Xueying Li

Midregional Pro-Adrenomedullin as a Predictor for Therapeutic Response to Midodrine Hydrochloride in Children With Postural Orthostatic Tachycardia Syndrome

OBJECTIVES This study was designed to explore the predictive value of the midregional fragment of pro-adrenomedullin (MR-proADM) in assessing the therapeutic efficacy of midodrine hydrochloride for children with postural orthostatic tachycardia syndrome (POTS). BACKGROUND Midodrine hydrochloride is an important therapeutic option for children with POTS. However, there has not been any method to predict response to the drug. The MR-proADM is produced in equimolar amounts to adrenomedullin (ADM), and directly reflects levels of the rapidly degraded active peptide, ADM. METHODS Fifty-seven children with POTS were designated as the POTS group. Twenty healthy children served as the control group. The children in the POTS group received midodrine hydrochloride treatment. The plasma concentration of MR-proADM was measured, using a sandwich immunoluminometric assay. A receiver-operating characteristic curve was used to explore the predictive value of MR-proADM. RESULTS Plasma levels of MR-proADM were significantly higher in children with POTS (75.0 [62.5 to 96.0] pg/ml) than in the control group (58.5 [50.3 to 69.0] pg/ml). Plasma levels of MR-proADM in responders to midodrine hydrochloride was significantly higher than that of nonresponders (76.0 [66.0 to 91.0] pg/ml vs. 59.0 [54.0 to 65.5] pg/ml, p < 0.01]. A receiver-operating characteristic curve on the predictive value of MR-proADM showed that the area under the curve was 0.879 with a 95% confidence interval of 0.761 to 0.997. Using a cutoff value for MR-proADM of 61.5 pg/ml produced both high sensitivity (100%) and specificity (71.6%) in predicting the efficacy of midodrine hydrochloride therapy for treating POTS. CONCLUSIONS MR-proADM can help guide midodrine hydrochloride therapy in the management of POTS in children.

Plasma hydrogen sulfide in differential diagnosis between vasovagal syncope and postural orthostatic tachycardia syndrome in children.

OBJECTIVE To explore the predictive value of plasma hydrogen sulfide (H(2)S) in differentiating between vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children. STUDY DESIGN Patients were divided between the POTS group (n=60) and VVS group (n=17) by using either the head-up test or head-up tilt test. Twenty-eight healthy children were selected for the control group. Plasma concentrations of H(2)S were determined for children in all groups (POTS, VVS, and control). RESULTS Plasma levels of H(2)S were significantly higher in children with VVS (95.3±3.8 μmol/L) and POTS (100.9±2.1 μmol/L) than in children in the control group (82.6±6.5 μmol/L). Compared with the VVS group, the POTS group had plasma levels of H(2)S that were significantly increased. The receiver operating characteristic curve for the predictive value of H(2)S differentiation of VVS from POTS showed a H(2)S plasma level of 98 μmol/L as the cutoff value for high probability of distinction. Such a level produced both high sensitivity (90%) and specificity (80%) rates of correctly discriminating between patients with VVS and patients with POTS. CONCLUSION H(2)S plasma level has both high sensitivity and specificity rates to predict the probability of correctly differentiating between patients with VVS and patients with POTS.

Postural orthostatic tachycardia syndrome with increased erythrocytic hydrogen sulfide and response to midodrine hydrochloride.

OBJECTIVES To evaluate the use of erythrocytic hydrogen sulfide (H2S) in predicting the therapeutic efficacy of midodrine hydrochloride for children with postural orthostatic tachycardia syndrome (POTS). STUDY DESIGN Fifty-five children were included in this study, involving 28 children with POTS (POTS group) and 27 healthy children (control group). Children in the POTS group received midodrine hydrochloride treatment. Erythrocytic H2S production was measured; a receiver operating characteristic curve was used to assess if erythrocytic H2S could predict the therapeutic response to midodrine hydrochloride treatment. RESULTS H2S production from erythrocytes was significantly higher in the POTS group than in the control group (P < .01). H2S production was also significantly higher in responders to midodrine hydrochloride than in non-responders (P < .05). The change in symptom score and baseline erythrocytic H2S production had a positive linear relationship (P < .01). There was also a positive correlation with the change in heart rate (P < .05). The receiver operating characteristic curve showed an area under curve value of 0.813. Erythrocytic H2S production yielded a sensitivity of 78.9% and a specificity of 77.8% in predicting the efficacy of midodrine hydrochloride therapy for children with POTS. CONCLUSION Erythrocytic H2S could serve as a useful predictor of therapeutic response to midodrine hydrochloride in children with POTS.

α-Adrenoceptor agonists for the treatment of vasovagal syncope: a meta-analysis of worldwide published data

Aim:  The present study was aimed at evaluating present randomized controlled trials (RCTs) regarding the effect of α‐adrenoceptor agonists on vasovagal syncope (VVS).

Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.

POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP) in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS) in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive) sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4) vs. (25.1 ± 19.1) pg/ml, P <0.001]. Plasma CNP in responders to metoprolol was significantly higher than non-responders [(59.1 ± 33.5) vs. (34.8 ± 16.7) pg/ml, P = 0.037] before treatment. The ROC curve showed that area under the curve was 0.821 (95% CI 0.642–0.999). The cut-off value of plasma CNP > 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

Anatomic Distribution of Nerves and Microvascular Density in the Human Anterior Vaginal Wall: Prospective Study

Background The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot. Methods Biopsies were drawn from a 12 o’clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5–immunoreactive nerves and smooth muscle actin–immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. Results Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002). Conclusions Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction.

