ObjectiveTo establish the quality standard of Liangditang benchmark samples. MethodUltra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF-MS） was used to qualitatively analyze the chemical composition of Liangditang on the basis of molecular and fragment ion peak information with cracking law. The mobile phase was methanol （A）-0.05% phosphate aqueous solution （B） for gradient elution （0-10 min， 5%-23.5%A； 10-20 min， 23.5%A； 20-58 min， 23.5%-63%A； 58-60 min， 63%-90%A）， the flow rate was 0.8 mL·min^-1， and the detection wavelength was 254 nm. Electrospray ionization was employed under positive ion mode， the detection range was m/z 100-1 700. Key quality attributes and sources were determined by comparing with single medicine and reference substances. Through mass transfer analysis of multiple batches from decoction pieces to benchmark samples， high performance liquid chromatography （HPLC） for determining the contents of index components and HPLC detection of characteristic maps were established. Through the determination of 15 batches of benchmark samples， the content range of the index components and the common peaks of the characteristic map were determined. Thin layer chromatography （TLC） was applied to the identification of 5 medicines in the formula. Moisture and dry extract yield of the benchmark samples were determined by drying method. ResultA total of 27 compounds were inferred from the benchmark samples of Liangditang， among which 9 compounds were confirmed by comparison with the control， including catalpol， harpagide， gallic acid， albiflorin， paeoniflorin， verbascoside， angoroside C， cinnamic acid and harpagoside. A method for determining the characteristic maps of the benchmark samples were established and 13 peaks were assigned， and the characteristic peaks were mainly derived from wine-processed products of Rehmanniae Radix， Scrophulariae Radix and wine-processed products of Paeoniae Radix Alba. The similarity between the characteristic map of 15 batches of benchmark samples and the control characteristic map was >0.9. Methods for the determination of paeoniflorin， harpagoside， L-hydroxyproline and glycine were established， and the contents of these four components in 15 batches of benchmark samples were within ±30% of the corresponding mean value， and the transfer rate of decoction pieces to the benchmark samples was stable and controllable. TLC was established to identify 5 prescription drugs （except Ejiao） with two kinds of test solutions， and the results showed that the method had good specificity. The average dry extract yield was 48.06%， and the average moisture was 5.58%， which were within the range of ±10% and ±30% of their mean values， respectively. ConclusionThe quality standard of Liangditang benchmark samples was as follows：the similarity between the benchmark samples and the control characteristic map is >0.9， the contents of paeoniflorin， harpagoside， L-hydroxyproline and glycine are 217-403， 24-46， 634-1 178， 1 253-2 328 mg per dose， the dry extract yield is 43.0%-53.0%， the moisture is 4.0%-7.0%， under the set detection conditions， the benchmark samples have corresponding characteristic spots by comparing with the control herbs of 5 medicines. This quality standard is stable and reliable， which fills the gap in the quality control of Liangditang， and can provide a reference for the establishment of the quality standard of Liangditang granules.

Objective:To explore the safety and efficacy of adenosine triphosphate (ATP) in terminating paro-xysmal supraventricular tachycardia (PSVT) in children and the correlation between its efficacy, age and dose.Methods:A retrospective analysis was performed on the clinical data, efficacy and adverse effects of intravenous ATP in 120 children who had received ATP emergency cardioversion among 1 488 children with PSVT hospitalized in the Department of Pediatric Cardiology, Heart Center, First Hospital of Tsinghua University from September 2014 to November 2019.There were 80 boys and 40 girls with the age of (3.50±3.66) years (25 d-15 years). As for the group comparison, the measurement data was subject to the independent samples t test and Mann- Whitney U test; the enumeration data was subject to χ2 test. Results:Among the 120 children with PSVT, there were 42 cases (35.0%) <1 year old, and 24 cases(20.0%) combined with congenital heart disease.There were 8.3% of them (10/120 cases) suffering from tachycardiomyopathy (TCM) secondary to PSVT, whose LVEF increased from (32.70±11.69)% to (40.50±11.63)% after successful control of PSVT ( t=-3.647, P=0.005). The complete termination of PSVT by intravenous ATP was achieved in 53 of 120 cases (44.2%). ATP was given at 0.3 mg/kg, 0.2 mg/kg and 0.1 mg/kg in dose, and the significant effective rate was 56.5%(13/23 cases), 36.4%(32/88 cases) and 0, respectively, which showed that there was a significant difference in the therapeutic effect between different dose groups ( χ2=10.058, P=0.007). There was a significant difference regarding the complete termination rate between children <1 year old and those ≥1 year old [31.0%(13/42 cases) vs.51.3%(40/78 cases), χ2=4.575, P=0.032]. For refractory PSVT, the intravenous ATP was performed based on the absence of cardioversion with continuous pumping of other antiarrhythmic drugs, which achieved a significantly complete termination rate of 55.6% (10/18 cases). The rate of ATP adverse reactions was 2.5%(3/120 cases), presented with sinus arrest in children >1 year old with the dose of 0.2-0.3 mg/kg. Conclusions:It was relatively safe and effective to terminate PSVT in children with ATP, which was related to dose and age.For refractory PSVT, ATP can be intravenously pushed on the basis of continuous pumping of other antiarrhythmic drugs, which can achieve a higher complete termination rate.

