Diagnosis and management of postural orthostatic tachycardia syndrome：A brief review

Postural orthostatic tachycardia syndrome （POTS） has been recognized since at least 1940.A review of the literature identifies differences in the definition for this condition and wide variations in treatment and outcomes.This syndrome appears to describe a group of conditions with differing pathophysiology,which requires treatment tailored to the true underlying disorder.Patients need to be fully evaluated to guide treatment.Further research is required to effectively classify the range of underlying pathophysioiogy that can produce this syndrome and to guide optimal management.

A predictive model of response to metoprolol in children and adolescents with postural tachycardia syndrome

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 dis-persion(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.

Pathophysiology and Individualized Management of Vasovagal Syncope and Postural Tachycardia Syndrome in Children and Adolescents:An Update

Vasovagal syncope(VVS) and postural tachycardia syndrome(POTS) are the main forms of orthostatic intolerance in pediatrics and both are underlying causes of neurally-mediated syncope.In recent years,increasing attention has been paid to the management of VVS and POTS in children and adolescents.A number of potential mechanisms are involved in their pathophysiology,but the leading cause of symptoms varies among patients.A few studies thus have focused on the individualized treatment of VVS or POTS based on selected hemodynamic parameters or biomarkers that can predict the therapeutic effect of certain therapies and improve their effectiveness.This review summarizes the latest developments in individualized treatment of VVS and POTS in children and indicates directions for further research in this field.

Clinical features and management of postural tachycardia syndrome in children： a single-center experience

Background The incidence of postural tachycardia syndrome （POTS） has been increasing in children and adolescents,while clinical characteristics of POTS in the pediatric population are not fully understood.Methods An observational study was performed in 150 pediatric patients aged between 5 and 18 years who underwent head-up tilt test （HUTT） with the diagnosis of POTS at Peking University First Hospital from March 2008 to August 2013.Demographic data,clinical presentation,autonomic parameters,laboratory findings,and treatments were recorded.Results POTS in children commonly occurred in the age of 7-14 years.Dizziness （84.00％） was the most common symptom,followed by weakness （72.00％） and orthostatic syncope （62.67％）.Positive family history of orthostatic intolerance （Ol） was found in 24.64％ of children with POTS.And 33.09％ of them had preceding infection history as precipitating events.Ten percent of them suffered from orthostatic hypertension.Hyperadrenergic status was documented in 51.28％ of 39 patients who were tested for the standing norepinephrine levels.More than half of POTS patients,with 24-hour urinary sodium level ＜124 mmol/24 hours,were suitable for treatment of salt supplementation.At least 25.74％ of POTS patients were of positive acetylcholine receptor （AChR） antibody.Low iron storage in children with POTS was relatively rare.Most patients responded well to treatments,43.51％ of patients recovered,while 7.63％ of them had relapse after symptoms disappeared.Conclusions POTS is a relatively common condition with complex pathophysiology and heterogeneous clinical manifestation.A comprehensive therapeutic regimen is recommended for the treatment.

A diagnosis-based health economic analysis of postural orthostatic tachycardia syndrome in Chinese children

Background Postural orthostatic tachycardia syndrome （POTS） is a common clinical problem in children and adolescents. The previous diagnostic approach to POTS of children and adolescents is based on a series of tests to exclude all other causes, which is time and medical resource consuming. Recently, a new diagnostic approach has been developed. The present study was designed to statistically analyze the results of clinical investigation items and the cost for the diagnosis of POTS in children patients, and evaluate cost changes in the diagnosis of POTS. Methods A total of 315 children patients were divided into two groups according to diagnosis period, including group I diagnosed in 2002-2006 （100 cases） and group II in 2007-2010 （215 cases） and the diagnostic item-based distribution of the cost was analyzed. The diagnostic costs were compared between two groups using SPSS17.0. Results The per-capita cost of diagnosis in group I was （621.95±2.1.10） Yuan, costs of diagnostic tests （head-up tilt test standing test, etc） accounted for 8.68% and the exclusive tests for 91.32%. The per-capita cost of diagnosis in group II was （542.69±2.3.14） Yuan, diagnostic tests accounted for 10.50% and exclusive tests for 89.50%. Comparison of the total cost of diagnostic tests between the two groups showed significant differences （P〈0.05）. Conclusion The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part.

Pathogenesis and Individualized Treatment for Postural Tachycardia Syndrome in Children

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.

Changes of atrial natriuretic peptide and antidiuretic hormone in children with postural tachycardia syndrome and orthostatic hypertension： a case control study

Background The abnormal blood volume regulation is one of the most important pathogenesis in postural tachycardia syndrome in children.This study was designed to investigate the plasma atrial natriuretic peptide and antidiuretic hormone levels in postural tachycardia syndrome children,and their associations with the changes in heart rate and blood pressure in head-up test.Methods Twenty-one postural tachycardia syndrome patients （（12±2） years） and 26 healthy children （（12±1） years） were included.According to blood pressure changes in head-up test,the postural tachycardia syndrome patients were divided into two subgroups：postural tachycardia syndrome with orthostatic hypertension and postural tachycardia syndrome without orthostatic hypertension.The plasma atrial natriuretic peptide and antidiuretic hormone levels were measured using enzyme-linked immunosorbent assay.Results The plasma atrial natriuretic peptide level in postural tachycardia syndrome patients was higher than the control （P=0.004）,whereas the difference in plasma antidiuretic hormone level between postural tachycardia syndrome and controls was not significant （P=0.222）.The plasma antidiuretic hormone level of patients suffering from postural tachycardia syndrome with orthostatic hypertension was much higher than that of children having postural tachycardia syndrome without orthostatic hypertension （P ＜0.05）.In postural tachycardia syndrome patients,the updght max heart rate was positively correlated with the plasma atrial natriuretic peptide level （r=0.490,P＜0.05） and the upright systolic blood pressure was positively correlated with the plasma antidiuretic hormone levels （r=0.472,P ＜0.05）.Conclusions There was a disturbance of plasma atrial natriuretic peptide and antidiuretic hormone in postural tachycardia syndrome children.

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy

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(DSS).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 DSS(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.

Increased Endogenous Sulfur Dioxide Involved in the Pathogenesis of Postural Tachycardia Syndrome in Children： A Case-Control Study

Background： The pathogenesis of postural tachycardia syndrome （POTS） remains unclear. This study aimed to explore the changes and significance of sulfur dioxide （SO2） in patients with POTS. Methods： The study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SO2was determined. Results： The plasma SO2was significantly higher in POTS children compared to healthy children （64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P 〈 0.05）. The symptom scores in POTS were positively correlated with plasma SO2levels （r = 0.398, P 〈 0.05）. In all the study participants, the maximum heart rate （HR） was positively correlated with plasma levels of SO2（r = 0.679, P 〈 0.01）. The change in systolic blood pressure from the supine to upright （ΔSBP） in POTS group was smaller than that in the control group （P 〈 0.05）. The ΔSBP was negatively correlated with baseline plasma SO2levels in all participants （r = ？0.28, P 〈 0.05）. In the control group, ΔSBP was positively correlated with the plasma levels of SO2（r = 0.487, P 〈 0.01）. The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 （95% confidence interval： 0.928–1.000）, and the cutoff value of plasma SO2level 〉38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS. Conclusions： Increased endogenous SO2levels might be involved in the pathogenesis of POTS.