UNASSIGNED: Orthostatic intolerance (OI) is the inability to tolerate orthostatic stress during any postural change. The etiology of OI varies, and methods to obtain a specific diagnosis and plan appropriate treatment are important. The tools available within the Chinese context to swiftly identify orthostatic intolerance syndrome (OIS) are currently limited.
UNASSIGNED: Patients with OI symptoms were included in this study and categorized into two groups based on the results of the supine-to-stand test. Those with abnormal test results were assigned to the OIS group, while those with normal test results were placed in the non-OIS group. We evaluated the internal consistency and predictive value of the Chinese Orthostatic Discriminant and Severity Scale (ODSS) by comparing patients\' scores with their physiological measurements collected during orthostatic stress tests and the results of other available questionnaires, including the orthostatic Symptom Questionnaire and Orthostatic Grading Scale (OGS).
UNASSIGNED: Patients with OIS scored significantly higher on all three questionnaires and showed significant differences in autonomic responses during orthostatic stress tests compared with non-OIS patients. Receiver operating characteristic curve analysis showed that the orthostatic score from the ODSS had moderate predictive value for the supine test (area under the curve [AUC] = 0.754). Further subgroup analysis revealed that the orthostatic score from the ODSS had uniquely high specificity and sensitivity for identifying patients with orthostatic hypotension with abnormal cerebral blood flow (OH-U, AUC = 0.919).
UNASSIGNED: We conclude that the Chinese version of the ODSS has sufficient reliability and validity to distinguish patients with OIS and could possibly be used as a diagnostic tool for OH-U patients. Thus, the Chinese ODSS offers a beneficial screening tool for quickly assessing whether patients have OIS that requires further clinical assessment.

BACKGROUND: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.
METHODS: Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis.
RESULTS: A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05).
CONCLUSIONS: The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.

UNASSIGNED: Orthostatic intolerance (OI) is usually mediated by the autonomic nerve and most often happens in the upright position. However, it can also occur in other positions and can be relieved by lying down while likely to have another attack after relief. In the current study, we aim to evaluate the predictive effect of catecholamines and electrolytes on the recurrence of OI in children.
UNASSIGNED: Children who were diagnosed with vasovagal syncope (VVS), postural tachycardia syndrome (POTS), and VVS combined with POTS were enrolled in this retrospective study and were followed up after 1-year physical treatment. Catecholamines in urine collected within 24 h, renin, angiotensin II, aldosterone in plasma, and electrolytes in both blood and urine collected in the morning were tested. A multivariate analysis and a receiver operating characteristic curve were used to validate the prediction effect.
UNASSIGNED: In the VVS cohort, the 24 h urine adrenaline (AD) and norepinephrine (NE) levels of the non-recurrence group were lower than the 24 h urine AD and NE levels of the recurrence group, with a significant difference of P < 0.05. A different content can also be witnessed in the POTS cohort that the urine of the non-recurrence group contained lower sodium and chlorine. As for the VVS + POTS cohort, the non-recurrence group has lower AD and NE levels and higher potassium and phosphorus levels in urine, the difference of which proved prominent as well.
UNASSIGNED: The study provides further evidence that AD, NE, and electrolytes in urine are promising factors that are closely related to the recurrence of OI in children. The integrated evaluation system merging AD and NE may have better predictive ability.

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options.
METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed.
RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ2= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS.
CONCLUSIONS: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

In children, vasovagal syncope and postural tachycardia syndrome constitute the major types of orthostatic intolerance. The clinical characteristics of postural tachycardia syndrome and vasovagal syncope are similar but their treatments differ. Therefore, their differential diagnosis is important to guide the correct treatment. Therapeutic methods vary in patients with the same diagnosis because of different pathomechanisms. Hence, in patients with vasovagal syncope or postural tachycardia syndrome, routine treatments have an unsatisfactory efficacy. However, biomarkers could increase the therapeutic efficacy significantly, allowing for an accurate and detailed assessment of patients and leading to improved therapeutic effects. In the present review, we aimed to summarize the current state of research into biomarkers for distinguishing the diagnosis of pediatric vasovagal syncope from that of postural tachycardia syndrome. We also discuss the biomarkers that predict treatment outcomes during personalized therapy for each subtype.

