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The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this seventh section of the report offers a comprehensive analysis of disorders of heart rhythm in China. In 2021, China has achieved significant development and gratifying results in many aspects of the field of arrhythmia. Left bundle branch pacing (LBBP), as an emerging pacing technique originating from China, has received widespread attention. New research results have emerged on its indications, surgical procedures, clinical evaluation, and comparison with other pacing techniques. Its feasibility, effectiveness, and safety have been basically verified, but its long-term prognosis still needs further confirmation from larger samples and longer follow-up time research results. Leadless pacemakers have begun to be used in a wider range of clinical applications, and related large sample cohort studies have been reported. In addition, there are also noteworthy new achievements in the fields of pacemaker remote programming, anticoagulation and radiofrequency catheter ablation (RFCA) therapy for atrial fibrillation, and implantable cardioverter defibrillator prevention of sudden cardiac death. In terms of clinical practice, due to COVID-19 pandemic, the number of RFCA procedures and other device implantations in China has fluctuated, but it has gradually recovered since 2020. [ABSTRACT FROM AUTHOR]

Background: Cenani‐Lenzsyndactyly syndrome (CLSS; OMIM 212780) is a rare autosomal recessive acral deformity, which is mainly manifested in the fusion of fingers or toes, disordered phalangeal structure, shortening or fusion of the radius and ulna, and renal hypoplasia. Case presentation: Our report described an individual with mild phenotypes from China. His parents were not consanguineous. The affected individual was non‐dysmorphic. Standard X‐ray showed that the both hands have only four metacarpal bones. The distal end of the first metacarpal bone on the right was relatively slender, and the distal phalanx was absent. Multiple phalanges and some soft tissues of both hands were fused. Exome sequencing revealed a novel biallelic c.282C⟩Avariant in low‐density lipoprotein receptor‐related protein 4 (LRP4; OMIM604270; NM_002334.4) causing p. (Asn94Lys) change in the encoded protein. This variant is predicted to be potentially pathogenic, affecting protein structure and function. Conclusion: We report a novel missense variant present in homozygosity in LRP4 to broaden the pathogenic spectrum of LRP4 in syndactyly, and exome sequencing technology is a powerful tool for genetic analysis in prenatal diagnosis and medical research, as a preferred method for the diagnosis of syndactyly and related phenotypes. [ABSTRACT FROM AUTHOR]

The hard-shell mussel (Mytilus coruscus) is widespread in the temperate coastal areas of the northwest Pacific and holds a significant position in the shellfish aquaculture market in China. However, the natural resources of this species have been declining, and population genetic studies of M. coruscus are also lacking. In this study, we conducted whole-genome resequencing (WGR) of M. coruscus from eight different latitudes along the Chinese coast and identified a total of 25,859,986 single nucleotide polymorphism (SNP) markers. Our findings indicated that the genetic diversity of M. coruscus from the Zhoushan region was lower compared with populations from other regions. Furthermore, we observed that the evolutionary tree clustered into two primary branches, and the Zhangzhou (ZZ) population was in a separate branch. The ZZ population was partly isolated from populations in other regions, but the distribution of branches was not geographically homogeneous, and a nested pattern emerged, consistent with the population differentiation index (FST) results. To investigate the selection characteristics, we utilized the northern M. coruscus populations (Dalian and Qingdao) and the central populations (Zhoushan and Xiangshan) as reference populations and the southern ZZ population as the target population. Our selection scan analysis identified several genes associated with thermal responses, including Hsp70 and CYP450. These genes may play important roles in the adaptation of M. coruscus to different living environments. Overall, our study provides a comprehensive understanding of the genomic diversity of coastal M. coruscus in China and is a valuable resource for future studies on genetic breeding and the evolutionary adaptation of this species. [ABSTRACT FROM AUTHOR]

