Department of Cardiology, Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands.
Circ Arrhythm Electrophysiol. 2012 Aug 1;5(4):748-56. doi: 10.1161/CIRCEP.112.970517. Epub 2012 Jul 10.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited.
One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5-11.5; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3-19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4-20.9 years).
Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.
儿茶酚胺多形性室性心动过速（CPVT）是一种遗传性心律失常综合征，与大多数患者的心脏兰尼碱受体基因（Ryr2）突变有关。以前对 CPVT 患者的研究主要涉及先证者，因此目前对携带 Ryr2 突变的亲属的疾病外显率、表达、基因型-表型相关性以及心律失常事件发生率的了解是有限的。
通过对先证者中引起 CPVT 的 Ryr2 突变进行级联筛查，从 15 个家族中鉴定出 116 名携带 Ryr2 突变的亲属进行临床特征分析，其中 61 名亲属来自 1 个家族。在 108 名未服用抗心律失常药物的亲属中，有 54 名（50%）在首次心脏检查时出现 CPVT 表型，其中 27 名（25%）有非持续性室性心动过速。携带 Ryr2 突变的 C 端通道形成域的亲属发生非持续性室性心动过速的几率增加（比值比，4.1；95%置信区间，1.5-11.5；P=0.007，与 N 端域相比）与 N 端域。19%的亲属出现窦性心动过缓，而其他 16%的亲属出现室上性心律失常。98 名（治疗最积极）亲属（84%）接受中位数为 4.7 年（范围，0.3-19.0 年）的随访。在随访期间，2 名无症状亲属出现运动诱发的晕厥。1 名亲属未接受治疗，另 1 名亲属不遵医嘱。在 6.7 年的随访期间（范围，1.4-20.9 年），116 名亲属中没有 1 人死于 CPVT。
携带 Ryr2 突变的亲属表现出明显的表型多样性。绝大多数亲属没有出现室上性疾病表现。突变位置可能与表型严重程度有关。随访期间心律失常事件发生率较低。