UNASSIGNED: To explore the role of the Poincaré plot derived from a 24-hour Holter recording in distinguishing vasovagal syncope (VVS) from postural tachycardia syndrome (POTS) in pediatric patients.
UNASSIGNED: Pediatric patients with VVS or POTS, hospitalized in Peking University First Hospital between January 2012 and December 2018, were included in a derivation study. The transverse axis (T), longitudinal axis (L), T/L ratio, product T × L, distance between the origin and the proximal end of the longitudinal axis (pro-D), and distance between the origin and distal end of the longitudinal axis (dis-D) of the Poincaré plot were compared between the VVS and POTS groups, and the differential diagnostic performance of the above-mentioned graphic parameters was evaluated using receiver operating characteristic curve analysis. A validation study was conducted in pediatric patients hospitalized between January 2019 and December 2020.
UNASSIGNED: In school-aged children, the T, L, T/L, T × L, and dis-D values of patients with VVS were greater than those of patients with POTS; in adolescents, the T, T/L, T × L, and pro-D values of patients with VVS were greater than those of patients with POTS. Using a T/L cut-off value of 0.3 to distinguish between the two diseases, the sensitivity and specificity were 91.0 and 90.5%, respectively, for the total participants; 91.6 and 88.9%, respectively, for the school-aged children; and 82.1 and 95.7%, respectively, for the adolescents. In the validation study, a T/L cut-off value of 0.3 yielded an accuracy, sensitivity, and specificity of 81.8, 87.2, and 77.6%, respectively, in the total participants; 76.5, 82.6, and 71.4%, respectively, in the school-aged children; and 89.2, 93.8, and 85.7%, respectively, in the adolescents, in distinguishing VVS from POTS validated by clinical diagnosis.
UNASSIGNED: The graphic parameters of the Poincaré plot are significantly different between VVS and POTS in pediatric patients, and the T/L of the Poincaré plot may be a useful measure to help differentiate VVS from POTS in children and adolescents.

OBJECTIVE: The study was designed to explore the role of baseline-corrected QT interval dispersion (QTcd) in predicting the effectiveness of metoprolol on pediatric postural tachycardia syndrome (POTS).
METHODS: There were two groups in the study, the discovery group and the validation group. The children with POTS in the discovery group were treated with oral metoprolol, with the completed necessary medical records, head-up tilt test (HUTT), blood chemistry, and 12-lead ECG before treatment at the pediatrics of Peking University First Hospital, China. According to whether the symptom score (SS) was reduced by more than 2 points after administration with oral metoprolol as compared with that before treatment, the children with POTS were separated into responders and non-responders. The demographic characteristics, hemodynamic indicators, and the QTcd of the two groups were compared, and the estimate of the baseline QTcd in predicting the treatment response to metoprolol was tested through a receiver operating characteristic (ROC) analysis. Other 24 children suffering from POTS who were, administrated with metoprolol at the pediatrics of Peking University First Hospital were included in the validation group. The sensitivity, specificity, and accuracy of the baseline QTcd in the prediction of the effectiveness of metoprolol on POTS were validated in children.
RESULTS: The pre-treatment baseline QTcd in responders treated with metoprolol was longer than that of the non-responders in the discovery group [(66.3 ± 20.3) ms vs. (45.7 ± 19.9) ms, p = 0.001]. The baseline QTcd was negatively correlated with SS after metoprolol treatment (r = -0.406, p = 0.003). The cut-off value of baseline QTcd for the prediction of the effectiveness of metoprolol on pediatric POTS was 47.9 ms, yielding a sensitivity of 78.9% and a specificity of 83.3%, respectively. The validation group showed that the sensitivity, specificity, and accuracy of the baseline QTcd ≥ 47.9 ms before treatment for estimating the effectiveness of metoprolol on POTS in children were 73.7, 80.0, and 75.0%, respectively.
CONCLUSIONS: Baseline QTcd is effective for predicting the effectiveness of metoprolol on pediatric POTS.

