Department of Cardiology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Cardiol Young. 2024 May;34(5):1010-1017. doi: 10.1017/S1047951123003086. Epub 2023 Nov 29.
Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype.
Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V.
The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues.
Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.
儿茶酚胺多形性室性心动过速是一种离子通道病，由编码钙处理蛋白的基因突变引起。它可以与左室致密化不全并存。我们旨在研究这种共表型的临床和遗传特征。
回顾性分析 2005 年 9 月至 2020 年 1 月期间在中国两家医院诊断为儿茶酚胺多形性室性心动过速的 24 例患者的病历。评估其临床和遗传特征，包括基本人口统计学数据、心电图参数、药物治疗和随访期间的生存情况，以及基因突变情况。我们对一种新型的 Ryanodine 受体 2-E4005V 进行了结构分析。
患者包括 19 例儿茶酚胺多形性室性心动过速单表型和 5 例儿茶酚胺多形性室性心动过速-左室致密化不全重叠患者。症状发作的中位年龄为 9.0（8.0，13.5）岁。大多数患者（91.7%）有心脏症状，50%有晕厥家族史。重叠患者在运动应激试验中，室性心动过速和室性早搏的峰值心率和阈心率较低（p < 0.05）。随访期间，重叠患者的心脏性猝死风险可能较高。基因测序显示 1 种新型 Ryanodine 受体 2 错义突变 E4005V 和 1 种儿茶酚胺多形性室性心动过速中未报道的突变，但未观察到左室致密化不全相关突变。计算机模拟分析表明，新型突变 E4005V 破坏了两个带电残基之间的相互作用。
儿茶酚胺多形性室性心动过速与左室致密化不全重叠可能导致运动应激试验时室性早搏/室性心动过速的阈心率低于单纯儿茶酚胺多形性室性心动过速；也可能预示着预后更差，需要严格随访。Ryanodine 受体 2 突变破坏了残基之间的相互作用，可能干扰 Ryanodine 受体 2 的功能。
