Amsterdam UMC, University of Amsterdam, Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (P.J.P., K.V.V.L., M.T., C.v.d.W., A.A.M.W.).
Department of Pediatric Cardiology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, The Netherlands (P.J.P., S.-A.B.C., N.A.B.).
Circulation. 2022 Feb;145(5):333-344. doi: 10.1161/CIRCULATIONAHA.121.056018. Epub 2021 Dec 7.
Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT.
From 2 international registries of patients with CPVT, variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and age at start of β-blocker therapy <18 years), treated with a β-blocker were included. Cox regression analyses with time-dependent covariates for β-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope.
We included 329 patients (median age at diagnosis, 12 [interquartile range, 7-15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8-12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective β-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a β1-selective β-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial β-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for β1-selective compared with nonselective β-blockers (HR, 2.04 [95% CI, 1.31-3.17]; and HR, 1.99 [95% CI, 1.20-3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44-4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47-7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08-4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30-5.55]).
β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT.
有症状的儿茶酚胺多形性室性心动过速（CPVT）患儿存在心律失常事件复发的风险。β受体阻滞剂可降低这种风险，但缺乏比较大样本量的 CPVT 患儿使用不同β受体阻滞剂的研究。我们旨在评估在一个大型 CPVT 有症状患儿队列中，心律失常事件的风险与β受体阻滞剂类型之间的关系。
从 CPVT 的两个国际注册中心中，纳入携带变异的有症状患儿（定义为在开始使用β受体阻滞剂之前发生晕厥或心搏骤停，且开始β受体阻滞剂治疗的年龄＜18 岁），并接受β受体阻滞剂治疗。使用时间依赖性协变量的 Cox 回归分析来评估β受体阻滞剂和潜在混杂因素的危险比（HR）。主要结局是心源性猝死、心搏骤停、适当的植入式心脏复律除颤器电击或晕厥的首次发生。次要结局是除晕厥外任何主要结局的首次发生。
我们纳入了 329 名患者（诊断时的中位年龄为 12 岁[四分位间距 7-15 岁]，35%为女性）。99 名（30.1%）患者发生了主要结局，74 名（22.5%）患者在中位随访 6.7 年（四分位间距 2.8-12.5 年）期间发生了次要结局。216 名（66.0%）患者使用了非选择性β受体阻滞剂（主要是纳多洛尔[n=140]或普萘洛尔[n=70]），111 名（33.7%）患者使用了β1-选择性β受体阻滞剂（主要是阿替洛尔[n=51]、美托洛尔[n=33]或比索洛尔[n=19]）作为初始β受体阻滞剂。基线特征无差异。β1-选择性β受体阻滞剂的主要和次要结局的 HR 均高于非选择性β受体阻滞剂（HR 分别为 2.04[95%CI，1.31-3.17]和 1.99[95%CI，1.20-3.30]）。分别评估时，阿替洛尔的主要结局 HR 更高（HR 为 2.68[95%CI，1.44-4.99]），比索洛尔（HR 为 3.24[95%CI，1.47-7.18]）和美托洛尔（HR 为 2.18[95%CI，1.08-4.40]）与纳多洛尔相比，但与普萘洛尔无差异。次要结局的 HR 仅在阿替洛尔中高于纳多洛尔（HR 为 2.68[95%CI，1.30-5.55]）。
β1-选择性β受体阻滞剂与 CPVT 有症状患儿心律失常事件的风险显著高于非选择性β受体阻滞剂，特别是纳多洛尔。纳多洛尔或如果纳多洛尔不可用，则应首选普萘洛尔作为治疗 CPVT 有症状患儿的β受体阻滞剂。
