N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility

Cardiac-specific deletion of the murine gene (Cdh2) encoding the cell adhesion molecule, N-cadherin, results in disassembly of the intercalated disc (ICD) structure and sudden arrhythmic death. Connexin 43 (Cx43)-containing gap junctions are significantly reduced in the heart after depleting N-cadherin, therefore we hypothesized that animals expressing half the normal levels of N-cadherin would exhibit an intermediate phenotype. We examined the effect of N-cadherin haploinsufficiency on Cx43 expression and susceptibility to induced arrhythmias in mice either wild-type or heterozygous for the Cx43 (Gja1)-null allele. An increase in hypophosphorylated Cx43 accompanied by a modest decrease in total Cx43 protein levels was observed in the N-cadherin heterozygous mice. Consistent with these findings N-cadherin heterozygotes exhibited increased susceptibility to ventricular arrhythmias compared to wild-type mice. Quantitative immunofluorescence microscopy revealed a reduction in size of large Cx43-containing plaques in the N-cadherin heterozygous animals compared to wild-type. Gap junctions were further decreased in number and size in the N-cad/Cx43 compound heterozygous mice with increased arrhythmic susceptibility compared to the single mutants. The scaffold protein, ZO-1, was reduced at the ICD in N-cadherin heterozygous cardiomyocytes providing a possible explanation for the reduction in Cx43 plaque size. These data provide further support for the intimate relationship between N-cadherin and Cx43 in the heart, and suggest that germline mutations in the human N-cadherin (Cdh2) gene may predispose patients to increased risk of cardiac arrhythmias.     

302例登革热心电图特征研究

目的 分析登革热患者心电图的特征。方法 回顾性分析302例登革热患者（登革热组）和同期300名健康体检者（对照组）的临床资料,对比2组心电图异常情况;进一步分析异常心电图治疗前后的变化及其特点。结果 登革热组存在心电图异常的患者比例（51.32%,155/302）高于对照组（31.00%,93/300）（P < 0.001）;登革热组心电图异常发生频率高于对照组的有ST-T改变（27.81%,84/302）、窦性心动过缓（11.92%,36/302）（P均< 0.05）;有46例心电图异常的患者治疗后复查了心电图,其中窦性心动过缓发生频率较治疗前下降,差异有统计学意义（P < 0.05）;窦性心动过缓的患者共36例,16例（44.44%）合并ST-T改变,高于无窦性心动过缓的患者（25.56%,68/266）,差异有统计学意义（P < 0.05）。结论 登革热患者心电图异常较普遍,主要表现为ST-T改变、窦性心动过缓;窦性心动过缓是登革热最常见的心律失常和较显著的心电图特征,可能有助于诊断登革热。     

Lengthier cryoablation and a bonus cryoapplication is associated with improved efficacy for cryothermal catheter ablation of supraventricular tachycardias in children

Introduction Cryoablation is an effective treatment for children with supraventricular tachycardias (SVT). The present study documents the effect of two different cryoablation protocols on acute and chronic success rates. Methods and results Fifty-three consecutive patients (age range, 5–20 years) were treated; patients 1 to 17 were treated by a standard ablation protocol and patients 18 to 53 were treated by a modified ablation protocol that required lengthier cryoablations plus delivery of a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention. Electrophysiological study (EPS) was performed with diagnostic catheters and cryoablations were performed with a 7FR 4 mm tip catheter (CryoCath Technologies). Acute endpoints for non-inducibility of atrioventricular nodal re-entrant tachycardia (AVNRT) by programmed atrial stimulation at baseline or during isoproterenol performed 30 min post procedure, as well as non-inducibility and conduction block over the accessory pathway (AP). The chronic endpoint was arrhythmia recurrence post intervention. No permanent cryo-related complications or adverse outcomes were reported. Acute success rates for patients 1 to 17 and 18 to 53 were 88 and 100%, respectively. The cumulative percentage of patients without arrhythmia recurrence at 12 month follow-up was significantly different at 73 and 90%, respectively. Conclusions Lengthier cryoablation delivery, approximating 7 min per cryoablation, increases the acute success rate at intervention. Moreover, these lengthier cryoablation deliveries plus a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention may also significantly improve the chronic success rate, while also maintaining an excellent safety profile for cryoablation treatment of children with SVT such as AVNRT and AP located near the AV junction.     

In situ Ca2+ dynamics of Purkinje fibers and its interconnection with subjacent ventricular myocytes

Purkinje fibers play essential roles in impulse propagation to the ventricles, and their functional impairment can become arrhythmogenic. However, little is known about precise spatiotemporal pattern(s) of interconnection between Purkinje-fiber network and the underlying ventricular myocardium within the heart. To address this issue, we simultaneously visualized intracellular Ca(2+) dynamics at Purkinje fibers and subjacent ventricular myocytes in Langendorff-perfused rat hearts using multi-pinhole type, rapid-scanning confocal microscopy. Under recording of electrocardiogram at room temperature spatiotemporal changes in fluo3-fluorescence intensity were visualized on the subendocardial region of the right-ventricular septum. Staining of the heart with either fluo3, acetylthiocholine iodide (ATCHI), or di-4-ANEPPS revealed characteristic structures of Purkinje fibers. During sinus rhythm (about 60 bpm) or atrial pacing (up to 3 Hz) each Purkinje-fiber exhibited spatiotemporally synchronous Ca(2+) transients nearly simultaneously to ventricular excitation. Ca(2+) transients in individual fibers were still synchronized within the Purkinje-fiber network not only under high-K(+) (8 mM) perfusion-induced Purkinje-to-ventricular (P-V) conduction delay, but also under unidirectional, orthodromic P-V block produced by 10-mM K(+) perfusion. While spontaneous, asynchronous intracellular Ca(2+) waves were identified in injured fibers of Purkinje network locally, surrounding fibers still exhibited Ca(2+) transients synchronously to ventricular excitation. In summary, these results are the first demonstration of intracellular Ca(2+) dynamics in the Purkinje-fiber network in situ. The synchronous Ca(2+) transients, preserved even under P-V conduction disturbances or under emergence of Ca(2+) waves, imply a syncytial role of Purkinje fibers as a specialized conduction system, whereas unidirectional block at P-V junctions indicates a substrate for reentrant arrhythmias.     

