Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, Australia; Department of Cardiology, Blacktown Hospital, Blacktown, Australia.
JACC Cardiovasc Imaging. 2021 Dec;14(12):2288-2300. doi: 10.1016/j.jcmg.2021.05.020. Epub 2021 Jul 14.
The aim of this work was to identify the key morphological and functional features in secondary mitral regurgitation (sMR) and their prognostic impact on outcome.
Secondary sMR in patients with heart failure and reduced ejection fraction typically results from distortion of the underlying cardiac architecture. The morphological components which may account for the clinical impact of sMR have not been systematically assessed or correlated with clinical outcomes.
Morphomic and functional network profiling were performed on a cohort of patients with stable heart failure optimized on guideline-based medical therapy. Principal component (PC) analysis and subsequent cluster analysis were used to condense the morphomic and functional data first into PCs with varimax rotation (PC) and second into homogeneous clusters. Clusters and PCs were tested for their correlations with clinical outcomes.
Morphomic and functional data from 383 patients were profiled and subsequently condensed into PCs. PC 1 describes high loadings of left atrial morphological information, and PC 2 describes high loadings of left ventricular (LV) topology. Based on these components, 4 homogeneous clusters were derived. sMR was most prominent in clusters 3 and 4, with the morphological difference being left ventricular size (median end-diastolic volume 188 mL [interquartile range: 160 mL-224 mL] vs 315 mL [264 mL-408 mL]; P < 0.001). Clusters were associated with mortality (P < 0.001), but sMR remained independently associated with mortality after adjusting for the clusters (adjusted HR: 1.42; 95% CI: 1.14-1.77; P < 0.01). The detrimental association of sMR with mortality was mainly driven by cluster 3 (HR: 2.18; 95% CI: 1.32-3.60; P = 0.002), the "small LV cavity" phenotype.
These results challenge the current perceptions that sMR in heart failure with reduced ejection fraction results exclusively from global or local LV remodeling and are suggestive of a potential role of the left atrial component. The association of sMR with mortality cannot be purely attributed to cardiac morphology alone, supporting other complementary key aspects of mitral valve closure consistent with the force balance theory. Unsupervised clustering supports the association of sMR with mortality predominantly driven by the small LV cavity phenotype, as previously suggested by a conceptional framework and termed disproportionate sMR.
本研究旨在确定继发性二尖瓣反流（sMR）的关键形态学和功能特征及其对预后的影响。
心力衰竭伴射血分数降低患者的继发性 sMR 通常是由基础心脏结构变形引起的。尚未系统评估或关联临床结局来评估可能导致 sMR 临床影响的形态学成分。
对接受基于指南的优化药物治疗的稳定心力衰竭患者队列进行形态学和功能网络分析。主成分（PC）分析和随后的聚类分析用于首先将形态学和功能数据压缩成具有方差最大化旋转（PC）的 PC，然后压缩成同质聚类。对聚类和 PC 进行测试，以评估其与临床结局的相关性。
对 383 例患者的形态学和功能数据进行了分析，并进一步压缩成 PC。PC1 描述了左心房形态学信息的高负荷，PC2 描述了左心室（LV）拓扑结构的高负荷。基于这些成分，得出了 4 个同质聚类。sMR 在聚类 3 和 4 中最为明显，形态差异为左心室大小（中位数舒张末期容积 188mL[四分位间距 160mL-224mL]与 315mL[264mL-408mL]；P<0.001）。聚类与死亡率相关（P<0.001），但在调整聚类后，sMR 仍然与死亡率独立相关（调整后的 HR：1.42；95%CI：1.14-1.77；P<0.01）。sMR 与死亡率的不良关联主要由聚类 3（HR：2.18；95%CI：1.32-3.60；P=0.002）即“小 LV 腔”表型驱动。
这些结果挑战了当前关于射血分数降低的心力衰竭中 sMR 仅源自于整体或局部 LV 重塑的观念，并提示左心房成分可能发挥潜在作用。sMR 与死亡率的关联不能仅仅归因于心脏形态，这支持了二尖瓣关闭的其他互补关键方面与力平衡理论一致。无监督聚类支持 sMR 与死亡率的关联主要由先前概念框架提出并称为不成比例的 sMR 的小 LV 腔表型驱动。