Genetic testing is used for the diagnosis and risk stratification of Brugada syndrome (BrS), but few studies have systematically evaluated regional differences and variations of its use worldwide. This study investigated the rates and yields of genetic testing reported by various BrS cohorts. PubMed was searched systematically for cohort studies on BrS patients between January 2002 and April 2022. Of the 60 studies identified, 20 studies contained relevant information. In total, the rate of genetic testing is 59.4% with a yield of 26.3%. The highest rate of genetic testing of 100% was achieved by some centers in China, Japan, France, and Spain, while the lowest rate of genetic testing of 10% was observed in Hong Kong, China. The highest yield of 67% was reported in a Belgium center, while the lowest yield of 10% was reported by centers from Japan. Together this study highlights the variations in both the percentage of patients undergoing genetic testing and its percentage yield. [ABSTRACT FROM AUTHOR]

Background. Brugada syndrome is a hereditary cardiac disease associated with mutations in ion channel genes. The clinical features include ventricular fibrillation, syncope, and sudden cardiac death. A family with Brugada syndrome with sudden cardiac death was analyzed to locate the associated mutation in the SCN5A gene. Methods and Results. Three generations of a Han Chinese family with Brugada syndrome were recruited in the study; their clinical phenotype data were collected and DNA samples extracted from the peripheral blood. Next-generation sequencing was carried out in the proband, and candidate genes and mutations were screened using the full exon capture technique. The family members who participated in the survey were tested for possible mutations using Sanger sequencing. Six family members were diagnosed with Brugada syndrome, including four asymptomatic patients. A newly discovered heterozygous mutation in the proband was located in exon 25 of SCN5A (NM_000335.5) at c.4313dup(p.Trp1439ValfsTer32). Among the surviving family members, only those with a Brugada wave on their electrocardiogram carried the c.4313dup(p.Trp1439ValfsTer32) variant. Bioinformatics prediction revealed that the frameshift of the c.4313dup (p.Trp1439ValfsTer32) mutant led to a coding change of 32 amino acids, followed by a stop codon, resulting in a truncated protein product. Conclusion. The newly discovered mutation site c.4313dup(p.Trp1439ValfsTer32) in exon 25 of SCN5A may be the molecular genetic basis of the family with Brugada syndrome. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the leading cause of mortality and morbidity worldwide, Chronic stable angina (CSA) is the main symptom of myocardial ischemia, causes increased risk of major cardiovascular events such as sudden cardiac death and myocardial infarction. Naoxintong (NXT) capsule is a classical traditional Chinese medication used to treat CSA, however, few evidence to support the wide utility of NXT capsule for the treatment of CSA. We design this study to evaluate the efficacy and safety of NXT capsule versus placebo in patients with CSA.Methods/design: This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 260 eligible participants will be enrolled. The participants will be randomized assigned in an equal ratio to groups receiving either NXT or placebo for 12 weeks. After a 2-week run-in period, they will receive either NXT or placebo (3 pills, 3 times daily) for 12 weeks. The primary outcome is therapeutic efficacy. Secondary outcome measures include the quantitative score of TCM syndromes, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of Seattle angina scale, serum homocysteine, and incidence of cardiovascular events. Safety outcomes and adverse events will be monitored throughout the trial.Discussion: We designed this study in accordance with principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide clinical evidence of the efficacy and safety of NXT Capsule in the treatment of CSA.Trial Registration: Chinese Clinical Trial Registry ChiCTR2100044563 . Registered on 24 March 2020. [ABSTRACT FROM AUTHOR]

Objective: To investigate the obesity paradox and its interrelationship with objective physical activity (PA) in patients at high risk of sudden cardiac death.Methods: A total of 782 patients with implantable cardioverter-defibrillators/cardiac resynchronization therapy defibrillators in the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-Implantable Patients registry were retrospectively analyzed and grouped by body mass index (BMI) (kg/m2): normal weight (18.5 ≤ BMI < 25) and overweight or class I obesity (25 ≤ BMI < 35). PA was measured with home monitoring and categorized into 4 groups (Q1-Q4) by the baseline quartiles. The main endpoint was all-cause mortality.Results: During a mean follow-up period of 59.9 ± 21.9 months, 182 all-cause mortality events occurred. Mortality tended to be lower in overweight and obesity patients (18.9% vs 25.1%, P = 0.061) and decreased by PA quartiles (44.1% vs 22.6% vs 15.3% vs 11.2%, Q1-Q4, P < 0.001). Multivariate Cox analysis indicated BMI (hazard ratio, 0.918; 95% confidence interval, 0.866-0.974; P = 0.004) and PA (0.436, 0.301-0.631, Q2 vs Q1; 0.280, 0.181-0.431, Q3 vs Q1; 0.257, 0.158-0.419, Q4 vs Q1; P < 0.001 for all) were associated with reduced risk. The obesity paradox was significant in the total cohort (log rank P = 0.049) and low PA group (log rank P = 0.010), but disappeared in the high PA group (log rank P = 0.692). Dose-response curves showed a significant reduction in risk with low-moderate PA, and the pattern varied between different BMI groups.Conclusions: The obesity paradox only persisted in physically inactive patients. PA might be related to the development of the obesity paradox. [ABSTRACT FROM AUTHOR]

