Predicting Therapeutic Efficacy of Pharmacological Treatments in Children with Postural Orthostatic Tachycardia Syndrome: A Mini-Review.

Postural orthostatic tachycardia syndrome (POTS) is common in children, with an excessive increment in heart rate when moving from the supine to upright position. It has significant negative impacts on the daily life of pediatric patients. The pathogenesis of POTS includes peripheral vascular dysfunction, central hypovolemia, abnormal autonomic function, a high-adrenergic state, impaired skeletal-muscle pump function, the abnormal release of vasoactive factors, and autoimmune abnormalities. Therefore, the empirical use of pharmacological treatments has limited therapeutic efficacy due to the diversity of its mechanisms. A crucial aspect of managing POTS is the selection of appropriate treatment targeting the specific pathogenesis. This review summarizes the commonly used pharmacological interventions, with a focus on their predictive indicators for treatment response. Factors such as heart rate variability, plasma biomarkers, and cardiac-function parameters are discussed as potential predictors of therapeutic efficacy, enabling the implementation of individualized treatment to improve therapeutic effectiveness. This review consolidates the current knowledge on POTS, encompassing its clinical characteristics, epidemiological patterns, underlying pathogenic mechanisms, and predictive indicators for treatment response. Further research is warranted to enhance the understanding of POTS and facilitate the development of more effective therapeutic approaches for this challenging syndrome.

Spectrum of underlying diseases in syncope and treatment of neurally-mediated syncope in children and adolescents over the past 30 years: A single center study.

Background: Syncope is the primary cause of transient loss of consciousness, which causes severe physical and mental burdens to children and adolescents. Objective: The study was designed to analyze the spectrum of underlying diseases of syncope and treatment options for neurally-mediated syncope (NMS) in Chinese children and adolescents. Methods: Medical records including history, physical examination, blood biochemistry, standing test, head-up tilt (HUTT), sitting-up test, electroencephalogram (EEG), electrocardiogram (ECG), and echocardiography were retrospectively studied in children and adolescents admitted to the National Pediatric Syncope Center, Department of Pediatrics, Peking University First Hospital between 1992 and 2021. All the data were collected from the Beijing Kaihua Medical Management System (Kaihua, Beijing, China). Children who met the syncope diagnostic criteria were enrolled in the study. The spectrum of the underlying diseases of syncope in children and adolescents and the treatment options of NMS were analyzed. Results: A total of 1,947 children and adolescents with syncope were admitted, including 869 males (44.63%) and 1,078 females (55.37%) aged 1-18 years, with an average age of 11.1 ± 3.1 years. The number of children and adolescents with syncope displayed a gradually increasing trend between 1992 and 2021 except after 2020. NMS proportion increased, and the proportion of unexplained syncope decreased (χ2 = 128.839, P < 0.01). The treatment options of NMS mainly included autonomic nervous function exercise (549, 34.46%), oral rehydration salt (ORS; 445, 27.94%), metoprolol (219, 13.75%), midodrine (120, 7.53%), ORS plus metoprolol (139, 8.73%), ORS plus midodrine (120, 7.53%), and pacemakers (1, 0.06%). Patients with vasovagal syncope (VVS) coexisting with postural orthostatic tachycardia syndrome (POTS) were more likely to take pharmacological treatments than those with VVS or POTS only (χ2 = 41.696, P < 0.01). Conclusion: The number of children with syncope displayed an increasing trend before 2020, and the proportion of unexplained syncope decreased. Autonomic nervous function exercise was the most common treatment for children and adolescents with NMS. Children with VVS coexisting with POTS were more likely to receive pharmacological treatments than those with either.

Baroreflex sensitivity predicts therapeutic effects of metoprolol on pediatric postural orthostatic tachycardia syndrome.

Objective: To determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children. Methods: In this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2-3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve. Results: The age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders (P > 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders (P < 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders (P < 0.01, P = 0.022, P < 0.01, P = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), P = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840-0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS. Conclusion: The baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized ß-adrenoceptor blocker use in pediatric patients suffering from POTS.

Clinical Efficacy of Empirical Therapy in Children with Vasovagal Syncope.

(1) Background: This case-control study was designed to assess the efficacy of empiric treatment for vasovagal syncope in children; (2) Methods: We retrospectively enrolled 181 children with vasovagal syncope from the Department of Pediatrics of Peking University First Hospital. The participants were categorized into four groups, based on the empiric treatment received: conventional treatment, including health education and orthostatic training; conventional treatment plus oral rehydration salts; conventional treatment plus metoprolol; conventional treatment plus midodrine hydrochloride. Patients were followed up to evaluate the syncopal or presyncopal recurrence. Kaplan-Meier curves were drawn to explore the syncopal or presyncopal recurrence in children, and the differences were compared among the groups using a log-rank test; (3) Results: Among the 181 children with vasovagal syncope, 11 were lost to follow-up. The median time of follow-up was 20 (8, 42) months. The Kaplan-Meier survival curve showed no significant difference in syncopal or presyncopal recurrence in children treated with different empiric options according to a log-rank test (χ2 = 1.328, p = 0.723); (4) Conclusions: The efficacy of unselected empiric therapy of vasovagal syncope in children was limited, and the individualized therapies merit further studies.

Plasma Fibroblast Growth Factor 23 as a Predictor for Fosinopril Therapeutic Efficacy in Pediatric Primary Hypertension.

Background Plasma fibroblast growth factor 23 (FGF23) has been reported to be a predictive biomarker for therapeutic effectiveness of angiotensin-converting enzyme inhibitors in heart failure. Higher plasma FGF23 levels have been shown in pediatric primary hypertension, but the predictive value of FGF23 for angiotensin-converting enzyme inhibitors' effectiveness in pediatric primary hypertension has not been documented. Methods and Results This is a prospective study. An exploratory study with 139 patients was first conducted to determine the cutoff value of FGF23 for the prediction of treatment responsiveness. After receiving fosinopril for 4 weeks, of all 139 patients, 91 responded, while 48 did not respond to the treatment, and the responders had a significantly higher baseline plasma FGF23 level than nonresponders (P<0.01). Multiple regression analysis revealed a significant impact of baseline plasma FGF23 levels on fosinopril responsiveness (P<0.05). The receiver operating characteristic curve analysis showed that the plasma FGF23 predicted the effectiveness of fosinopril treatment with an area under the curve of 0.784 (95% CI, 0.704-0.863) for a sensitivity and a specificity of 67.0% and 89.6%, respectively, for a cutoff value of 62.08 RU/mL. Subsequently, another group of 40 patients were recruited for validation. The blood pressure control rate in those (n=22) with baseline plasma FGF23 >62.08 RU/mL was significantly higher than that in children (n=18) with FGF23 ≤62.08 RU/mL (P<0.05). Conclusions Plasma FGF23 might be a valuable biomarker to guide fosinopril therapy for primary hypertension in children.