主动脉瓣反流瓣膜置换术后左室收缩功能转归: 三维斑点追踪超声评价与miRNA检测的同步研究

The current indications of aortic valve replacement (AVR) for aortic regurgitation (AR) in asymptomatic patients remain based on experts’ opinions rather than evidences from prospective clinical trials. According to recent European Society of Cardiology (ESC) and American Heart Association (AHA) guidelines, prospective clinical study using advanced echocardiographic techniques combined with biomarkers at molecular and genomic level has the great promise for resolving the current controversy. Advanced three-dimensional speckle tracking echocardiography (3D-STE) provides comprehensive assessment of left ventricular (LV) volume, global and regional myocardial contraction, and is more sensitive than conventional LV function assessment methods using two-dimensional echocardiography. miRNA has been established as an important regulator in pathology of chronic cardiac failure, and also been shown its characteristic as a biomarker. Our project is aimed to perform a prospective two-year assessment in patients undergoing AVR for AR. We hope to explore the changes in LV volume and function after AVR using 3D-STE, and establish the prognostic value of pre-op 3D-STE to post-op LV systolic function recovery. At the same time, we will quantify the expression level of selected heart failure related miRNAs from myocardium and plasma. The time related changes in miRNA expression will be analyzed. The clinical prognostic value of miRNA with respect to LV functional changes will be examined. We expect this translational study to provide significant scientific evidences for improving clinical decision making of AVR for AR, by our unique combination of biomarker and echocardiography.

慢性主动脉瓣反流（AR）行主动脉瓣膜置换术（AVR）的现行手术指征中，对于患者是否需要在症状或左室功能不全出现前行AVR，尚无定论。欧美新近瓣膜手术指南建议使用超声新技术评估左室功能，并寻找有效生物标记物，以提高对手术指征的掌握。三维斑点追踪超声心动图（3D-STE）能够精细评估左室容积、整体泵功能和局部心肌力学信息。miRNA作为重要的生物学标记物，已被证实精细调控着慢性心力衰竭的多个病理生理环节。本课题使用3D-STE前瞻性研究行AVR手术的慢性AR患者手术前和术后2年的心脏功能演变，以及3D-STE对于AVR手术的预后价值。检测心肌组织和血浆中心衰相关的数种miRNA在AR患者中的表达和AVR手术前后演变规律。通过同步研究miRNA表达与超声指标的变化规律与相关性，确立miRNA预测AVR术后左室功能改变的价值。从分子水平和超声诊断两方面，为AR患者行AVR手术的指征掌握提供证据。

三维斑点追踪超声心动图（3D-STI）能够精细评估左室整体和局部心肌力学信息，miRNAs参与了心衰发生的多个环节。本课题通过分析重度主动脉瓣反流（AR）患者行主动脉瓣置换手术（AVR）前后3D-STI和常规左室收缩功能超声指标，探讨了AR患者术前心功能受损、术后心功能转归及围术期临床预后的超声评价。结果显示：（1）重度AR患者中，术前LVEF减低者所有左室节段的各向应变均减低；而LVEF正常者，整体环向应变、基底段的应变和旋转尚处正常范围，对于维持LVEF起到重要作用。（2）术后早期， 较术前LVEDV减小，LVEF下降，各应变指标均减低，而整体扭转力增加。左室节段应变分析提示，径向应变减低累及全部左室节段，而长轴应变减低只发生于基底段，提示左室短轴较长轴功能减低更为显著。（3）术中及术后早期发生心血管不良事件的患者较无不良事件患者术前虽然LVEF、左室球形化指数、整体扭转力无显著差异，但LVEDV、LVESV和LVMI更高，长轴、环向和径向应变更低。多因素回归分析提示术前左室长轴整体应变是术中及术后发生心血管不良事件的唯一独立预测因子。（4）miRNAs检测提示AR患者循环血中miR—320a的表达较正常组升高，且miR-320a与LVEDV呈负相关趋势。综合上述结果，本项目研究显示3DE-STI超声指标能从三个方向，多个节段全面评价左室功能，较常规左室容积和射血分数指标更为精细和敏感，可提供AR术前的亚临床左室收缩功能受损信息和机制、术后心功能转归规律和机制以及围术期不良事件预测。同时AR患者miR-320a的表达有升高，且与左室容积指标有相关性，提示生物学指标可以尝试与超声指标结合判断，提高对疾病的整体认识。项目资助发表SCI论文2篇，中文核心期刊论文1篇，待发表3篇。培养硕士研究生1名，并已顺利获得硕士学位。