Objective: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy-related mortality in young adults. It has been suggested that SUDEP may kill over 20 000 people with epilepsy in China yearly. The aetiology of SUDEP is unclear. Little is known about candidate genes for SUDEP in people of Chinese origin as most studies have ascertained this in Caucasians. No candidate genes for SUDEP in Chinese people have been identified.Methods: We performed whole exome sequencing (WES) in DNA samples collected from five incident cases of SUDEP identified in a large epilepsy cohort in rural China. We filtered rare variants identified from these cases as well as screened for SUDEP, epilepsy, heart disease or respiratory disease-related genes from previous published reports and compared them with publicly available data, living epilepsy controls and ethnicity-match non-epilepsy controls, to identify potential candidate genes for SUDEP.Results: After the filtering process, the five cases carried 168 qualified mutations in 167 genes. Among these genetic anomalies, we identified rare variants in SCN5A (1/5:20% in our cases), KIF6 (1/5:20% in our cases) and TBX18 (1/5:20% in our cases) which were absent in 330 living epilepsy control alleles from the same original cohort and 320 ethnicity-match non-epilepsy control alleles.Conclusions: These three genes were previously related to heart disease, providing support to the hypothesis that underlying heart disorder may be a driver of SUDEP risk. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation., Methods and Results: A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation-triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5-73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012)., Conclusion: Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Xin Su Ning (XSN) is a China patented and certified traditional Chinese herbal medicine used to treat premature ventricular contractions (PVCs) since 2005. XSN is formulated with 11 herbs, designed to treat arrhythmia with phlegm-heat heart-disturbed syndrome (PHHD) according to Chinese medicine theory. The rational compatibility of the 11 herbs decides the therapeutic outcome of XSN. Due to the multicomponent nature of traditional Chinese medicine, it is difficult to use conventional pharmacology to interpret the therapeutic mechanism of XSN in terms of clear-cut drug molecule and target interactions. Network pharmacology/systematic pharmacology usually consider all the components in a formula with the same weight; therefore, the proportion of the weight of the components has been ignored. In the present study, we introduced a novel coefficient to mimic the relative amount of all the components in relation with the weight of the corresponding herb in the formula. The coefficient is also used to weigh the pharmacological effect of XSN on all relative biological pathways. We also used the cellular electrophysiological data generated in our lab, such as the effect of liensinine and isoliquiritigenin on NaV1.5 channels; we therefore set sodium channel as one of the targets of these two components, which would support the clinical efficacy of XSN in treating tachyarrhythmia. Combining the collected data and our discovery, a panoramagram of the pharmacological mechanism of XSN was established. Pathway enrichment and analysis showed that XSN treated PHHD arrhythmia through multiple ion channels regulation, protecting the heart from I/R injury, inhibiting the apoptosis of cardiomyocyte, and improving glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). Risk predictive scores were previously developed with various performances., Objective: The purpose of this study was to create a novel score-Predicting Arrhythmic evenT (PAT)-with internal and external validation., Methods: A systematic review was performed to identify risk factors for MAE. The odds ratios (ORs) of each factor were pooled across studies. The PAT scoring scheme was developed based on pooled ORs. The PAT score was internally validated with published 105 Asian patients (follow-up 8.0 ± 4.1 [SD] years) and externally validated with unpublished 164 multiracial patients (82.3% White, 14.6% Asian, 3.2% Black; mean follow-up 8.0 ± 6.9 years) with Brugada syndrome. Performances were assessed and compared with previous scores using receiver operating characteristic curve (ROC) analysis., Results: Sixty-seven studies published