Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.
Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.
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DOI：
10.1212/wnl.0000000000010794
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发表时间：
2020-11-24
期刊：
影响因子：
9.9
通讯作者：
Sisodiya SM
中科院分区：
文献类型：
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作者：
Balestrini S;Mikati MA;Álvarez-García-Rovés R;Carboni M;Hunanyan AS;Kherallah B;McLean M;Prange L;De Grandis E;Gagliardi A;Pisciotta L;Stagnaro M;Veneselli E;Campistol J;Fons C;Pias-Peleteiro L;Brashear A;Miller C;Samões R;Brankovic V;Padiath QS;Potic A;Pilch J;Vezyroglou A;Bye AME;Davis AM;Ryan MM;Semsarian C;Hollingsworth G;Scheffer IE;Granata T;Nardocci N;Ragona F;Arzimanoglou A;Panagiotakaki E;Carrilho I;Zucca C;Novy J;Dzieżyc K;Parowicz M;Mazurkiewicz-Bełdzińska M;Weckhuysen S;Pons R;Groppa S;Sinden DS;Pitt GS;Tinker A;Ashworth M;Michalak Z;Thom M;Cross JH;Vavassori R;Kaski JP;Sisodiya SM
明确ATP 1A 3相关综合征中心脏异常的风险和后果。纳入了符合临床诊断标准的患者，包括速发型肌张力障碍-帕金森综合征（RDP）、儿童期交替性偏瘫（AHC）、小脑共济失调、反射消失、高脚、视神经萎缩和感觉神经性听力损失（CAPOS），并进行了ATP 1A 3遗传分析和至少1次心脏评估。我们评估了Atp 1a 3基因敲入小鼠（Mashl+/−）的心脏表型，以确定心脏病相关心脏死亡事件的顺序。纳入了98例AHC患者、9例RDP患者和3例CAPOS患者（63例女性，平均年龄17岁）。87例AHC患者中有52例（60%）发现静息心电图异常，3例CAPOS患者中有2例（67%）发现静息心电图异常，9例RDP患者中有6例（67%）发现静息心电图异常。18例AHC中10例动态心电图改变。65例AHC和RDP患者中24例（37%）首次霍尔特ECG异常，伴复极或传导异常。超声心动图正常。98例AHC患者中有3例（约3%）需要心脏介入治疗。在小鼠模型中，静息ECG显示心内传导延迟;在诱导癫痫发作期间，心脏传导阻滞或完全窦性停搏导致死亡。我们发现，在所有ATP 1A 3相关综合征中，ECG动态异常的患病率增加，危及生命的心律异常的风险与已确定的心脏通道病相当（1.3%）。在小鼠Atp 1a 3相关疾病中，由于传导异常导致的心脏性猝死是一种与心脏病相关的结局。ATP 1A 3相关综合征是心脏疾病和神经系统疾病。我们提供了指南，以识别可能从植入起搏器或植入式心律转复除颤器中获益的心源性猝死风险较高的患者。
To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/−) to determine the sequence of events in seizure-related cardiac death. Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.