长 QT 综合征患者遗传基础、QTc 持续时间与心律失常风险之间的相互作用。

Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.

机构信息

Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy.

出版信息

J Am Coll Cardiol. 2018 Apr 17;71(15):1663-1671. doi: 10.1016/j.jacc.2018.01.078.

DOI:10.1016/j.jacc.2018.01.078

PMID:29650123

Abstract

BACKGROUND

Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs).

OBJECTIVES

This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS.

METHODS

Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers.

RESULTS

The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03).

CONCLUSIONS

The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS.

摘要

背景

长 QT 综合征（LQTS）是一种常见的遗传性心律失常疾病，通常继发于 KCNQ1、KCNH2 和 SCN5A 基因突变。该疾病的特征是心室复极延长（QTc 间期），使患者易发生危及生命的心律失常事件（LAEs）。

目的

本研究旨在制定一个基于证据的风险分层方案，以个体化量化 LQTS 患者的心律失常风险。

方法

分析了 1710 例 LQTS 患者的数据，这些患者的中位随访时间为 7.1 年（四分位距 [IQR]：2.7 至 13.4 年），以根据 QTc 持续时间和基因型估计 5 年 LAEs 风险，并评估β受体阻滞剂的抗心律失常疗效。

结果

通过比较线性和三次样条模型，研究了 QTc 持续时间与事件风险之间的关系，线性模型提供了最佳拟合。然后，在多变量 Cox 模型中，将 QTc 和基因型作为独立因素，计算患者停药时的 5 年 LAEs 风险。对于所有基因型，每增加 10ms 的 QTc 持续时间，LAEs 的风险增加 15%。基因型间比较显示，与 LQT1 患者相比，任何 QTc 持续时间下 LQT2 和 LQT3 患者的风险增加 130%和 157%。β受体阻滞剂反应分析显示，与无治疗相比，仅纳多洛尔显著降低了所有基因型的心律失常风险（危险比：0.38；95%置信区间：0.15 至 0.93；p=0.03）。