Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease
Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease
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评估扩张型心肌病的遗传和表型特征与冠状动脉疾病患者的预后之间的关联
DOI：
10.1002/ejhf.3033
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发表时间：
2023
影响因子：
18.2
通讯作者：
Jones R
中科院分区：
文献类型：
--
作者：
Jones R
目的探讨冠心病患者扩张型心肌病（DCM）的遗传和心血管磁共振（CMR）特征的相关性。首先，对招募到英国生物库（UKB）的CAD患者进行评估。其次，招募了转诊至三级中心接受晚期钆增强（LGE）-CMR评价的CAD患者（伦敦队列）;患者接受基因测序，作为研究方案和长期随访的一部分。从UKB招募的31154名CAD患者中，DCM基因中罕见的致病性变异与死亡或主要不良心脏事件的风险增加相关（风险比1.57，95%置信区间[CI] 1.22- 2.01，p < 0.001）。在UKB CMR子研究纳入的1619名CAD患者中，与基因型阴性个体相比，DCM相关基因中具有罕见变异的参与者的左心室射血分数（LVEF）较低（平均47 ± 10% vs. 57 ± 8%，p < 0.001）。在伦敦队列的453例患者中，63例（14%）在CMR上具有非梗死模式LGE（NI‐LGE）。NI-LGE患者的LVEF（平均值38 ± 18% vs. 48 ± 16%，p < 0.001）低于非NI-LGE患者，两组间DCM相关基因中罕见蛋白改变变体的负担无显著差异（9.5% vs. 6.7%，比值比1.5，95% CI 0.4- 4.3，p = 0.4）。NI-LGE与不良临床结局无关。结论DCM相关基因中罕见的致病变异影响稳定型CAD的左心室重构和结局。NI-LGE与不良重塑相关，但不是结果的独立预测因素，在我们的研究中没有罕见的遗传基础。
AimsTo examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD).Methods and resultsThis study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)‐CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long‐term follow‐up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22–2.01,p< 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM‐associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%,p< 0.001). Of 453 patients in the London cohort, 63 (14%) had non‐infarct pattern LGE (NI‐LGE) on CMR. Patients with NI‐LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%,p< 0.001) compared to patients without NI‐LGE, with no significant difference in the burden of rare protein altering variants in DCM‐associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4–4.3,p= 0.4). NI‐LGE was not independently associated with adverse clinical outcomes.ConclusionRare pathogenic variants in DCM‐associated genes impact left ventricular remodelling and outcomes in stable CAD. NI‐LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.