Kutyifa Valentina, Daimee Usama A, McNitt Scott, Polonsky Bronislava, Lowenstein Charles, Cutter Kris, Lopes Coeli, Zareba Wojciech, Moss Arthur J
Heart Research Follow-up Program in the Cardiology Unit, University of Rochester Medical Center, Rochester, NY, USA.
Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Ann Noninvasive Electrocardiol. 2018 May;23(3):e12537. doi: 10.1111/anec.12537. Epub 2018 Mar 5.
A comprehensive report on the clinical course of the three major genotypes of the long QT syndrome (LQTS) in a large U.S. patient cohort is lacking.
Our study consisted of 1,923 U.S. subjects from the Rochester-based LQTS Registry with genotype-positive LQT1 (n = 879), LQT2 (n = 807), and LQT3 (n = 237). We evaluated the risk of a first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death, whichever occurred first) from birth through age 50 years. Cox proportional hazards regression models incorporating clinical covariates were used to assess genotype-specific risk of cardiac events.
For all three genotypes, the cumulative probability of a first cardiac event increased most markedly during adolescence. Multivariate analysis identified proband status and QTc > 500 ms as predictors of cardiac events in all three genotypes, and males <14 years and females >14 years as predictors of cardiac events in LQT1 and LQT2 only. Beta-blockers significantly reduced the risk of cardiac events in LQT1 (HR: 0.49, p = .002) and LQT2 patients (HR: 0.48, p = .001). A trend toward beta-blocker benefit in reducing cardiac events was found in LQT3 females (HR: 0.32, p = .078), but not in LQT3 males (HR: 1.37, p = .611).
Risk factors and outcomes in LQTS patients varied by genotype. In all three genotypes, proband status and prolonged QTc were risk factors for cardiac events. Younger males and older females experienced increased risk in LQT1 and LQT2 only. Beta-blockers were most effective in reducing cardiac events in LQT1 and LQT2, with a potential benefit in LQT3 females.
目前尚缺乏关于美国一大群长QT综合征（LQTS）患者中三种主要基因型临床病程的综合报告。
我们的研究纳入了来自罗切斯特LQTS注册中心的1923名美国受试者，其中基因型阳性的LQT1患者879例、LQT2患者807例、LQT3患者237例。我们评估了从出生到50岁首次发生心脏事件（晕厥、心脏骤停未遂或心源性猝死，以首次发生者为准）的风险。采用纳入临床协变量的Cox比例风险回归模型评估心脏事件的基因型特异性风险。
对于所有三种基因型，首次发生心脏事件的累积概率在青春期增加最为显著。多变量分析确定，先证者状态和QTc>500 ms是所有三种基因型心脏事件的预测因素，仅在LQT1和LQT2中，年龄<14岁的男性和年龄>14岁的女性是心脏事件的预测因素。β受体阻滞剂显著降低了LQT1患者（HR：0.49，p = 0.002）和LQT2患者（HR：0.48，p = 0.001）发生心脏事件的风险。在LQT3女性中发现了β受体阻滞剂在降低心脏事件方面的有益趋势（HR：0.32，p = 0.078），但在LQT3男性中未发现（HR：1.37，p = 0.611）。
LQTS患者的危险因素和预后因基因型而异。在所有三种基因型中，先证者状态和QTc延长是心脏事件的危险因素。仅在LQT1和LQT2中，年轻男性和老年女性发生心脏事件的风险增加。β受体阻滞剂在降低LQT1和LQT2患者心脏事件方面最为有效，对LQT3女性可能有益。
