Mellor Greg, Laksman Zachary W M, Tadros Rafik, Roberts Jason D, Gerull Brenda, Simpson Christopher S, Klein George J, Champagne Jean, Talajic Mario, Gardner Martin, Steinberg Christian, Arbour Laura, Birnie David H, Angaran Paul, Leather Richard, Sanatani Shubhayan, Chauhan Vijay S, Seifer Colette, Healey Jeffrey S, Krahn Andrew D
Circ Cardiovasc Genet. 2017 Jun;10(3). doi: 10.1161/CIRCGENETICS.116.001686.
Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear.
The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6-9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1-9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%; =0.04) but was associated with more variants of unknown significance (55% versus 5%; <0.01).
Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients.
https://www.clinicaltrials.gov. Unique Identifier: NCT00292032.
不明原因的心脏骤停可能是由遗传性心律失常综合征引起的。基因检测在没有明确临床表型的心脏骤停幸存者中的作用尚不清楚。
CASPER（射血分数保留的心脏骤停幸存者注册研究）是一个大型的心脏骤停幸存者注册研究，其初始评估显示冠状动脉、左心室功能和静息心电图正常。在2006年至2015年期间纳入CASPER的375名心脏骤停幸存者中，174人接受了基因检测。患者被分为表型阳性（n = 72）或表型阴性（n = 102）。基因检测由治疗医生根据当代指南和可及性自行决定进行。研究人员根据现代标准对原始实验室报告中识别出的所有基因变异进行了重新评估。在29名（17%）患者中鉴定出致病变异（60%与离子通道病相关基因，40%与心肌病相关基因），在32名（18%）患者中鉴定出70个意义未明的变异。既往晕厥（比值比，4.0；95%置信区间，1.6 - 9.7）和猝死家族史（比值比，3.2；95%置信区间，1.1 - 9.4）与致病变异的存在独立相关。在表型阴性患者中，广泛的多表型基因检测导致更高的检出率（21%对8%；P = 0.04），但与更多意义未明的变异相关（55%对5%；P < 0.01）。
基因检测在相当比例的不明原因心脏骤停幸存者中识别出致病变异。既往晕厥和猝死家族史是基因检测阳性的预测因素。心律失常和心肌病相关基因均有涉及。广泛的多表型检测在表型阴性患者中显示出最高频率的致病变异。
