Background Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology. Objective We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms. Methods In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5–2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e’ ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes. Results We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e’ ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40. Conclusion Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

中文翻译：

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血浆蛋白质组与慢性心力衰竭患者的左心室和左心房功能参数相关

背景 检查射血分数降低心力衰竭 (HFrEF) 异质性综合征中的全身生物过程（如循环蛋白所反映的）与超声心动图特征的关系，可能会为心力衰竭病理生理学提供见解。目的 我们研究了 HFrEF 患者中 4210 种重复测量的循环蛋白与重复测量的超声心动图参数以及左心房压力 (LAP) 升高之间的联系，以深入了解潜在机制。方法 在 173 名 HFrEF 患者中，我们在中位随访 2.7（IQR：2.5-2.8）年期间每六个月进行一次超声心动图检查并每三个月进行一次血液采样。我们研究了与左心室超声心动图参数（左心室射血分数[LVEF]、整体纵向应变[GLS]）、左心房功能（左心房储备应变[LASr]）和升高的LAP（E/e'）相关的循环蛋白比率> 15），并使用基因富集分析来识别潜在的病理生理过程。结果 我们发现 723、249、792 和 427 个重复测量的蛋白质，分别与 LVEF、GLS、LASr 和 E/e' 比率显着相关。与 LASr 相关的蛋白质反映了主要与细胞外基质 (ECM) 有关的病理生理机制。与 GLS 相关的蛋白质反映了心血管生物过程和疾病，而与 LVEF 相关的蛋白质则反映了交感神经系统的过程。此外，49 种蛋白质与 LAP 升高相关；校正 LVEF 后，剩下三种蛋白质：Cystatin-D、Fibulin-5 和 HSP40。结论 HFrEF 患者的循环蛋白与不同超声心动图参数之间存在不同的关联。这些发现表明，如血浆蛋白质组所反映的，涉及心房和心室功能障碍的途径是不同的。