Search

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P

Inherited cardiovascular conditions are significant causes of sudden cardiac death in the young (SCDY), making their investigation using molecular autopsy and prevention a public health priority. However, the molecular autopsy data in Chinese population is lacking. The 5‐year result (2017–2021) of molecular autopsy services provided for victims of SCDY (age 1–40 years) was reviewed. The outcome of family cascade genetic screening and clinical evaluation was reviewed. A literature review of case series reporting results of molecular autopsy on SCDY in 2016–2023 was conducted. Among the 41 decedents, 11 were found to carry 13 sudden cardiac death (SCD)‐causative genetic variants. Likely pathogenic (LP) variants were identified in the DSP, TPM1, TTN, and SCN5A genes. Cascade genetic testing identified four family members with LP variants. One family member with familial TPM1 variant was found to have hypertrophic cardiomyopathy upon clinical evaluation. This study provided insight into the genetic profile of molecular autopsy in a Chinese cohort of SCDY. The detection of important SCD‐causative variants through molecular autopsy has facilitated family cascade screening by targeted genetic testing and clinical evaluation of at‐risk family members. A literature review of the current landscape of molecular autopsy in the investigation of SCDY was conducted. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome (BrS) is an inherited channelopathy characterized by right precordial ST-segment elevation. This study investigates the clinical and genetic characteristics of children with BrS in Hong Kong., Methods: A retrospective review was conducted at the only tertiary pediatric cardiology center in Hong Kong from 2002 to 2022, including all pediatric BrS patients under 18 years old. The diagnosis of BrS was established with a type 1 ECG pattern detected spontaneously or induced by flecainide, excluding secondary causes., Results: Eight probands of mean age 10 years old were identified. Male dominance was observed (6 boys vs. 2 girls). The mean follow-up duration was 4.6 years (Median 3.5 years). Patients had type 1 ECG pattern either spontaneously (n = 4) or provoked by flecainide (n = 4). Fever was present in seven patients at the initial presentation, and two patients experienced aborted cardiac arrest and one had symptomatic ventricular tachycardia. All symptomatic patients received implantable cardioverter-defibrillator placement. Five asymptomatic patients (62.5%) were diagnosed with BrS through ECG during febrile illness, and they remained asymptomatic following conservative management involving strict fever control and medication avoidance. Two patients with mixed phenotype (one with long QT syndrome and another with ectopic atrial tachycardia) required antiarrhythmics and one patient received transcatheter ablation for atrial tachycardia to achieve optimal arrhythmia control., Conclusion: Fever plays a significant role in unmasking BrS in children. Asymptomatic children with BrS managed conservatively have a favorable prognosis. Difficult arrhythmia control was found in patients with mixed phenotype., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: Precision medicine in paediatric cardiac channelopathy and cardiomyopathy has a rapid advancement over the past years. Compared to conventional gene panel and exome-based testing, whole genome sequencing (WGS) offers additional coverage at the promoter, intronic regions and the mitochondrial genome. However, the data on use of WGS to evaluate the genetic cause of these cardiovascular conditions in children and adolescents are limited., Methods: In a tertiary paediatric cardiology center, we recruited all patients diagnosed with cardiac channelopathy and cardiomyopathy between the ages of 0 and 18 years old, who had negative genetic findings with prior gene panel or exome-based testing. After genetic counselling, blood samples were collected from the subjects and both their parents for WGS analysis., Results: A total of 31 patients (11 cardiac channelopathy and 20 cardiomyopathy) were recruited. Four intronic splice-site variants were identified in three cardiomyopathy patients, which were not identified in previous whole exome sequencing. These included a pathogenic variant in TAFAZZIN:c.284+5G>A (Barth syndrome), a variant of unknown significance (VUS) in MYBPC3:c.1224-80G>A and 2 compound heterozygous LP variants in LZTR1 ( LZTR1:c.1943-256C>T and LZTR1:c1261-3C>G ) in a patient with clinical features of RASopathy. There was an additional diagnostic yield of 1.94% using WGS for identification of intronic variants, on top of conventional gene testing., Conclusion: WGS plays a role in identifying additional intronic splice-site variants in paediatric patients with isolated cardiomyopathy. With the demonstrated low extra yield of WGS albeit its ability to provide potential clinically important information, WGS should be considered in selected paediatric cases of cardiac channelopathy and cardiomyopathy in a cost-effective manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kwok, Kwong, Shi, Shih, Lee, Mak, Chui, Tsao and Chung.)

Background: Apple watch-derived electrocardiogram (awECG) may help identify prolongation of corrected QT (QTc) interval. This study aimed to determine its usefulness for assessment of prolongation of QTc interval in children and adolescents with long QT syndrome (LQTS)., Methods: Children and adolescents with and without LQTS were recruited for measurement of QTc intervals based on standard 12-lead (sECG) and awECG lead I, II and V5 tracings. Bland-Altman analysis of reproducibility, concordance assessment of T wave morphologies, and receiver operating characteristic (ROC) analysis of sensitivity and specificity of awECG-derived QTc interval for detecting QTc prolongation were performed., Results: Forty-nine patients, 19 with and 30 without LQTS, aged 3-22 years were studied. The intraclass correlation coefficient was 1.00 for both intra- and inter-observer variability in the measurement of QTc interval. The awECG- and sECG-derived QTc intervals correlated strongly in all three leads (r = 0.90-0.93, all p < 0.001). Concordance between awECG and sECG in assessing T wave morphologies was 84% (16/19). For detection of QTc prolongation, awECG lead V5 had the best specificity (94.4% and 87.5%, respectively) and positive predictive value (87.5% and 80.0%, respectively), and for identification of patients with LQTS, awECG leads II and V5 had the greatest specificity (92.3%-94.1%) and positive predictive value (85.7% to 91.7%) in both males and females., Conclusions: Apple Watch leads II and V5 tracings can be used for reproducible and accurate measurement of QTc interval, ascertainment of abnormal T wave morphologies, and detection of prolonged QTc interval in children and adolescents with LQTS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)