between 2002 and 2022 from 26 countries (7358 patients) were included. Pooled ORs were estimated, indicating that 15 of 23 risk factors were significant. The PAT score was then developed accordingly. The PAT score had significantly better discrimination (ROC 0.9671) than the BRUGADA-RISK score (ROC 0.7210; P = .006), Shanghai Score System (ROC 0.7079; P = .003), and Sieira et al score (ROC 0.8174; P = .026) in an external validation cohort. PAT score ≥ 10 predicted the first MAE with 95.5% sensitivity and 89.1% specificity (ROC 0.9460) and the recurrent MAE (ROC 0.7061) with 15.4% sensitivity and 93.3% specificity., Conclusion: The PAT score was shown to be useful in predicting MAE for primary prevention in patients with Brugada syndrome., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG., Methods and Results: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone., Conclusion: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The exact world-wide prevalence of Brugada electrocardiogram (ECG) pattern is still unclear, especially in adults aged 55 years and older.Methods and Results: The study was conducted as part of the Healthy Aging Longitudinal Study in Taiwan (HALST). Using a stratified random sampled method, a sample of community-dwelling subjects was recruited from seven community-based regions across Taiwan. All enrolled subjects were follow-up annually and cause of death was documented by citizen death records. A total of 5214 subjects were enrolled (male/female: 2530/2684) with a mean age of 69 ± 8 years. The overall prevalence of Brugada ECG patterns was 3.32%. Four subjects carried spontaneous Type 1 Brugada ECG pattern, 68 carried Type 2, and 101 carried Type 3. Compared with the world-wide average prevalence of Brugada ECG patterns, the prevalence of spontaneous Type 1 Brugada ECG pattern in subjects from the HALST cohort was similar (0.077 vs. 0.07%) and the combined prevalence of Types 2 and 3 Brugada ECG pattern was 10 times higher (3.24 vs. 0.28%) even the mean age of study subjects was significantly higher (69 ± 8 vs. 35 ± 8, P < 0.001). However, all-cause mortality and cardiac mortality rates were not significantly different between subjects with and without Brugada ECG patterns during the 4-year follow-up (log-rank test, P = 0.21, 0.32, respectively).Conclusion: The prevalence of Brugada ECG pattern in adults aged 55 years and older in Taiwan was higher than the average world-wide prevalence but was not associated with increased mortality. [ABSTRACT FROM AUTHOR]

Sudden unexplained nocturnal death syndrome (SUNDS) remains an enigma to both forensic pathologists and physicians. Previous epidemiological, clinical, and pilot genetic studies have implicated that SUNDS is most likely a disease allelic to Brugada syndrome (BrS). We have performed postmortem genetic testing to address the spectrum and role of genetic abnormalities in the SCN5A-encoded cardiac sodium channel and its several associated proteins in SUNDS victims from Southern China. Genomic DNA extracted from the blood samples of 123 medico-legal autopsy-negative SUNDS cases and 104 sex-, age- and ethnic-matched controls from Southern China underwent comprehensive amino acid coding region mutational analysis for the BrS associated genes SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, MOG1, and GPD1-L using PCR and direct sequencing. We identified a total of 7 unique (4 novel) putative pathogenic mutations (all in SCN5A; V95I, R121Q [2 cases], R367H, R513H, D870H, V1764D, and S1937F) in 8/123 (6.5%) SUNDS cases. Three SCN5A mutations (V95I, R121Q, and R367H) have been previously implicated in BrS. An additional 8 cases hosted rare variants of uncertain clinical significance (SCN5A: V1098L, V1202M, R1512W; SCN1B: V138I [3 cases], T189M [2 cases]; SCN3B: A195T). There were no nonsynonymous mutations found in SCN2B, SCN4B, MOG1, or GPD1-L. This first comprehensive genotyping for SCN5A and related genes in the Chinese Han population with SUNDS discovered 13 mutations, 4 of them novel, in 16 cases, which suggests cardiac sodium channel dysfunction might account for the pathogenesis of 7-13% of SUNDS in Southern China. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS)., Methods: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used., Results: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index., Conclusions: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The J wave has been seen in idiopathic ventricular fibrillation, Brugada syndrome, and early repolarization syndrome. Although these conditions share some ECG features, the clinical consequences are markedly different. J wave presentation in healthy subjects is not a rare phenomenon, although its characteristics are poorly understood. The aim of this study was to investigate the prevalence and the characteristics of the J wave in apparently healthy Chinese adults. Methods: The study was comprised of 1817 