LMNA Mutations and Right Heart Failure in Patients With Cardiomyopathy and With Left Ventricular Assist Devices
LMNA Mutations and Right Heart Failure in Patients With Cardiomyopathy and With Left Ventricular Assist Devices
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使用左心室辅助装置的心肌病患者的 LMNA 突变和右心力衰竭
DOI：
10.1016/j.cardfail.2023.01.011
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发表时间：
2023
影响因子：
6
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
YAMADA TAKANOBU;NOMURA SEITARO;AMIYA EISUKE;et al
扩张型心肌病（DCM）是需要左心室辅助装置（LVAD）或心脏移植的晚期心力衰竭的主要原因。虽然LVAD的植入改善了终末器官功能障碍并提高了运动耐量，但LVAD植入后的右心衰竭（RHF）仍然是一个未解决的主要问题。1据报道，LVAD植入后晚期RHF的发生率为8 - 11%，预后不良。2因此，预测LVAD术后晚期RHF的发生具有重要意义。我们假设遗传因素参与了LVAD植入后晚期RHF的发展，并检查了导致严重表型DCM的核纤层蛋白A/C（LMNA）突变3是否与LVAD植入后晚期RHF和预后不良相关。在2012年至2019年在东京大学医院接受LVAD植入作为移植桥梁的DCM患者中，我们招募了92名接受基因分析的个体。根据伦理委员会批准的方案，获得所有患者的书面知情同意书。使用一个全面的心肌病基因面板，针对超过100个心肌病相关基因的外显子和剪接区，我们进行了基因组分析91例DCM患者。剩余的患者通过桑格测序被定义为LMNA基因中具有致病性突变。根据美国医学遗传学学会（ACMG）指南评估变异体的致病性。4
Dilated cardiomyopathy (DCM) is a major cause of advanced heart failure requiring a left ventricular assist device (LVAD) or heart transplantation. Although implantation of an LVAD ameliorates end-organ dysfunction and improves exercise tolerance, right heart failure (RHF) after LVAD implantation remains a major unsolved problem. 1 The incidence of RHF in the late phase after LVAD implantation has been reported to be 8-11% and associated with a poor prognosis. 2 Therefore, it is important to predict the development of late RHF after LVAD implantation. We hypothesized that genetic factors are involved in the development of late RHF after LVAD implantation and examined whether Lamin A/C (LMNA) mutations, which cause DCM with a severe phenotype, 3 are associated with late RHF and poor prognosis after LVAD implantation.Among DCM patients who received LVAD implantation as a bridge to transplantation at the University of Tokyo Hospital from 2012 to 2019, we enrolled 92 individuals who underwent genetic analysis. Written informed consent was obtained from all patients by the protocol approved by the ethics committee. Using a comprehensive cardiomyopathy gene panel that targeted the exons and splicing regions of over 100 cardiomyopathy-related genes, we conducted a genomic analysis of 91 patients with DCM. The remaining patient was defined as having pathogenic mutations in the LMNA gene by Sanger sequencing. The pathogenicity of variants was evaluated according to American College of Medical Genetics (ACMG) guidelines. 4