BACKGROUND Long QT syndrome (LQTS) is a leading cause of sudden cardiac death in early life and has been implicated in ≈10% of sudden infant deaths and unexplained stillbirths. The purpose of our study was to use fetal magnetocardiography to characterize the electrophysiology and rhythm phenotypes of fetuses with de novo and inherited LQTS variants and identify risk factors for sudden death before birth. METHODS We reviewed the fetal magnetocardiography database from the University of Wisconsin Biomagnetism Laboratory for fetuses with confirmed LQTS. We assessed waveform intervals, heart rate, and rhythm, including the signature LQTS rhythms: functional 2° atrioventricular block, T-wave alternans, and torsade de pointes (TdP). RESULTS Thirty-nine fetuses had pathogenic variants in LQTS genes: 27 carried the family variant, 11 had de novo variants, and 1 was indeterminate. De novo variants, especially de novo SCN5A variants, were strongly associated with a severe rhythm phenotype and perinatal death: 9 (82%) showed signature LQTS rhythms, 6 (55%) showed TdP, 5 (45%) were stillborn, and 1 (9%) died in infancy. Those that died exhibited novel fetal rhythms, including atrioventricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle length TdP, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with TdP and perinatal death. Fetuses with familial variants showed a lower incidence of signature LQTS rhythm (6/27=22%), including TdP (3/27=11%). All were live born. CONCLUSIONS The malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. Their ability to manifest rhythms not known to be associated with LQTS increases the difficulty of echocardiographic diagnosis and decreases the likelihood that a resultant fetal loss is attributed to LQTS. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03047161.

中文翻译：

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患有De Novo Long QT综合征的胎儿中复杂而新颖的心律失常优先于死胎。

背景技术长QT综合征（LQTS）是生命早期猝死的主要原因，并已导致约10％的婴儿猝死和无法解释的死产。我们研究的目的是使用胎儿心动图来表征从头和遗传LQTS变异的胎儿的电生理和节律表型，并确定出生前猝死的危险因素。方法我们回顾了威斯康星大学生物磁实验室的胎儿心电图数据库，以确认LQTS的胎儿。我们评估了波形间隔，心率和节律，包括标志性的LQTS节律：功能性2°房室传导阻滞，T波交响神经和尖端扭转型室速（TdP）。结果39例胎儿的LQTS基因具有致病性变异：27具家庭变异，11个具有从头开始的变体，而1个不确定。从头变异，特别是从头SCN5A变异，与严重的节律表型和围产期死亡密切相关：9（82％）表现出特征性LQTS节奏，6（55％）表现出TdP，5（45％）死于，1 （9％）在婴儿期死亡。死亡者表现出新颖的胎儿节律，包括传导比为3：1的房室传导阻滞，2：1的房室传导阻滞中的QRS交替，长周期长度TdP和缓慢的单形性室性心动过速。室性早搏也与TdP和围产期死亡密切相关。具有家族变异的胎儿表现出较低的特征性LQTS节律发生率（6/27 = 22％），包括TdP（3/27 = 11％）。所有人都活着出生。结论从头LQTS变异的恶性程度很高，表明这些突变是死产的重要原因。它们表现出与LQTS不相关的节律的能力增加了超声心动图诊断的难度，并降低了因LQTS导致胎儿流产的可能性。注册：URL：http：//www.clinicaltrials.gov。唯一标识符：NCT03047161。