Abstract：
BACKGROUND: Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS.
METHODS: We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD).
RESULTS: During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups.
CONCLUSIONS: The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.
METHODS: We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD).
RESULTS: During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups.
CONCLUSIONS: The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.
摘要：
背景：尽管先前的研究表明，单基线12导联心电图（ECG）的QTc>500ms与长QT综合征（LQTS）中心律失常事件的风险显着增加有关，对持续QT间期延长的风险知之甚少。我们试图在接受LQTS治疗的儿科患者中确定QTc持续及其对突破性心脏事件（BCEs）的预后影响。
方法：我们对433例LQTS患者进行了回顾性分析，风险分层，并在1999年至2019年期间接受积极的基于指南的LQTS治疗。BCE被定义为心律失常性晕厥/癫痫发作，心脏骤停(SCA),适当的VF终止ICD电击,和心源性猝死（SCD）。
结果：在5.5年的中位随访期间（四分位距[IQR]=3-9），32例(7%)患者总共经历了129例BCEs。520ms的最大QTc阈值和490ms的中值QTc阈值被确定为BCE的强预测因子。控制年龄的里程碑分析，性别,基因型，和症状状态证明的模型同时利用中位数QTc和最大QTc显示出最高的判别值（c统计量=0.93-0.95）。与中等风险（93％-97％）和低风险（98％-99％）组的患者相比，高风险组（中位QTc>490ms和最大QTc>520ms）的患者无BCE生存率（70％-81％）明显较低。
结论：接受LQTS治疗的患者发生BCE的风险不仅根据其最大QTc增加，而且他们的中位数QTc（QTc延长的持续性）。在进行指南指导的药物治疗时，连续12导联心电图的最大QTc>520ms且中位QTc>490ms的患者发生BCE的风险最高。
方法：我们对433例LQTS患者进行了回顾性分析，风险分层，并在1999年至2019年期间接受积极的基于指南的LQTS治疗。BCE被定义为心律失常性晕厥/癫痫发作，心脏骤停(SCA),适当的VF终止ICD电击,和心源性猝死（SCD）。
结果：在5.5年的中位随访期间（四分位距[IQR]=3-9），32例(7%)患者总共经历了129例BCEs。520ms的最大QTc阈值和490ms的中值QTc阈值被确定为BCE的强预测因子。控制年龄的里程碑分析，性别,基因型，和症状状态证明的模型同时利用中位数QTc和最大QTc显示出最高的判别值（c统计量=0.93-0.95）。与中等风险（93％-97％）和低风险（98％-99％）组的患者相比，高风险组（中位QTc>490ms和最大QTc>520ms）的患者无BCE生存率（70％-81％）明显较低。
结论：接受LQTS治疗的患者发生BCE的风险不仅根据其最大QTc增加，而且他们的中位数QTc（QTc延长的持续性）。在进行指南指导的药物治疗时，连续12导联心电图的最大QTc>520ms且中位QTc>490ms的患者发生BCE的风险最高。