Risk Factors for Postural Tachycardia Syndrome in Children and Adolescents

Background Postural tachycardia syndrome (POTS) is prevalent in children and adolescents and has a great impact on health. But its risk factors have not been fully understood. This study aimed to explore possible risk factors for children and adolescents with POTS. Methods and Findings 600 children and adolescents (test group) aged 7–18 (11.9±3.0) years old, 259 males and 341 females, were recruited for identifying its risk factors. Another 197 subjects aged from 7 to 18 (11.3±2.3) years old were enrolled in the validation group. Heart rate (HR) and blood pressure (BP) were monitored during upright test. Risk factors were analyzed and sensitivity and specificity for predicting POTS were tested via receiver operating characteristic curve. Among 600 subjects, 41 were confirmed with POTS patients (6.8%) based on clinical manifestation and upright test. The results showed a significant difference in daily water intake, the daily sleeping hours, supine HR, HR increment and maximum HR during upright test between POTS and the unaffected children (P<0.05). Likelihood of POTS would increase by 1.583 times if supine HR was increased by 10 beats/min (95%CI 1.184 to 2.116, P<0.01), by 3.877 times if a childs water intake was less than 800 ml/day (95%CI 1.937 to 7.760, P<0.001), or by 5.905 times (95%CI 2.972 to 11.733, P<0.001) if sleeping hours were less than 8 hours/day. Supine HR, daily water intake and sleeping hours showed the capability of predicting POTS in children and adolescents with an AUC of 83.9% (95% CI: 78.6%–89.1%), sensitivity of 80.5% and specificity of 75%. Furthermore, in validation group, predictive sensitivity and specificity were 73.3% and 72.5%. Conclusion Faster supine HR, less water intake and shorter sleeping hours were identified as risk factors for POTS.

A clinical manifestation-based prediction of haemodynamic patterns of orthostatic intolerance in children: a multi-centre study.

OBJECTIVE At present, the haemodynamic diagnosis of orthostatic intolerance is based mainly on the head-up tilt table test, which is sometimes risky for patients. Thus, it is important to find objective and safe methods to differentiate haemodynamic patterns of orthostatic intolerance cases. METHODS In all, 629 children with orthostatic intolerance, either vasovagal syncope or postural orthostatic tachycardia syndrome, were included in the multi-centre clinical study. We analysed the association between the clinical manifestation and haemodynamic patterns of the patients. RESULTS Syncope after motion with a prodrome of chest distress or palpitations and the concomitant symptom(s) after a syncopal attack, with debilitation, dizziness or headache, were the most important variables in predicting the diagnosis of vasovagal syncope. The overall diagnostic accuracy was 71.5%. CONCLUSION Complaint of syncope after motion with prodromal chest distress or palpitation and the concomitant symptom after a syncopal attack, with subsequent debilitation, dizziness or headache, were the most important variables in the diagnosis of vasovagal syncope in children with orthostatic intolerance.

Modified Calgary score in differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope in children.

The present study was designed to analyse the usefulness of a modified Calgary score system during differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope through a large sample sized clinical investigation. The study included 213 children, including 101 boys and 112 girls, with cardiac syncope or postural orthostatic tachycardia syndrome-associated syncope in the age group of 2-19 years (mean 11.8 ± 2.9 years). A modified Calgary score was created, which was analysed to predict differential diagnoses between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope using a receiver operating characteristic curve. The median of modified Calgary scores for cardiac syncope was -5.0, which significantly differed from that of postural orthostatic tachycardia syndrome (0.0; p < 0.01). The sensitivity and specificity of a differentiation score of less than -2.5 was 96.3% and 72.7%, respectively. Owing to the fact that the modified Calgary score was an integer, when less than -3.0 the diagnosis could be considered as cardiac syncope. The modified Calgary score could be used to make an initial differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope in the clinic.

A cross-sectional study on upright heart rate and BP changing characteristics: basic data for establishing diagnosis of postural orthostatic tachycardia syndrome and orthostatic hypertension

Objective We aimed to determine upright heart rate and blood pressure (BP) changes to suggest diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) and orthostatic hypertension (OHT) in Chinese children. Methods In this cross-sectional study, 1449 children and adolescents aged 6–18 years were randomly recruited from two cities in China, Kaifeng in Henan province and Anguo in Hebei province. They were divided into two groups: 844 children aged 6–12 years (group I) and 605 adolescents aged 13–18 years (group II). Heart rate and BP were recorded during an active standing test. Results 95th percentile (P95) of δ heart rate from supine to upright was 38 bpm, with a maximum upright heart rate of 130 and 124 bpm in group I and group II, respectively. P95 of δ systolic blood pressure (SBP) increase was 18 mm Hg and P95 of upright SBP was 132 mm Hg in group I and 138 mm Hg in group II. P95 of δ diastolic blood pressure (DBP) increase was 24 mm Hg in group I and 21 mm Hg in group II, and P95 of upright DBP was 89 mm Hg in group I and 91 mm Hg in group II. Conclusions POTS is suggested when δ heart rate is ≥38 bpm (for easy memory, ≥40 bpm) from supine to upright, or maximum heart rate ≥130 bpm (children aged 6–12 years) and ≥125 bpm (adolescents aged 13–18 years), associated with orthostatic symptoms. OHT is suggested when δ SBP (increase) is ≥20 mm Hg, and/or δ DBP (increase) ≥25 mm Hg (in children aged 6–12 years) or ≥20 mm Hg (in adolescents aged 13–18 years) from supine to upright; or upright BP≥130/90 mm Hg (in children aged 6–12 years) or ≥140/90 mm Hg (in adolescents aged 13–18 years).