目的：左室心肌致密化不全是一种罕见的心肌病，其特征为心肌小梁突出及小梁间隐窝深陷。目前其发病机制尚不明确，既往研究认为其可能与遗传基因突变或后天心肌劳损代偿相关，但尚无血清标志物及致病分子通路相关研究。左室心肌致密化不全的预后及预后相关影响因素的研究也尚不明确，国内缺乏随访期长的临床研究。本研究旨在通过回顾性队列研究，总结左室心肌致密化不全的临床特征、预后情况，探索预后相关影响因素；并利用蛋白质组学技术，寻找左室心肌致密化不全潜在的血清标志物及分子致病通路。方法：本研究为一项单中心、回顾性队列研究，纳入了2008年1月1日至2020年12月30日在北京协和医院心内科住院或门诊就诊的患者。利用病历系统获取患者的个人基本信息、临床病史、实验室检验及影像学检查结果。本研究的主要终点事件为心血管原因死亡，次要终点事件包括再次住院。采用Kaplan-Meier进行生存分析，利用cox风险回归模型分析进行单因素及多因素分析以探究预后相关危险因素。收集患者及健康对照血清进行蛋白质组学研究，利用生信分析寻找差异表达蛋白，并使用GO、KEGG及结构域富集方法探寻潜在分子通路。结果：本研究共纳入70名患者，平均确诊年龄为46.07岁，男性占62.9%。在平均69个月的随访时间中，死亡率为21.4%。单因素Cox分析显示男性、吸烟、BMI、体重减轻、NYHA分级、日常生活评分、炎症指标、左室射血分数、左心室血栓、及右心增大均与预后相关。多因素分析显示BMI、右心室增大是左室心肌致密化不全的预后相关独立危险因素。对左室心肌致密化不全患者微血管的研究并未发现患者存在微循环病变。蛋白质组学分析发现，左室心肌致密化不全患者与健康对照的血清差异蛋白主要为免疫球蛋白、纤连蛋白、成纤维细胞生长因子受体1（FGFR1）及血管内皮生长因子受体3（VEGFR3）。涉及的分子通路主要为蛋白磷酸化通路、胞内蛋白修饰通路及转移酶通路。这些通路多为感染及自身免疫病相关通路。结论：本研究汇总的左室心肌致密化不全队列与既往文献报道的左室心肌致密化不全临床表现及影像学特征相似。与预后相关的因素为：男性、吸烟、BMI、体重减轻、NYHA分级、日常生活评分、炎症指标、左室射血分数、左心室血栓及右心增大。其中，BMI与右心室增大是左室心肌致密化不全患者的预后独立危险因素。蛋白质组学的研究显示炎症、免疫及纤维化相关通路可能参与到左室心肌致密化不全的发生发展过程中。

Objective: Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by prominent trabeculae, intratrabecular recesses, and myocardium with both compacted and non-compacted layers. At present, its pathogenesis is still unclear. Previous studies suggested that it may be related to gene mutation or compensation of myocardium to systolic dysfunction or volume overload, but there lacks research on serum markers and pathogenic molecular pathways. Few studies focused on the prognosis of left ventricular noncompaction, and factors related to prognosis of left ventricular noncompaction are still unclear. Also, there is a lack of clinical studies with long-term follow-up in China. The purpose of this study is to summarize the clinical features and explore prognostic related factors of left ventricular noncompaction through a retrospective cohort study, Proteomics techniques were also used to find potential serum markers and molecular pathogenic pathways of left ventricular noncompaction. Methods: This study was a single center, retrospective cohort study, which included inpatients or outpatients in the Department of Cardiology of Peking Union Medical College Hospital from January 1, 2008 to December 30, 2020. Baseline information, clinical history, laboratory test and imaging examination results of patients were obtained from medical record system. The primary endpoint of this study was cardiovascular death. The secondary endpoint was readmission. Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for univariate and multivariate analyses to explore the prognostic risk factors. Serum samples of patients and healthy controls were collected for proteomic analysis. The differentially expressed proteins were identified by bioinformatics analysis, and the potential molecular pathways were explored by GO, KEGG and domain enrichment methods. Results: A total of 70 patients were enrolled in this study. The average age at diagnosis was 46.07 years. Males accounted for 62.9%. During an average follow-up of 69 months, the mortality rate was 21.4%. Univariate Cox regression analysis showed that male, smoking, BMI, weight loss, NYHA class, Barthel index, inflammation, left ventricular ejection fraction (LVEF), left ventricular thrombosis, and right ventricular enlargement were associated with prognosis. Multivariate analysis showed that BMI and right ventricular enlargement were independent prognostic factors for left ventricular noncompaction. The study of microvessel in patients with left ventricular noncompaction did not find microcirculation lesions. Proteomic analysis showed that the expression of immunoglobulin, fibronectin, fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 3 (VEGFR3) were up-regulated in left ventricular noncompaction patients. The main molecular pathways involved are protein phosphorylation pathway, intracellular protein modification pathway and transferase pathway. Most of these pathways are related to infection and autoimmune diseases. Conclusion: The clinical manifestations and imaging features of left ventricular noncompaction in our cohort are similar to those reported in previous literatures. Male, smoking, BMI, weight loss, NYHA grade, daily life score, inflammation index, left ventricular ejection fraction (LVEF), left ventricular thrombosis and right ventricular enlargement were prognostic factors for left ventricular noncompaction. Among them, BMI and right ventricular enlargement were independent factors for survival Proteomic studies show that inflammation, immune and fibrosis related pathways may be involved in the development of left ventricular noncompaction.