Background

Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist.

Objective

The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events.

Methods

A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10–18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups.

Results

A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3–11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10- and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on β-blocker or flecainide alone vs 10% (5/48) in patients on β-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001).

Conclusion

Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors.

中文翻译：

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评估症状发作时的年龄、先证者状态和性别作为儿茶酚胺能多形性室性心动过速疾病严重程度的预测因子

背景

儿茶酚胺能多形性室性心动过速 (CPVT) 的儿童有猝死的风险，并且不存在风险分层工具。

客观的

本研究的目的是确定先证者状态、症状发作时的年龄和/或性别是否是心脏事件的独立预测因素。

方法

一个多中心、双向的儿科 CPVT 患者队列按性别、先证者状态和症状发作时的年龄进行分类（D1：生命的第一个十年[症状发作 <10 岁]或 D2：生命的第二个十年[症状发作 10-18年，包括]）。比较了各组之间的人口统计学、治疗、遗传学和结果。

结果

共有 133 名患者被纳入并分层为 58 名 D1 和 75 名 D2 患者（68 名女性和 65 名男性；106 名先证者和 27 名亲属）。RYR2变体对热点的定位因先证者状态和症状发作时的年龄而异。心脏事件发生率为 33% (n = 44/133)，包括 3% (n = 4/133) 的死亡率，在症状出现后的中位 6 年（四分位距 3-11）内。先证者状态，而不是症状出现时的年龄或性别，是首次心脏事件发生时间的独立预测因子（P= .008; 风险比 = 4.4）。先证者的 5 年、10 年和 15 年无事件生存率分别为 77%、56% 和 46%，亲属分别为 96%、91% 和 86%。单独使用 β 受体阻滞剂或氟卡尼的患者诊断后的事件风险为 48% (32/67)，而使用 β 受体阻滞剂加氟卡尼和/或左心交感神经去神经支配的患者为 10% (5/48) ( P  <.001) .

结论

先证者状态，但不是症状发作时的年龄或男性，独立预测心脏事件的早期发作。更大的样本量将使对其他风险因素的全面调查成为可能。