consecutive healthy Chinese subjects undergoing annual routine medical examination from April 2006 to July 2006, including 1131 men and 686 women. Routine medical examination including ECG was performed. J wave was defined as a wave on the ECG that followed the QRS complex with amplitude of at least 0.05 mV for 0.03 sec. Results: The prevalence of the J wave in all subjects was 7.26%. The prevalence of the J wave in males was significantly higher than in females (10.52 vs. 1.89%, p <0.01). The incidence of the J wave in the inferior leads (II, III, avF), right precordial leads (V1–V3), and left precordial leads (V4–V6) was 4.57, 0.50, and 2.20%, respectively. The J wave prevalence in the inferior leads was significantly higher than in the left and right precordial leads (both p <0.05). Moreover, the prevalence of the J wave had a positive correlation with age in all subjects (r = 0.78, p <0.01). Conclusions: J wave presentation on the ECG of apparently healthy people is not a rare phenomenon and is more likely to be found in the elderly, in males, and more frequently occurs in the inferior leads than in left and right precordial leads. [Copyright &y& Elsevier]

Background: The Shanghai Score System, which weighs electrocardiogram (ECG) findings reflecting repolarization abnormalities, has been proposed for diagnosis of early repolarization syndrome (ERS). However, recent studies have suggested the involvement of depolarization abnormalities in some ERS patients. The aim of this study was to validate the Shanghai Score System in predicting the recurrence of ventricular fibrillation (VF) in ERS patients. The predictive value of fragmented QRS (fQRS) was also investigated., Methods: Fifteen consecutive ERS patients (14 males, median age of 47 years) with a history of VF were retrospectively reviewed. The Shanghai Score System points were calculated, and the presence of fQRS was evaluated., Results: During the median follow-up period of 79.2 months, five patients experienced VF recurrence. In the VF recurrence group, two patients showed augmented amplitude of J waves with horizontal ST-segment, while the other three patients had dynamic changes in J-wave amplitude. The Shanghai Score System points in the VF recurrence group were higher than those in the VF non-recurrence group (6.5 [range: 5.8-6.8] vs. 4.5 [range: 4.0-4.5], p = 0.002). The presence of fQRS on standard 12-lead ECG was more frequently observed in the VF recurrence group compared with the non-recurrence group (100% vs. 10%, p = 0.002)., Conclusions: The present study demonstrated that the Shanghai Score System could effectively identify ERS patients at high risk for VF recurrence. The results also suggested that the presence of fQRS, a marker of depolarization abnormalities, may be useful for predicting VF recurrence in ERS patients., (© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: The purpose of this study was to prospectively recruit patients treated with limb malformation and to explore the prevalence and the clinical and epidemiological features of Heart-Hand Syndrome (HHS) in China.Methods: The consecutive patients treated for congenital upper limb malformation in Beijing Ji Shui Tan Hospital from October 1st, 2016 to October 1st, 2019 were prospectively recruited. We reviewed the patients' medical records and identified patients with abnormal electrocardiogram (ECG) and/or abnormal ultrasonic cardiogram as well as their basic demographic and clinical characteristics.Results: A total 1653 (1053 male and 600 female) patients with congenital upper extremity malformations were prospectively recruited. Among them, 200 (12.1%) had abnormal ultrasonic cardiogram (181patients, 10.9%) and/or abnormal ECG (19 patients, 1.1%). The commonest type of abnormal heart structure was atrial septal defect (69/181 38.1%), and the commonest abnormal ECG was wave patterns (7/19, 36.8%). HHS patients had a higher comorbidity rate (11%) than non-HHS patients (6.9%). Patients with HHS were classified into four groups by the types of congenital upper extremity malformations, among which the most common group was thumb type (121/200, 60.5%).Conclusions: HHS occurred frequently among patients with congenital upper extremity malformation in China, particularly for those with multiple congenital malformations. The commonest type of hand malformations of HHS patients was thumb malformation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the presence of Brugada electrocardiogram (ECG) pattern, clinical characteristics, treatment, and long-term prognosis of Brugada syndrome in southern Chinese population., Methods: This prospective study consisted of a consecutive series of patients with diagnostic coved type I Brugada ECG pattern at baseline between January 2007 and February 2020. Histories of symptoms including ventricular tachycardia (VT)/ventricular fibrillation (VF) episode, syncope, and family history of Brugada