OBJECTIVE: To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT). METHODS: Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up. RESULTS: All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up. CONCLUSION Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.
Child ; Humans ; Mutation ; Propranolol ; Ryanodine Receptor Calcium Release Channel/genetics* ; Syncope ; Tachycardia, Ventricular/diagnosis* ; United States

Humans ; Diagnosis, Differential ; Long QT Syndrome/genetics* ; Syncope/diagnosis* ; Epilepsy/diagnosis* ; Electrocardiography

Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1∶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ² test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.
Humans ; Child ; Adolescent ; Syncope, Vasovagal/etiology* ; Case-Control Studies ; Syncope ; Risk Factors

Objective: To analyze the clinical characteristics, diagnosis and treatment of anomalous aortic origin of a coronary artery (AAOCA) in children. Methods: There were 17 children diagnosed with AAOCA from January 2013 to January 2022 in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine.Their clinical manifestations, laboratory and imaging data, treatment and prognosis were retrospectively analyzed. Results: These 17 children included 14 males and 3 females, with the age of (8.7±3.5) years. There were 4 anomalous left coronary artery (ALCA) and 13 anomalous right coronary artery (ARCA). Seven children presented with chest pain or chest pain after exercise, three patients presented with cardiac syncope, one complained chest tightness and weakness, and the other six patients had no specific symptoms. Cardiac syncope and chest tightness occurred in patients with ALCA. Fourteen children had the dangerous anatomical basis of myocardial ischemia caused by coronary artery compression or stenosis on imaging. Seven children had coronary artery repair, of whom two were ALCA and five were ARCA. One patient had received heart transplantation because of heart failure. The incidence of adverse cardiovascular events and poor prognosis in ALCA group was higher than that in ARCA group (4/4 vs. 0/13, P<0.05). They were followed up in the outpatient department regularly for 6 (6, 12) months; except for the one who lost visit, the rest of the patients had a good prognosis. Conclusions: Cardiogenic syncope or cardiac insufficiency usually occurs in ALCA, and adverse cardiovascular events and poor prognosis are more common in ALCA than in ARCA. Early surgical treatment should be considered for children with ALCA and ARCA accompanied by myocardial ischemia.
Female ; Male ; Humans ; Child ; Child, Preschool ; Retrospective Studies ; China ; Coronary Artery Disease ; Myocardial Ischemia ; Heart Failure ; Chest Pain ; Syncope

Electrocardiography ; Female ; Humans ; Syncope/etiology* ; Torsades de Pointes/etiology*

Andersen Syndrome/genetics* ; Humans ; Syncope ; Tachycardia, Ventricular

Objective: To investigate the predictive value of blood cell parameters in children with vasovagal syncope (VVS). Methods: In this case-control study, the VVS group included 111 patients with unexplained syncope or prodromata who were diagnosed with VVS by head-up tilt test in the Second Xiangya Hospital, Central South University from January 2018 to October 2020, and 111 healthy children were enrolled as control. The differences in blood cell parameters between the 2 groups were compared by t test and Mann-Whitney U test. Multivariate binary Logistic regression was used to analyze the independent correlation factors of VVS, and receiver operating characteristic (ROC) curve to explore the predictive value of blood cell parameters for diagnosing VVS. Results: Sex composition ratios were consistent in the 2 groups (51 males vs. 60 females), while the age of the VVS group was higher than that of the control group (11.0 (8.0, 12.5) vs. 8.0 (7.0, 11.0) years, Z=4.39, P<0.001). Compared with the control group, VVS group had lower level of white blood cell (WBC) (6.0 (5.3, 7.1)×10⁹ vs. 8.6 (6.7, 10.1)×10⁹/L, Z=-7.96, P<0.001), lymphocyte (LY) (2.3 (1.9, 2.7)×10⁹ vs. 4.0 (2.8, 6.3)×10⁹/L, Z=-8.49, P<0.001), lymphocyte ratio (0.39 (0.33, 0.44) vs. 0.52 (0.37, 0.69), Z=-5.59, P<0.001), monocyte (0.3 (0.3, 0.4)×10⁹ vs. 0.4 (0.3, 0.6)×10⁹/L, Z=-6.19, P<0.001), eosinophil (0.1 (0.1, 0.2)×10⁹ vs. 0.2 (0.2, 0.4)×10⁹/L, Z=-5.75, P<0.001), mean corpuscular-hemoglobin concentration (MCHC) ((328±12) vs. (333±11) g/L, t=-3.27, P<0.001) and blood platelet (263 (235, 313)×10⁹ vs. 341 (295, 409)×10⁹/L, Z=-2.69, P<0.001), but higher neutrophil ratio (0.53 (0.48, 0.58) vs. 0.37 (0.22, 0.54), Z=5.86, P<0.001), hematocrit (0.39±0.04 vs. 0.37±0.04, t=2.75, P=0.006), mean corpuscular volume (MCV) (85 (82, 88) vs. 81 (78, 84) fl, Z=5.56, P<0.001), mean corpuscular hemoglobin (28 (27, 29) vs. 27 (26, 28) pg, Z=3.39, P=0.001), red cell distribution width (39 (37, 41) vs. 37 (36, 40) fl, Z=4.02, P<0.001) and mean platelet volume (11 (10, 11) vs. 10 (9, 11) fl, Z=2.81, P=0.005) levels. After adjusting for confounding factors such as sex and age, LY (OR=0.42, 95%CI 0.29-0.62, P<0.001), WBC (OR=0.75, 95%CI 0.59-0.95, P=0.015), MCHC (OR=0.94, 95%CI 0.91-0.97, P<0.001) were independent negative correlation factors of VVS, while MCV (OR=1.08, 95%CI 1.01-1.15, P=0.021) was independent positive correlation factor. ROC curve showed that the combination of LY, WBC, MCV and MCHC had acceptable predictive value for the diagnosis of VVS, with area under curve of 0.88, sensitivity of 0.80, specificity of 0.83, and Youden index of 0.63. Conclusions: Compared with healthy children, the blood cell parameters usually change in those with VVS. Combination of LY, WBC, MCHC and MCV can facilitate the diagnosis of VVS in children with unexplained syncope or prodromata.
Case-Control Studies ; Child ; Female ; Humans ; Lymphocytes ; Male ; Syncope ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

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. CONCLUSION 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.
Child ; Electrolytes ; Female ; Humans ; Male ; Metoprolol ; Midodrine ; Orthostatic Intolerance/therapy* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Salts ; Sitting Position ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Aneurysm, Dissecting/complications* ; Coronary Artery Disease/complications* ; Dyspnea/complications* ; Humans ; Syncope/etiology*

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 (SBP_CV), coefficient of variation of diastolic pressure (DBP_CV) and coefficient of variation of heart rate (HR_CV) 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 HR_CV,SBP_CV and DBP_CV 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 SBP_CV 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 SBP_CV 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 DBP_CV 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 DBP_CV 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 HR_CV 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 HR_CV 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 SBP_CV and HR_CV 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. SBP_CV ≥ 4.4% or HR_CV ≥ 10.5% of supine-erect position could be an indication of HUTT.
Blood Pressure ; Child ; Heart Rate ; Humans ; Orthostatic Intolerance/diagnosis* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test