Dental management of a patient fitted with subcutaneous Implantable Cardioverter Defibrillator device and concomitant warfarin treatment

Automated Implantable Cardioverter Defibrillators (AICD), simply known as an Implantable Cardioverter Defibrillator (ICD), has been used in patients for more than 30 years. An Implantable Cardioverter Defibrillator (ICD) is a small battery-powered electrical impulse generator that is implanted in patients who are at a risk of sudden cardiac death due to ventricular fibrillation, ventricular tachycardia or any such related event. Typically, patients with these types of occurrences are on anticoagulant therapy. The desired International Normalized Ratio (INR) for these patients is in the range of 2–3 to prevent any subsequent cardiac event. These patients possess a challenge to the dentist in many ways, especially during oral surgical procedures, and these challenges include risk of sudden death, control of post-operative bleeding and pain.This article presents the dental management of a 60 year-old person with an ICD and concomitant anticoagulant therapy. The patient was on multiple medications and was treated for a grossly neglected mouth with multiple carious root stumps. This case report outlines the important issues in managing patients fitted with an ICD device and at a risk of sudden cardiac death.     

Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.     

514例确诊COVID-19患者心电图特征分析

目的：研究新型冠状病毒肺炎住院患者心电图改变和心律失常类型及其与患者临床预后关系。方法：纳入某新冠肺炎专科医院在院患者入院心电图514份,分析其中心电图改变和心律失常类型、特征。结果：254例患者出现明显心电图改变和心律失常,其中窦性心动过速65例（22.2%）,QT间期延长60例（20.5%）,房颤45例（15.4%）,传导阻滞39例（13.3%）,房性早搏22例（7.5%）,室性早搏20例（6.8%）,窦性心律不齐20例（6.8%）,窦性心动过缓18例（6.1%）,预激综合征4例（1.4%）,心律失常发生组患者其在院死亡率显著高于无心律失常组（P＜0.05）。 结论：心律失常多见于老年及合并基础心血管疾病COVID-19患者,其发生与临床预后密切相关。     

卡维地洛抑制大鼠起搏心肌细胞钙库超载诱导的钙释放*

 目的：探讨非选择性β受体阻滞剂卡维地洛对起搏心肌细胞钙库超载诱导钙释放（SOICR）的作用及其机制。方法：电刺激起搏大鼠单个心肌细胞并灌注异丙肾上腺素及咖啡因诱导钙库钙超载,从而触发肌浆网钙释放通道（兰尼碱受体2,RyR2）舒张期开放引起SOICR。应用钙离子荧光成像技术记录胞内钙浓度的实时变化。实验分为对照组、卡维地洛组、美托洛尔组、酚妥拉明组和硝苯地平组。结果：(1) 与基线刺激时比较,对照组细胞灌注异丙肾上腺素和咖啡因后,起搏细胞钙瞬变振幅显著增高（P<0.01）,SOICR的发生率显著增加（P<0.01）。(2) 在1~4 Hz起搏频率下卡维地洛组细胞SOICR发生率分别为2.00%、6.00%、10.00%和16.00%,均显著低于对照组（分别为43.59%、74.36%、87.18%和89.74%,均P<0.01）;卡维地洛对心肌细胞SOICR的抑制在不同起搏频率下无明显差异（P>0.05）。酚妥拉明、美托洛尔和硝苯地平组细胞与对照组细胞比较,SOICR发生率无差异（均P>0.05）。(3) 起搏细胞钙瞬变振幅的比较,各组间相比未见明显差异（P>0.05）;咖啡因峰值估测钙库钙总量的比较,各组间也无明显差异（P>0.05）。结论：卡维地洛可明显抑制起搏心肌细胞SOICR的发生,其作用机制可能是直接抑制RyR2的自发性开放而非源于对α1、β1受体和L型钙通道的阻滞作用。     

心律失常介入治疗数据库平台建设：基本原理和设计方案

背景 临床注册研究是近期国内外学术界兴起的一种新的临床研究形式.美国国家心血管病数据注册系统于2005年开展了针对植入型心律转复除颤器（ICD）的注册.心律失常介入治疗的数据库目的是在依托国家心血管病中心筹建的统一数据库平台基础上,开展植入型器械治疗注册系统和导管消融治疗注册系统.基本原理 根据研究要求,建设我国心律失常介入治疗信息与研究平台的专用网页.建立符合国际标准的电子化、信息化临床研究数据管理和统计分析平台,对研究中各个子项目的数据进行数据监查、数据管理、质量控制及统计分析.设计方案 为前瞻性的、多中心的、开放性注册研究,共有24家医院参加研究.依托国家心血管病中心筹建的统一数据库平台,设计心律失常介入治疗的数据注册系统,包括植入型器械治疗注册系统以及导管消融治疗注册系统.前者包括心脏起搏器、ICD和心脏再同步治疗（CRT）的植入登记数据库和随访数据库.后者包括阵发性室上性心动过速、室性快速心律失常和房性快速心律失常的手术登记数据库和随访数据库.结论 心律失常介入治疗的数据库平台建设将有助于规范心律失常介入治疗的临床行为,实现网络数据库与临床工作平台的合理对接,提高医疗质量和医疗安全.