Tuijnenburg Fenna, Proost Virginnio M, Thollet Aurélie, Barc Julien, Groffen Alexander J A, Veerman Christiaan C, van der Crabben Saskia N, van der Pas Vincent R, Kyndt Florence, Jurgens Sean J, Tanck Michael W T, Postema Pieter G, Peter van Tintelen J, Bezzina Connie R, Probst Vincent, Wilde Arthur A M, Gourraud Jean-Baptiste, Amin Ahmad S
Department of Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Heart Rhythm. 2025 May;22(5):1321-1329. doi: 10.1016/j.hrthm.2024.10.057. Epub 2024 Nov 2.
The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown.
This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events.
Probands and family members with (likely) pathogenic SCN5A loss-of-function variants were retrospectively included. Clinical and electrocardiographic data at baseline and last follow-up were collected. Patients with a history of cardiac arrest, sustained ventricular tachycardia, symptomatic or documented atrial tachy- or bradyarrhythmia, or arrhythmogenic syncope were categorized as symptomatic. Arrhythmic events at follow-up were defined as sudden death, aborted cardiac arrest, documented ventricular fibrillation, and/or sustained ventricular tachycardia.
We included 615 patients (349 men, 242 probands, 157 with a spontaneous type 1 Brugada electrocardiogram, and 111 symptomatic at baseline). During a median follow-up of 9.5 (Q1,Q3 5.0-14.3) years, arrhythmic events occurred in 41 patients (6.7%), equating an overall event rate of 0.7%/y: 2.0%/y in symptomatic and 0.3%/y in asymptomatic patients. In the overall study population, symptoms at baseline, male sex, and QRS prolongation were identified as independent predictors of arrhythmic events. In asymptomatic patients, male sex and QRS prolongation were also identified as predictors. Asymptomatic women with QRS interval < 100 ms did not experience arrhythmic events at follow-up.
Key predictors of arrhythmic risk in patients with an SCN5A loss-of-function variant, regardless of a Brugada syndrome diagnosis, are symptoms at baseline, male sex, and prolonged QRS interval. Our findings may enable more tailored management strategies in patients with an SCN5A loss-of-function variant based on their individual risk profiles.
心脏钠通道基因SCN5A功能缺失变异患者的长期预后尚不清楚。
本研究旨在评估SCN5A功能缺失变异患者的长期心律失常风险，以确定心律失常事件的预测因素。
回顾性纳入携带（可能）致病性SCN5A功能缺失变异的先证者及其家庭成员。收集基线和末次随访时的临床及心电图数据。有心脏骤停、持续性室性心动过速、有症状或记录到的房性心动过速或缓慢性心律失常、或致心律失常性晕厥病史的患者被归类为有症状患者。随访时的心律失常事件定义为猝死、心脏骤停复苏、记录到的心室颤动和/或持续性室性心动过速。
我们纳入了615例患者（349例男性，242例先证者，157例有自发性1型Brugada心电图表现，111例在基线时有症状）。在中位随访9.5（四分位间距5.0 - 14.3）年期间，41例患者（6.7%）发生心律失常事件，总体事件发生率为0.7%/年：有症状患者为2.0%/年，无症状患者为0.3%/年。在整个研究人群中，基线时的症状、男性性别和QRS波增宽被确定为心律失常事件的独立预测因素。在无症状患者中，男性性别和QRS波增宽也被确定为预测因素。QRS间期<100 ms的无症状女性在随访期间未发生心律失常事件。
无论是否诊断为Brugada综合征，SCN5A功能缺失变异患者心律失常风险的关键预测因素是基线时的症状、男性性别和QRS间期延长。我们的研究结果可能有助于根据SCN5A功能缺失变异患者的个体风险特征制定更具针对性的管理策略。
