关于不同遗传背景与非缺血性扩张型心肌病 (DCM) 相关影响的证据仍然相互矛盾。本研究试图综合有关 DCM 中不同基因组的长期结果的可用数据。系统地筛选电子数据库，以确定报告预先指定基因组的预后数据的研究。这些包括致病性/可能致病性 (P/LP) 变异、截短肌联蛋白变异 (TTNtv)、核纤层蛋白 A/C 变异 (LMNA) 和桥粒蛋白。结果分为复合不良事件（CAE）、恶性室性心律失常事件（MVAE）和心力衰竭事件（HFE）。荟萃分析共纳入 26 项研究 (n = 7255)，对 6791 名基因分型 DCM 患者进行了分析。具有 P/LP 变异的患者发生 CAE（比值比 [OR] 2.10，95% 置信区间 [CI] 1.67-2.65）、MVAE（OR 1.86，95% CI 1.52-2.26）和 HFE（OR 2.01）的风险较高，95% CI 1.08-3.73）高于基因型阴性患者。 TTNtv 的存在与 CAE 的较高风险相关（OR 1.78，95% CI 1.20-2.63），但与 MVAE 或 HFE 无关。与非 LMNA 和非桥粒组相比，LMNA 和桥粒组的 CAE、MVAE 和 HFE 风险分别更高。当间接比较基因时，就所有复合结果而言，LMNA 的存在比 TTNtv 产生更有害的影响，但 LMNA 和桥粒基因之间没有发现显着差异。与 TTNtv 相比，桥粒基因具有更高的 MVAE 风险。与 DCM 相关的不同遗传底物导致不同的自然史。应常规利用基因检测来完善 DCM 的风险分层并为治疗策略提供信息。© 2024 作者。约翰·威利出版的《欧洲心力衰竭杂志》

Evidence on the relative impact of diverse genetic backgrounds associated with non-ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long-term outcomes of different gene groups in DCM.Electronic databases were systematically screened to identify studies reporting prognostic data on pre-specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta-analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67-2.65), MVAEs (OR 1.86, 95% CI 1.52-2.26), and HFEs (OR 2.01, 95% CI 1.08-3.73) than genotype-negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20-2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non-LMNA and non-desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv.Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM.© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.