Objective: To investigate the clinical value of coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance(OI). Methods: This was a retrospective study. The medical records of 379 children with OI were collected, who were admitted to the Department of Pediatrics of Qilu Hospital of Shandong University from January 2015 to January 2020. Another 20 out-patient children without syncope or syncope aura were selected as control. According to the results of standing test and head-up tilt test (HUTT), all the patients with OI were divided into the following 4 groups: vasovagal syncope (VVS) group, postural tachycardia syndrome (POTS) group, POTS combined with VVS (POTS+VVS) group and HUTT negative group. Then, coefficient of variation of systolic pressure (SBPCV), coefficient of variation of diastolic pressure (DBPCV) and coefficient of variation of heart rate (HRCV) in standing test and HUTT were calculated. Kruskal-Wallis test was used for comparison among the five groups, and Dunnett\'s T3 method for comparison between two groups. Paired t test was used to compare the coefficient of variation between supine and erect position and tilt position in each group. The predictive values of HRCV,SBPCV and DBPCV for negative HUTT were evaluated by receiver operating characteristic (ROC) curve. Results: Among the 379 children, there were 79 in HUTT negative group, 208 in VVS group, 52 in POTS group, and 40 in POTS+VVS group. The SBPCV of supine-erect position of the control group, HUTT negative group, VVS group, POTS group, POTS+VVS group were (3.8±1.0)%, (5.3±2.2)%, (6.6±3.4)%, (5.9±3.6)%, (6.9±2.8)%, respectively. Similarly, the SBPCV of supine, erect and head-up tilt position were (4.5±0.8)%, (6.0±1.9)%, (7.1±2.6)%, (6.0±2.1)%, (7.3±2.5)%; the DBPCV of supine-erect position were (7.3±1.2)%, (9.1±3.7)%, (9.1±4.9)%, (9.1±4.8)%, (11.6±4.6)%; the DBPCV of supine, erect and tilt position were (7.4±1.1)%, (9.4±2.9)%, (10.1±3.8)%, (9.2±3.3)%, (11.0±4.7)%; the HRCV of supine-erect position were (7.6±2.6)%, (12.9±3.7)%, (16.2±4.3)%, (21.2±5.9)%, (24.9±5.3)%; and the HRCV of supine, erect and tilt position were (8.1±1.6)%, (10.1±2.7)%, (14.1±4.3)%, (15.6±3.7)%, (18.9±4.0)%, respectively. All the indexes showed significant differences among the five groups (χ2=21.91, 25.47, 19.82, 14.65, 104.52, 92.51, all P<0.05). ROC curve analysis showed that when the SBPCV and HRCV of supine-erect position reached 4.4% and 10.5%, the area under the curve of ROC were 0.713 and 0.877, the sensitivity of predicting negative HUTT were 58.2% and 78.5%, and the specificity were 80.0% and 95.0%, respectively. Conclusions: Coefficient of variation of heart rate and blood pressure may serve as potential diagnostic indexes in evaluating autonomic function of OI patients. SBPCV ≥ 4.4% or HRCV ≥ 10.5% of supine-erect position could be an indication of HUTT.
目的： 探讨心率及血压变异系数在可疑直立不耐受（OI）患儿快速识别中的临床应用价值。 方法： 回顾性研究。选取2015年1月至2020年1月山东大学齐鲁医院儿科诊治的379例因OI症状入院患儿为病例组；选取20名无晕厥及晕厥先兆症状的门诊健康查体儿童为无症状对照组。病例组根据直立试验及直立倾斜试验（HUTT）结果分为HUTT阴性组、血管迷走性晕厥（VVS）组、体位性心动过速综合征（POTS）组、POTS合并VVS组。分析所有入组儿童试验过程中的血压及心率数据，分别计算各组研究对象卧立位及卧立倾斜位收缩压变异系数（SBPCV）、舒张压变异系数（DBPCV）及心率变异系数（HRCV）。5组研究对象各项指标的组间比较采用Kruskal-Wallis检验，组间两两比较采用Dunnett′s T3法；5组内卧立位与卧立倾斜位变异系数比较采用配对样本t检验。通过受试者工作特征（ROC）曲线对卧立位心率及血压变异系数的预测价值进行评估。 结果： 379例患儿中，HUTT阴性组79例、VVS组208例、POTS组52例、POTS合并VVS组40例，无症状对照组20名。无症状对照组、HUTT阴性组、VVS组、POTS组、POTS合并VVS组患儿卧立位SBPCV分别为（3.8±1.0）%、（5.3±2.2）%、（6.6±3.4）%、（5.9±3.6）%、（6.9±2.8）%，卧立倾斜位SBPCV分别为（4.5±0.8）%、（6.0±1.9）%、（7.1±2.6）%、（6.0±2.1）%、（7.3±2.5）%，卧立位DBPCV分别为（7.3±1.2）%、（9.1±3.7）%、（9.1±4.9）%、（9.1±4.8）%、（11.6±4.6）%，卧立倾斜位DBPCV分别为（7.4±1.1）%、（9.4±2.9）%、（10.1±3.8）%、（9.2±3.3）%、（11.0±4.7）%，卧立位HRCV分别为（7.6±2.6）%、（12.9±3.7）%、（16.2±4.3）%、（21.2±5.9）%、（24.9±5.3）%，卧立倾斜位HRCV分别为（8.1±1.6）%、（10.1±2.7）%、（14.1±4.3）%、（15.6±3.7）%、（18.9±4.0）%，各项指标的5组间比较差异均有统计学意义（χ²=21.91、25.47、19.82、14.65、104.52、92.51，均P<0.05）；ROC曲线分析显示当卧立位SBPCV及HRCV分别为4.4%及10.5%时，曲线下面积分别为0.713及0.877，其对HUTT阴性组预测价值的灵敏度分别为58.2%及78.5%，特异度分别为80.0%及95.0%。 结论： 心率及血压的变异系数可作为OI患儿自主神经功能评价的一项参考指标；当卧立位SBPCV≥4.4%或HRCV≥10.5%时，建议行HUTT检查。.

