Steinberg Christian, Padfield Gareth J, Champagne Jean, Sanatani Shubhayan, Angaran Paul, Andrade Jason G, Roberts Jason D, Healey Jeffrey S, Chauhan Vijay S, Birnie David H, Janzen Mikyla, Gerull Brenda, Klein George J, Leather Richard, Simpson Christopher S, Seifer Colette, Talajic Mario, Gardner Martin, Krahn Andrew D
For the author affiliations, please see the Appendix.
Circ Arrhythm Electrophysiol. 2016 Sep;9(9). doi: 10.1161/CIRCEP.115.004274.
Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities.
Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims' relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%; P=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%; P=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%).
Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.
不明原因心脏骤停（UCA）可能由遗传性心律失常综合征所解释。心脏骤停幸存者左室射血分数保留注册研究前瞻性评估了UCA患者的一级亲属或不明原因猝死受害者的亲属，以筛查心脏异常情况。
约398名一级家庭成员（186名UCA患者的亲属、212名不明原因猝死受害者的亲属；平均年龄44±17岁）接受了全面的心脏检查，包括心电图、信号平均心电图、运动试验、心脏成像、动态心电图监测，以及使用肾上腺素或普鲁卡因胺进行选择性激发药物试验。当在UCA幸存者中鉴定出突变，或诊断检查显示出提示特定遗传性心律失常综合征的表型时，进行基因检测。根据先前发表的定义，将诊断强度分为明确、很可能或可能。在398例患者中的120例（30.2%）检测到心脏异常，其中398例中有67例有明确或很可能的诊断（17%），包括长QT综合征（13%）、儿茶酚胺能多形性室性心动过速（4%）、致心律失常性右室心肌病（4%）和Brugada综合征（3%）。UCA患者亲属和不明原因猝死受害者亲属的检出率相似（31%对27%；P=0.59）。UCA患者亲属中进行基因检测的比例更高（29%对20%；P=0.03）。在398名亲属中的20名（5%）鉴定出致病突变。最常见的致病突变是RyR2（2%）、SCN5A（1%）和KNCQ1（0.8%）。
心脏筛查在30%的UCA患者或不明原因猝死受害者的一级亲属中发现了异常，17%有明确的有效诊断。长QT综合征、致心律失常性右室心肌病和儿茶酚胺能多形性室性心动过速是最常见的诊断。对无症状个体进行系统的级联筛查和基因检测将导致预防性的生活方式和医疗干预，有可能预防心源性猝死。
