonizing the If channel. We report a case of intentional overdose on ivabradine. A 26-year-old female presented after taking 250 mg ivabradine. On arrival, her vital signs and neurologic exam were unremarkable. Within 30 min, her heart rate decreased to 31 bpm, but she remained normotensive with no change in mentation. Her bradycardia resolved after treatment with atropine. She experienced two further bradycardic episodes responsive to atropine; the second episode was associated with hypotension, responsive to a fluid bolus. For the remainder of her hospitalization, she remained hemodynamically stable without further interventions. She was dispositioned to the psychiatry service approximately 36 h post-ingestion with a heart rate of 67 bpm. Laboratory analysis confirmed a serum ivabradine concentration of 525 ng/mL, greater than 50 times the mean level in therapeutic trials. Proposed treatments for ivabradine include activated charcoal, atropine, isoproterenol, and intravenous pacing. Further study is needed to identify ideal treatment modalities.

Objective: To explore the predictive value of baseline plasma midregional fragment of pro-adrenomedullin level (MR-proADM) on long-term survival of postural tachycardia syndrome (POTS) children treated with midodrine hydrochloride., Methods: Fifty-three children (male 26, mean age (14.5 ± 4.5) years old) with POTS were included in this study, and all of them were diagnosed as POTS in our department from December 2007 to January 2010. Fifty-three children with POTS were divided into two groups according to the baseline plasma content of MR-proADM. Group I consisted of 35 POTS children with plasma content of MR-proADM > 61.5 ng/L, and the group II consisted of 18 POTS children with plasma content of MR-proADM ≤ 61.5 ng/L. The mean follow-up time was (67 ± 7) months. The orthostatic intolerance symptom score and the symptom free survival were compared between the 2 groups., Results: At the 60 months follow-up, the symptom score of children in group I was significantly lower than that in group II (χ(2) = 4.985, P < 0.05). At 72 months follow up, the symptom score was similar between the 2 groups (χ(2) = 0.004, P > 0.05) while the symptom free survival of group I was significantly higher than that in group II (χ(2) = 4.566, P < 0.05)., Conclusion: The baseline plasma MR-proADM level is value in predicting the long-term survival of POTS children treated with midodrine hydrochloride.