Syndrome (BrS) or unexplained sudden cardiac death were collected. Electrophysiological study and implantable cardioverter-defibrillator (ICD) were performed. All patients included in this study were followed up in the outpatient department every 6 months after baseline evaluation. Occurrences of syncope, VF, and sudden death were independently analyzed by two cardiologists., Results: 45 (56.3%) patients were diagnosed with BrS. During a mean follow-up of 7.9 ± 3.6 years, six patients had experienced documented VF/sudden cardiac death (SCD) or recurrent syncope. Two patients experienced episodes of syncope more than once. Two patients experienced onset of electrical storm with a total of 11 episodes of VF. There were 50% of these events occurring in fever status. One of patient with BrS died of SCD., Conclusion: There was a very low prevalence of Brugada syndrome in southern Chinese population. The risk of arrhythmic events was low in asymptomatic patients. ICD was high effective in preventing SCD without adverse device outcome in long-term follow-up. Fever can lead to predispose to malignant arrhythmia, and aggressive treatment of febrile state in Brugada syndrome was recommended., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Aims: Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores., Methods and Results: A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67-0.79) and 0.71 (0.61-0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P < 0.01). No statistical difference was found in intermediate-risk patients (score 2-4). The Shanghai score does not allow to better stratify the risk of SCA., Conclusions: In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Atrial electrophysiological abnormalities have previously been reported in Brugada syndrome. We investigated the incidence and electrocardiographic predictors of atrial fibrillation (AF) in a Chinese cohort of Brugada syndrome patients., Methods: A retrospective study of Brugada syndrome patients admitted to tertiary centers in Hong Kong., Results: A total of 275 patients were included (median age at presentation: 53 [40-64], 247 (90%) males) with a median follow-up duration of 67 (31-113) months. A total of 14 patients (5%) developed AF. Inter-atrial block and AV block were found in 36% (n = 100) and 13% (n = 37) of all patients. Compared to those in sinus rhythm, patients with AF showed significantly longer P-wave duration (PWD) (125 [116-137] vs. 114 [106-124] ms, P = 0.009) and PR interval (190 [163-214] vs. 169 [153-184] ms; P = 0.023). They were more likely to develop syncope (79 vs. 43%; P = 0.012) or VT/VF (43 vs. 14%; P = 0.012), undergo electrophysiological studies (36 vs. 19%; P = 0.005) and receive ICDs (71 vs. 25%; P = 0.001). Univariate logistic regression showed that mean PWD (odds ratio [OR]: 1.03 [1.00-1.06], P = 0.021), PR interval (OR: 1.02 [1.01-1.04]; P = 0.010) and QT interval (OR: 1.02 [1.00-1.04], P = 0.012), syncope (OR: 4.80 [1.31-17.61], P = 0.018) and R-wave amplitude in lead V5 (OR: 0.30 [0.09-1.00]; P = 0.05) significantly predicted incident AF. Receiver operating characteristic analysis revealed an optimum cut-off point of 123 ms and area under the curve of 0.71 for PWD., Conclusion: The incidence of AF was 5% in this cohort. PWD, PR and QT intervals significantly predicted AF and are simple electrocardiographic markers for identifying potential at-risk patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unclear etiology. Arrhythmia has been implicated in SUNDS. Mutations/deficiencies in intercalated disc components have been shown to cause arrhythmias. Human cardiomyopathy-associated 1 (XIRP1) and 3 (XIRP2) are intercalated disc-associated, Xin repeats-containing proteins. Mouse Xirp1 is necessary for the integrity of intercalated disc and for the surface expression of transient outward and delayed rectifier K + channels, whereas mouse Xirp2 is required for Xirp1 intercalated disc localization. Thus, XIRP1 and XIRP2 may be potentially causal genes for SUNDS., Methods and Results: We genetically screened XIRP genes in 134 sporadic SUNDS victims and 22 Brugada syndrome (BrS) cases in a Chinese Han population. We identified 16 rare variants (6 were in silico predicted as deleterious) in SUNDS victims, including a novel variant, XIRP2-E215K. There were also four rare variants (2 were in silico predicted as deleterious) detected in BrS cases, including a novel variant, XIRP2-L2718P. Interestingly, among these 20 variants, we detected 2 likely pathogenic variants: a nonsense variant (XIRP2-Q2875*) and a frameshift variant (XIRP2-T2238QfsX7). Analyzing available Xirp2 knockout mice, we further found that mouse hearts without Xirp2 exhibited prolonged PR and QT intervals, slow conduction velocity, atrioventricular conduction block, and an abnormal infranodal ventricular conduction system. Whole-cell patch-clamp detected altered ionic currents in Xirp2 -/- cardiomyocytes, consistent