Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia caused by mutations in the ryanodine receptor type 2 (RyR2). Diagnosis of CPVT often occurs after a major cardiac event, thus posing a severe threat to the patient's health. Methods: Publication databases, including PubMed, Scopus, and Embase, were searched for articles on patients with RyR2-CPVT mutations and their associated clinical presentation. Articles were reviewed by two independent reviewers and mutations were analyzed for demographic information, mutation distribution, and therapeutics. The human RyR2 cryo-EM structure was used to model CPVT mutations and predict the diagnosis and outcomes of CPVT patients. Findings: We present a database of 1008 CPVT patients from 227 papers. Data analyses revealed that patients most often experienced exercise-induced syncope in their early teenage years but the diagnosis of CPVT took a decade. Mutations located near key regulatory sites in the channel were associated with earlier onset of CPVT symptoms including sudden cardiac death. Interpretation: The present study provides a road map for predicting clinical outcomes based on the location of RyR2 mutations in CPVT patients. The study was partially limited by the inconsistency in the depth of information provided in each article, but nevertheless is an important contribution to the understanding of the clinical and molecular basis of CPVT and suggests the need for early diagnosis and creative approaches to disease management.

中文翻译：

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兰尼碱受体 2 型突变的位置可预测儿茶酚胺能多形性室性心动过速猝死的发病年龄。基于案例的文献的系统回顾和荟萃分析

背景：儿茶酚胺能多形性室性心动过速 (CPVT) 是一种罕见的遗传性心律失常，由 2 型兰尼碱受体 (RyR2) 突变引起。CPVT 的诊断通常发生在重大心脏事件之后，从而对患者的健康构成严重威胁。方法：检索出版数据库（包括 PubMed、Scopus 和 Embase），查找有关 RyR2-CPVT 突变患者及其相关临床表现的文章。文章由两名独立审稿人审阅，并对突变进行人口统计信息、突变分布和治疗分析。人类 RyR2 冷冻电镜结构用于模拟 CPVT 突变并预测 CPVT 患者的诊断和结果。研究结果：我们提供了来自 227 篇论文的 1008 名 CPVT 患者的数据库。数据分析显示，患者最常在青少年时期经历运动诱发的晕厥，但 CPVT 的诊断花了十年时间。位于该通道关键调节位点附近的突变与早期出现 CPVT 症状（包括心源性猝死）有关。解释：本研究提供了根据 CPVT 患者 RyR2 突变位置预测临床结果的路线图。该研究在一定程度上受到每篇文章提供的信息深度不一致的限制，但仍然对理解 CPVT 的临床和分子基础做出了重要贡献，并表明需要早期诊断和创造性的疾病管理方法。