Girolami Francesca, Spinelli Valentina, Maurizi Niccolò, Focardi Martina, Nesi Gabriella, Maio Vincenza, Grifoni Rossella, Albora Giuseppe, Bertaccini Bruno, Targetti Mattia, Coppini Raffaele, Favilli Silvia, Olivotto Iacopo, Cerbai Elisabetta
Cardiology Unit, Meyer Children's University Hospital, Florence, Italy.
Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Front Cardiovasc Med. 2022 Dec 14;9:1080608. doi: 10.3389/fcvm.2022.1080608. eCollection 2022.
Sudden cardiac arrest (SCA) in young people represents a dramatic event, often leading to severe neurologic outcomes or sudden cardiac death (SCD), and is frequently caused by genetic heart diseases. In this study, we report the results of the Tuscany registry of sudden cardiac death (ToRSADE) registry, aimed at monitoring the incidence and investigating the genetic basis of SCA and SCD occurring in subjects < 50 years of age in Tuscany, Italy.
Creation of the ToRSADE registry allowed implementation of a repository for clinical, molecular and genetic data. For 22 patients, in whom a genetic substrate was documented or suspected, blood samples could be analyzed; 14 were collected at autopsy and 8 from resuscitated patients after SCA. Next generation sequencing (NGS) analysis revealed likely pathogenetic (LP) variants associated with cardiomyopathy (CM) or channelopathy in four patients (19%), while 17 (81%) carried variants of uncertain significance in relevant genes (VUS). In only one patient NGS confirmed the diagnosis obtained during autopsy: the p.(Asn480Lysfs*20) PKP2 mutation in a patient with arrhythmogenic cardiomyopathy (AC).
Systematic genetic screening allowed identification of LP variants in 19% of consecutive patients with SCA/SCD, including subjects carrying variants associated with hypertrophic cardiomyopathy (HCM) or AC who had SCA/SCD in the absence of structural cardiomyopathy phenotype. Genetic analysis combined with clinical information in survived patients and post-mortem evaluation represent an essential multi-disciplinary approach to manage juvenile SCD and SCA, key to providing appropriate medical and genetic assistance to families, and advancing knowledge on the basis of arrhythmogenic mechanisms in inherited cardiomyopathies and channelopathies.
年轻人心脏骤停（SCA）是一个严重事件，常导致严重的神经系统后果或心源性猝死（SCD），且常由遗传性心脏病引起。在本研究中，我们报告了托斯卡纳心源性猝死登记处（ToRSADE）登记处的结果，旨在监测意大利托斯卡纳地区50岁以下人群中SCA和SCD的发病率，并研究其遗传基础。
ToRSADE登记处的建立允许创建一个临床、分子和遗传数据储存库。对于22例记录或怀疑有遗传底物的患者，可以分析血样；14例在尸检时采集，8例在SCA后复苏的患者中采集。下一代测序（NGS）分析显示，4例患者（19%）存在与心肌病（CM）或离子通道病相关的可能致病（LP）变异，而17例（81%）在相关基因中携带意义不明确的变异（VUS）。只有1例患者的NGS证实了尸检时获得的诊断：1例致心律失常性心肌病（AC）患者存在p.(Asn480Lysfs*20) PKP2突变。
系统的基因筛查能够在19%的连续性SCA/SCD患者中识别出LP变异，包括那些携带与肥厚型心肌病（HCM）或AC相关变异但在无结构性心肌病表型的情况下发生SCA/SCD的患者。对存活患者的基因分析与临床信息以及尸检评估相结合，是管理青少年SCD和SCA的重要多学科方法，对于为家庭提供适当的医疗和遗传援助以及推进对遗传性心肌病和离子通道病心律失常机制的认识至关重要。