with the observed association between Xirp2 and Nav1.5/Kv1.5 in co-immunoprecipitation., Conclusions: This is the first report identifying likely pathogenic XIRP rare variants in arrhythmogenic disorders such as SUNDS and Brugada syndrome, and showing critical roles of Xirp2 in cardiac conduction., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unknown etiology to both forensic pathologists and physicians. The electrocardiogram (ECG) characteristics and clinical phenotype of SUNDS survivors strongly suggest that SUNDS shares some similarities with Brugada syndrome (BrS). Recently, the variants of sodium channel Na v 1.8 coding gene SCN10A were identified to be associated with BrS. Here, we investigated the association of SCN10A gene variants with 105 sporadic SUNDS victims and 22 BrS cases in the Chinese Han population. A total of 6 rare mutations and 16 polymorphisms were detected in SUNDS victims. Of the six rare mutations, two were putative pathogenic mutations (F386C and R1263*), one was a likely pathogenic mutation (R14H), and the other three were predicted as benign (R817Q, T1181M, and P1683S). As for the 16 polymorphisms, 1 was a novel polymorphism (c.4144-84G>A) located in intron 24, and the rest were reported previously including one polymorphism (c.2884A>G [I962V]) which showed a statistically significant difference in allele frequency (p = 0.044) between SUNDS and the control group. There were also 5 rare mutations and 15 polymorphisms detected in BrS cases. This is the first report of common and rare variants of SCN10A gene in SUNDS and BrS in the Chinese Han population, which provides the genetic epidemiological evidence that SCN10A may be a novel susceptibility gene for SUNDS and account for approximately 3 % of SUNDS in China.

Background: Catheter ablation in the right ventricular outflow tract (RVOT) may modify the electrophysiologic substrate for recurrent ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS)., Objective: The purpose of this study was to investigate the mechanism and arrhythmogenic substrate of VT/VF and to evaluate the long-term outcomes of catheter ablation in patients with BrS., Methods: Eleven consecutive patients with BrS referred to 2 academic medical centers underwent combined epicardial-endocardial electroanatomic mapping. Catheter ablation was performed in regions of localized conduction slowing. Transmural dispersion of late activation was calculated as the difference between the latest activation between epicardium and endocardium, and low-voltage areas were analyzed., Results: Eleven patients met diagnostic criteria for BrS (spontaneous type 1, n = 9; Na channel provocation = 2). All patients were found to have a localized region in the anterior epicardial RVOT with conduction slowing evidenced by prolonged electrogram duration (78.79 ± 19.87 ms vs 58.93 ± 10.11 ms in epicardial right ventricle, and 59.87 ± 12.61 ms in endocardial RVOT, P <.005, respectively) with variable low voltage (0.97 ± 0.48 mV; median scar area 19.8 ± 25.9 cm 2 ). Epicardial ablation resulted in normalization of spontaneous type 1 Brugada ECG pattern in all patients, and 73% were free from VT/VF at 25 ± 11 months., Conclusion: Prolonged electrograms localized to epicardial RVOT with variable low voltage were identified in all patients with BrS. J-point and ST-segment elevation correlated with greater transmural dispersion of late activation and was independent of total low-voltage area. Despite normalization of spontaneous type 1 pattern in all patients after ablation, recurrence was still observed, suggesting the implantable cardioverter-defibrillator as the cornerstone therapy for BrS., (Copyright © 2016 Heart Rhythm Society. All rights reserved.)

Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Desmoplakin (DSP) gene was the first desmosomal gene linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which was associated with sudden death. To identify the genetic variants of the DSP gene in SUNDS in the southern Chinese Han population, we genetically screened the DSP gene in 40 sporadic SUNDS victims, 16 Brugada syndrome (BrS) patients, and 2 early repolarization syndrome (ERS) patients using next generation sequencing (NSG) and direct Sanger sequencing. A total of 10 genetic variants of the DSP gene were detected in 11 cases, comprised of two novel missense mutations (p.I125F and p.D521A) and eight previously reported rare variants. Of eight reported variants, two were previously considered pathogenic (p.Q90R and p.R2639Q), three were predicted in silico to be pathogenic (p.R315C, p.E1357D and p.D2579H), and the rest three were predicted to be benign (p.N1234S, p.R1308Q, and p.T2267S). This is the first report of DSP genetic screening in Chinese SUNDS and Brugada syndrome. Our results imply that DSP mutations contribute to the genetic cause of some SUNDS victims and maybe a new susceptible gene for Brugada syndrome.