Objective:To identify the risk factors for cardiac events like recurrent syncope and fatal events in children with long QT syndrome (LQTS).Methods:A retrospective review involving 69 children with LQTS with the age of (7.6±4.2) years (43 male patients, 26 female patients) admitted in the Heart Center, Division of Pediatric Cardiology, First Hospital of Tsinghua University from August 2013 to March 2019 was conducted.Medical history, surface electrocardiogram, Doppler echocardiography and screening results of pathogenic genes of each patient were analyzed.Patients were divided into cardiac event group (32 cases) and non-cardiac event group (37 cases) according to the presence or absence of cardiac events like syncope or sudden death.Differences between 2 groups were compared using the independent sample Student′s t test and Chi- square test. Results:There were 32 cases among 69 children (46.4%) had recurrent syncope, involving 2 deaths, 14 cases among 69 children (20.3%) had a positive family history and 8 cases among 69 children (11.6%) had family history of sudden death.There were 52 cases among 69 children (75.4%) had arrhythmias.Among them, 32 patients (46.4%) with ventricular arrhythmia, including 11 cases (15.9%) with torsades de pointes (TdP). Ten LQTS-associated pathogenic or pathogenic pathologic mutations were found in 53 cases among 69 children (76.8%). Children with cardiac events had a younger mean age of onset [(4.7±4.1) years vs.(7.4±3.7) years, t=-2.856, P=0.006], a longer mean corrected QT (QTc) [(529±66) ms vs.(478±52) ms, t=3.537, P=0.001] and a higher incidence of TdP (34.4% vs.0%, P<0.001) compared with those who did not have cardiac events.Pathogenic mutations of KCNQ1 and KCNH2 were more frequent in children with cardiac events (62.5% vs.18.9%, χ2=14.178, P=0.001). Conclusions:Children with LQTS are prone to cardiac events.Children with a younger onset age, a longer QTc duration, malignant ventricular tachycardia and mutations of the KCNQ1 and KCNH2 genes are more frequently complicated by cardiac events.

Objective:To investigate clinical electrophysiological characteristics of idiopathic ventricular arrhythmias (VAs) and outcomes of radiofrequency catheter ablation (RFCA) in pediatric patients.Methods:A total of 328 consecutive pediatric patients with VAs and treated with RFCA in the First Hospital of Tsinghua University from January 2014 to December 2019 were recruited, involving 205 males and 123 females with the mean age of (7.8±3.9) years and the mean body weight of (32.8±17.7) kg.Their clinical electrophysiological characteristics, RFCA outcomes of different origins of VAs and complications were analyzed.Results:Among the 328 patients with the mean onset age of (5.4±4.1) years, 57.6% had frequent premature ventricular complex (PVC), 28.7% had paroxysmal ventricular tachycardia (VT) and 13.7% had incessant VT.A total of 38/328 cases (11.6%) VAs children were complicated with tachycardia-induced cardiomyopathy.Except for 13 cases of non-induced VAs, among 315 cases there were 152/328 cases (46.4%) originated from the ventricular outflow tract (including 46.1% of the origination of the right ventricular outflow tract septum, 27.6% of the origination of the left coronary cusp, 18.4% of the origination of the right coronary cusp, and 7.9% of the origination of the right ventricular outflow tract free wall), 55/328 cases (16.5%) originated from the tricuspid valve, 54/328 cases (17.4%) originated from the left posterior fascicle, 39/328 cases (11.9%) originated from the left posterior papillary muscle, 5/328 cases (1.5%) originated from multi-origin VAs, 3/328 cases (0.9%) originated from the left anterior fascicle, and 7/328 cases (2.1%) originated from other origins.Among 307/328 cases (93.6%) VAs patients receiving RFCA, 271/307 cases (88.3%) were instantly successful, 14/307 cases (4.6%) were effectively treated and 