Orthostatic intolerance (OI) refers to a series of symptoms that occur during upright standing, which can be relieved when returned to the supine position. OI is a common cause of syncope in children and adolescents. In recent years, more and more studies have been carried out to assess the prognosis of OI by using biomarkers, among which, flow-mediated vasodilation, left ventricular ejection fraction and fractional shortening, hemodynamic change during head-up tilt test, detection of 24-h urinary sodium excretion, body mass index, midregional pro-adrenomedullin, and erythrocytic H2S producing rate are relatively stable, inexpensive, and easy to obtain. With the help of biomarkers, individualized treatment can be carried out to improve the long-term prognosis of children and adolescents with OI. This article reviews the prognostic value of biomarkers in children and adolescents with OI.

Objectives: The head-up tilt test (HUTT) is a useful tool to assess autonomic function and to reproduce neurally mediated reflex. In this study, we evaluated the use of HUTT in pediatric patients aged 3-5 years with orthostatic intolerance. Materials and Methods: The medical history and HUTT records of 345 (180 males, aged from 3 to 5 years) cases of patients who complained of symptoms of orthostatic intolerance and who visited the Syncope Ward, Children\'s Medical Center, The Second Xiangya Hospital, Central South University from January 2003 to December 2019, were reviewed retrospectively. Results: Seventy-nine (22.9%) cases had positive responses to complete HUTT (basic HUTT and sublingual nitroglycerin HUTT), while 29 (8.4%) cases had positive responses if only basic HUTT was performed. Sublingual nitroglycerin provocation significantly increased the positive rate of the test (x 2= 27.565, P < 0.001). The most frequent hemodynamic response to HUTT was vasoinhibitory type vasovagal syncope (12.2%), Syncope (28.7%), and dizziness (22.6%) were the most common symptoms. Eight cases discontinued the test due to intolerable symptoms without severe adverse events occurring. Conclusions: HUTT was safe and well-tolerated and could be used to diagnose the hemodynamic type of orthostatic intolerance in children aged 3-5 years.