Background: Idiopathic ventricular arrhythmias (VAs) originating from the pulmonary sinus cusp (PSC) have not been sufficiently clarified., Objectives: The goal of this study was to investigate the prevalence, electrocardiographic characteristics, mapping, and ablation of idiopathic VAs arising from the PSC., Methods: Data were analyzed from 218 patients undergoing successful endocardial ablation of idiopathic VAs with a left bundle branch block morphology and inferior axis deviation., Results: Twenty-four patients had VAs originating from the PSC. In the first 7 patients, initial ablation performed in the right ventricular outflow tract failed to abolish the clinical VAs but produced a small change in the QRS morphology in 3 patients. In all 24 patients, the earliest activation was eventually identified in the PSC, at which a sharp potential was observed preceding the QRS complex onset by 28.2 ± 2.9 ms. The successful ablation site was in the right cusp (RC) in 10 patients (42%), the left cusp (LC) in 8 (33%), and the anterior cusp (AC) in 6 (25%). Electrocardiographic analysis showed that RC-VAs had significantly larger R-wave amplitude in lead I and a smaller aVL/aVR ratio of Q-wave amplitude compared with AC-VAs and LC-VAs, respectively. The R-wave amplitude in inferior leads was smaller in VAs localized in the RC than in the LC but did not differ between VAs from the AC and LC., Conclusions: VAs arising from the PSC are not uncommon, and RC-VAs have unique electrocardiographic characteristics. These VAs can be successfully ablated within the PSC., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the clinical characteristics, treatment methods and outcomes in Chinese non ST-segment elevation acute coronary syndrome (NSTE-ACS) patients from two large clinical trials in different time periods., Methods: All Chinese NSTE-ACS patients from two large International clinical trials (OASIS Registry and TIMACS) underwent coronary artery angiography after first admission were recruited in our analysis. The follow-up time was 180 days. A total of 1 473 NSTE-ACS patients were recruited in this analysis, in which 749 from Organization to Assess Strategies for Ischemic Syndromes (OASIS REISTRY) that completed in 38 centers in China from April 1999 to December 2000, and the rest 724 patients from The Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial in 24 centers in China performed from April 2007 to June 2008., Results: Compared to OASIS patients, TIMACS group were older ((64.2 ± 10.1) years old vs. (58.7 ± 10.2) years old) , and fewer male patients (66.3% (480/724) vs. 74.4% (557/749)) , lower blood pressure at admission, and more histories of previous PCI (9.4% (68/724 vs. 6.4% (48/749)), stroke (8.8% (64/724) vs. 5.1% (38/749)) , hypertension (62.8% (455/724) vs. 56.6% (424/749)) and diabetes (23.3% (169/724) vs. 16.2% (121/749)), lower histories of coronary artery disease (37.4% (271/724) vs. 59.1% (443/749)) and myocardial infarction (12.0% (87/724) vs. 27.6% (207/749)) (all P < 0.05). After admission, comparing to OASIS group, TIMACS patients had significant higher PCI proportion (74.9% (524/724) vs. 49.3% (369/749), P < 0.001). In addition, for secondary prevention, TIMACS patients had significant higher standard medication treatment proportion during hospitalization, at discharge and at 180 days follow up than OASIS group (P < 0.05 for β-blocker, ACEI/ARB and lipid lowering drugs) and higher compliance rate. The combined primary outcome event rate at 180 days was much lower in TIMACS than in OASIS patients (13.3% (96/724) vs. 25.2% (189/749), P < 0.001) mostly due to the reduction on the refractory angina (5.2% (38/724) vs. 22.6% (169/749), P < 0.001) ., Results: of COX regression model adjusted for baseline levels and treatment during hospitalization showed that the incidence rate of combination endpoint (HR = 0.39, 95% CI: 0.29-0.53, P < 0.001) and refractory ischemia/angina rehospitalization (HR = 0.17, 95% CI: 0.11-0.25, P < 0.001) were both lower in TIMACS patients than in OASIS patients., Conclusion: PCI procedure and secondary prevention medication administration are more often applied in TIMACS patients than in OASIS group, which is related to less integrated incidence of primary outcomes reflecting progress in Chinese medical care for non ST elevated acute coronary syndrome patients according to the updated guidelines.