22/307 cases (7.2%) were invalid.During the follow-up time of 3 to 36 months, there were 42/271 cases (15.5%) recurrent cases.The mean radiation time and dose were (3.2±5.8) min, and (1.4±2.6) mGy, respectively.The mean dose-area product (DAP) was (384.2±42.6) mGy·cm 2.A total of 4/328 cases (1.2%) reported perioperative vascular complication.In 20 infant patients younger than 3 years, only 1 case was not induced during procedure of RFCA, and the remaining 19 cases were performed with RFCA, including 18/19 cases (94.7%) with an instant success and 4/18 (22.2%) recurrent cases during follow-up.There were 1/20 case (5.0%) had perioperative vascular complication caused by vascular puncture.No serious complications, such as myocardial perforation, cardiac tamponade and atrioventricular block were reported. Conclusions:The right ventricular outflow tract septum is the most common origin of the idiopathic VAs in pediatric patients.VAs originated from the ventricular outflow tract and tricuspid valve usually have an acceptable outcome following ablation.The recurrent rate is high following ablation in VAs cases originated from the left ventricular fascicle and posterior papillary muscle.RFCA is safe and effective for drug resistant or intolerant VAs in infants, but the surgical indications should be strictly mastered and operated by experienced pediatric electrophysiologists.The radiation dose of RFCA can be limited in a safe range under the guidance of the 3-dimensional mapping system.

Objective:To investigate the efficacy and feasibility of transthoracic implantation of permanent left atrial and left ventricular dual-chamber pacemaker for synchronous treatment of cardiac dysfunction due to idiopathic complete left bundle branch block (CLBBB) in children.Methods:The clinical data of five children with cardiac dysfunction due to idiopathic CLBBB and accepting implantation of permanent left atrial and left ventricular epicardial dual chamber pacemaker from January 2015 to July 2019 at the Pediatric Cardiologic Department of the First Hospital of Tsinghua University were analyzed retrospectively. The effects of pacemaker implantation on patients′ cardiac function and cardiac synchrony were evaluated by echocardiogram.Results:Among 5 patients, 2 were males and 3 females. At the time of pacemaker implantation, the age of these patients was 0.5-5.7 years, the left ventricle ejection fraction (LVEF) was 29%-46%, the left ventricle end stage of diastolic diameter was 30-53 mm and the mean Z score was 4.0-34.0. Pacemaker was successfully implanted for all the patients. After the implantation, medications that can suppress atrioventricular node conduction were used and sensed atrioventricular delay (SAV) parameters were modulated until patients′ QRS duration became shortest and the percentage of left ventricular pacing increased to and maintained at 97% to 100%. Patients′ QRS duration was 120-160 ms before implantation and 90-120 ms after implantation. Patients′ cardiac function began to improve 1 day to 1 month after implantation. Patients′ cardiac function normalized after a mean of 1-12 months. LVEF increased from 29%-46% to 55%-67%. During the follow-up, interventricular mechanical delay, septal-to-posterior wall motion delay, and left ventricular systolic dyssynchrony index decreased significantly: IVMD decreased from 31-62 ms to 26-50 ms; SPWMD decreased from 40-63 ms to 10-50 ms and Ts-SD decreased from 34.3-50.3 ms to 16.3-31.4 ms. The global longitudinal strain of left ventricle decreased from -7.7%--13.8% to -13.5%--20.3%.Conclusion:Cardiac dysfunction due to CLBBB in children can be treated with transthoracic implantation of permanent epicardial left atrial and left ventricular dual chamber pacemaker which can substitute three chamber pacemaker to achieve the effects of synchronous therapy that lead to reversion and normalization of cardiac function.

Objective:To investigate the clinical characteristics of focal atrial tachycardia (FAT) and the efficacy of radiofrequency catheter ablation (RFCA) in pediatric FAT.Methods:A total of 125 children with FAT who were treated with RFCA in the First Hospital of Tsinghua University from January 2010 to July 2018 were involved in the study. The clinical characteristics, origin of FAT, success rate of RFCA and recurrence rate and complications post RFCA were retrospectively analyzed, and the efficacy and X-ray radiation were compared between two-dimensional (2D) and 3D mapping system by t test or Chi-square analysis. Results:Among the 125 children, 57 were males and 68 females, age of (7.6±3.5) years old and body weight of (27.7±13.3) kg; and 62 (49.6%) had paroxysmal FAT, and 63 (50.4%) incessant FAT. Twenty-seven patients (21.6%) presented with tachycardia-induced cardiomyopathy (TIC), and 22 of whom (81.5%) were secondary to the incessant FATs. Most of the FATs originated from atrial auricle (46/125, 36.8%). Ablation was successful in 111 children (88.8%), and the recurrence rate was 25.2% (28/111). No complications were identified in the whole group. The efficacy and safety of 3D mapping system (87 cases) was better than that of the 2D mapping system (38 cases), according to the lower recurrence rate ((19.0% (15/79) vs. 40.6% (13/32), χ 2= 3.849, P=0.049), shorter X-ray exposure time ((4.9±2.3) vs. (12.5±5.7) min, t=7.942, P<0.01) and lower radiation doses ((5.3±3.3) vs. (10.9±3.7) mGy, t=8.038, P<0.01). Conclusions:FAT in children is mainly originated from atrial auricle, and incessant FAT is prone to progress to tachycardia-induced cardiomyopathy. RFCA is safe and effective for drug-resistant or drug-intolerant FAT in children, and 3D mapping system should be preferred.

Objective: To investigate the clinical characteristics and prognostic factors after catheter ablation of accessory pathway (AP)-induced dilated cardiomyopathy (DCM) in children. Methods: Data were collected and analyzed on 147 consecutive pediatric patients (81males and 66 females), who hospitalized in our pediatric heart center between January 2009 and August 2018 and received catheter ablation for ventricular pre-excitation (right AP). Thirty-one children were diagnosed as AP-induced DCM and 116 children with normal cardiac function served as control. Data including clinical characteristics, electrocardiogram (ECG), echocardiography, electrophysiological examination (EPS), successful ablation and follow up were analyzed. Results: The median age at first examination was 3.07 (0.09, 5.83) years. The pre-hospital misdiagnosis rate was 87.1% (27/31). The incidence of the AP-induced DCM was 21.1% (31/147) and the rate of right anterior free wall accessory pathway (AP) was the highest (50.0%, 10/20). AP-induced DCM was more common in right free wall Aps (41.9%, 13/31) and right anterior free wall (32.3%, 10/31). 48.4% (15/31) cases had no supraventricular tachycardia (SVT). EPS showed that 29% (9/31) of the AP did not have retrograde conduction. The median follow-up time after successful catheter ablation was 8 (2, 36) months of AP-induced DCM group, LVDd was significantly decreased ((41.6±12.8)mm vs. (45.6±13.9)mm, P<0.01) and LVEF ((56.2±11.8)% vs. (40.8±12.5)%, P<0.01) was significantly increased after ablation. Cox regression analysis showed that LVEF was the predictor of the duration of cardiac function recovery (HR=1.08, 95%CI 1.01-1.15, P=0.03). Conclusions Misdiagnosis rate is high for children with AP-induced DCM, leading to the delayed treatment. All of the AP-induced DCM occurred in right APs and right anterior free wall APs is the highest. Right free wall APs and right anterior free wall are most common in AP-induced DCM. Catheter ablation is a safe and effective treatment option for these patients. The lower the LVEF, the longer the cardiac function recovery.

Objective: To investigate the clinical features and results of treatment for right atrial appendage aneurysms complicated by atrial tachyarrhythmias in children. Methods: This retrospective study included three children with right atrial appendage aneurysm complicated by atrial tachyarrhythmias (aged 1.0 to 5.3 years, weight 10 to 17.1 kg) who were hospitalized at the Pediatric Cardiology Department (Heart Center) of the First Hospital of Tsinghua University (Beijing Huaxin Hospital) during the period from January 2016 through April 2018. The patients′ clinical features, the results of electrocardiogram (ECG) and echocardiography, the effects of therapeutic interventions (antiarrhythmics, radiofrequency ablation, and surgical resection of right atrial appendage aneurysm) and the results of pathological assessment were analyzed. Results: Three cases of right atrial appendage aneurysm were diagnosed at 36 weeks of gestational age, 1 month and 4 months after birth respectively. In two cases, ECG showed alternating episodes of atrial tachyarrhythmias including atrial tachycardia, atrial flutter, and atrial fibrillation, and echocardiography showed aneurysmal dilatation of right atrial appendage. These two cases underwent right atrial appendage aneurysm resection. In the remaining one case of atrial tachycardia, echocardiography did not visualize important lesions in the right atrium, thus the intracardiac electrophysiologic study and radiofrequency ablation were performed; and focal atrial tachycardia originating from the apex of right atrial appendage was mapped but failed to be ablated; consequently, the patient received the right atrial appendage resection, in which the right atrial appendage aneurysm was found. Preoperative multiple antiarrhythmics showed only modest or no efficacy for all the three cases. The atrial tachyarrhythmias disappeared in all the three cases after right atrial appendage aneurysm resection. Postoperative atrial tachycardias associated with new foci of impulse formation developed in two cases. These two patients reverted to normal sinus rhythm and remained in this rhythm by using antiarrhythmics. Pathological assessment showed cystic dilation of parts of atrial cavity, fibrosis of cyst wall, generalized fibrosis of atrial myocardium combined with myocardial atrophy and cystic dilation, as well as uneven myocardial thickness with generalized myocardial interstitial fibrosis. Conclusions For patients with congenital right atrial appendage aneurysm, atrial tachyarrhythmias might develop during fetal stage or early postpartum period. Reliance on echocardiography might often lead to the missed diagnosis. These patients with atrial tachyarrhythmias responded poorly to antiarrhythmics. Radiofrequency ablation might be associated with a high risk and limited efficacy. Surgical resection of right atrial appendage aneurysm showed satisfactory results and should be highly recommended.

Objective To assess the cLinicaL characteristics, pathogenic genes and therapeutic effects of congenitaL Long QT syndrome (LQTS) in chiLdren. Methods A retrospective anaLysis incLuded 58 LQTS chiLdren (37 boys, 21 girLs; age of diagnosis (8.0±4.1) years, range 0.1 to 16.0 years) at Division of Pediatric CardioLogy, First HospitaL of Tsinghua University from August 2013 to November 2017. Each patient was evaLuated with a detaiLed medicaL history, 12?Lead resting eLectrocardiogram, DoppLer echocardiography, and moLecuLar genetic anaLysis. ResuLts Forty?eight of the chiLdren (83%) had a deLay to diagnosis (0.7 (0.1, 2.0) years) and initiaLLy received a misdiagnosis. QT proLongation of unknown origin was found in 10 cases (17%), compLex arrhythmic conditions in 27 cases (47%), myocarditis in 3 cases (5%), syncope of unknown origin in 3 cases (5%), epiLepsy in 2 cases (3%), myocardiaL infarction in 1 case (2%), cardiomyopathy in 1 case (2%), and vasovagaL syncope in 1 case (2%). Nine chiLdren presented with the positive famiLy history of LQTS and three chiLdren had congenitaL nervous deafness. Twenty?one (36%) chiLdren presented with recurrent syncope, and 14 cases of whom had symptoms during physicaL activity and/or emotionaL stress. The common arrhythmias were ventricuLar arrhythmia (26 cases), sinus node dysfunction (18 cases), atrioventricuLar bLock (AVB) (12 cases), and atriaL arrhythmia (6 cases). LQTS?associated pathoLogic or possibLy pathoLogic mutations were found in 41 chiLdren (71%). Thirty?three chiLdren (57%) were treated with propranoLoL (22 cases), permanent pacemaker (PM) combined with propranoLoL (5 cases), PM (4 cases), and impLantabLe cardioverter defibriLLator (ICD) combined with propranoLoL (2 cases). Eighteen chiLdren (55%) were asymptomatic, thirteen chiLdren (39%) reported infrequent syncope, and one case (2%) died. ConcLusions LQTS in chiLdren is potentiaLLy maLignant and present as phenotypic diversity and compLex arrhythmias. LQTS?reLated pathogenic or possibLy pathogenic mutations are identified in most of the chiLdren. Beta?bLockers therapy is effective in reducing the risk of maLignant cardiac events. Some chiLdren with LQTS shouLd receive PM or ICD therapy.