Role of Cardiac Dysfunction and Injury in High-Risk Acute Respiratory Distress Syndrome Subphenotypes

心脏功能障碍和损伤在高危急性呼吸窘迫综合征亚表型中的作用

• 批准号: 10537702
• 负责人: Pablo Sanchez
• 金额: $ 7.86万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-09-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10537702
• 关键词: Acute Respiratory Distress Syndrome; Affect; Angiopoietin-2; Angiopoietins; Biological Markers; Cardiac; Cardiopulmonary; Cardiovascular system; Clinical; Clinical Data; Clinical Trials; Critical Illness; Data; Disease; Echocardiography; Endothelium; Functional disorder; Goals; Heart Injuries; Heart failure; Hypoxemia; Hypoxemic Respiratory Failure; Incidence; Inflammatory; Intervention; Knowledge; Lead; Lung; Lung diseases; Measures; Mechanical ventilation; Mediating; Mediator of activation protein; Mentorship; Modeling; Modification; Morbidity - disease rate; Myocardial dysfunction; Pathway interactions; Patients; Pattern; Pharmacological Treatment; Pharmacology; Phenotype; Plasma; Process; Pulmonary Hypertension; Research; Respiratory Failure; Right Ventricular Dysfunction; Right Ventricular Function; Right ventricular structure; Risk; Role; SARS-CoV-2 infection; Sampling; Serum; Severity of illness; Shock; Stress; Syndrome; TIE-2 Receptor; Testing; Troponin I; Vascular Permeabilities; Vascular remodeling; Work; angiogenesis; antagonist; attributable mortality; biobank; candidate marker; disease phenotype; high risk; lung injury; lung vascular injury; mortality; multiorgan injury; myocardial injury; novel; pulmonary arterial hypertension; pulmonary vascular disorder; recruit; response; sepsis induced ARDS; vascular endothelium permeability; vascular injury

Project Summary The Acute Respiratory Distress Syndrome (ARDS) is characterized by fulminant hypoxemic respiratory failure. Its high morbidity and mortality exceed what can be attributed to hypoxemia and lung injury and, indeed, multiorgan injury, cardiac dysfunction and shock serve as significant drivers in this regard. Consistently, a hyperinflammatory phenotype of ARDS is associated with higher mortality and differential response to management strategies. Whether cardiac injury in ARDS is modulated by an inflammatory phenotype has not been previously evaluated. Additionally, Angiopoietin-2 (ANG2) is an important marker of vascular injury in ARDS and predictive of mortality in heart failure and pulmonary hypertension. Therefore, ANG2 is an excellent candidate biomarker for evaluating cardiac injury and dysfunction in ARDS, but this has not been evaluated to date. My central hypothesis is that the high-risk inflammatory sub-phenotype and elevated ANG2 in ARDS are associated with worse cardiac injury and right ventricular dysfunction, and these contribute independently to the elevated mortality of affected patients. AIM 1: Determine the extent to which hyper and hypo-inflammatory ARDS phenotypes predict differential cardiac injury and dysfunction. Using Latent Class Analysis of baseline serum biomarker and clinical data, ARDS patients will be clustered into inflammatory phenotypes. High-sensitivity troponin I elevation and echocardiography will be used to assess cardiac injury and right ventricular dysfunction, respectively. I will then model the effect of cardiac injury and dysfunction on 28-day mortality among the hyperinflammatory subphenotype. AIM 2: Determine the extent to which elevated angiopoietin-2 levels in ARDS predict differential cardiac injury and dysfunction. I will measure ANG2 levels in ARDS patients along with high-sensitivity troponin I and determine right ventricular dysfunction through echocardiography. I will then model the effect of cardiac injury and dysfunction on 28-day mortality among patients with ANG2 elevation. In summary, I will determine the impact that a hyperinflammatory ARDS phenotype and ANG2 elevation have on cardiac injury, dysfunction, and attributable mortality. This knowledge will be crucial in understanding the cardiopulmonary interaction in this disease process and can pave the way for introducing management strategies for patients with right ventricular dysfunction in ARDS.

项目概要 急性呼吸窘迫综合征（ARDS）的特点是暴发性低氧血症性呼吸困难 失败。其高发病率和死亡率超过了低氧血症和肺损伤，并且， 事实上，多器官损伤、心脏功能障碍和休克是这方面的重要驱动因素。 一致地，ARDS 的高炎症表型与较高的死亡率和差异相关 对管理策略的响应。 ARDS 中的心脏损伤是否受炎症调节 之前尚未评估过表型。此外，Angiopoietin-2 (ANG2) 是一个重要的标志物 ARDS 中血管损伤的评估以及心力衰竭和肺动脉高压死亡率的预测。所以， ANG2 是评估 ARDS 心脏损伤和功能障碍的绝佳候选生物标志物，但是 迄今为止尚未对此进行评估。我的中心假设是高风险炎症亚表型 ARDS 中 ANG2 升高与更严重的心脏损伤和右心室功能障碍相关，并且 这些独立因素导致受影响患者的死亡率升高。 目标 1：确定高炎症和低炎症 ARDS 表型预测的程度 不同的心脏损伤和功能障碍。使用基线血清生物标志物的潜在类别分析和 临床数据显示，ARDS患者将聚集成炎症表型。高敏肌钙蛋白 I 升高 和超声心动图将分别用于评估心脏损伤和右心室功能障碍。我会 然后模拟心脏损伤和功能障碍对高炎症患者 28 天死亡率的影响 亚表型。 目标 2：确定 ARDS 中血管生成素 2 水平升高预测心脏差异的程度 损伤和功能障碍。我将测量 ARDS 患者的 ANG2 水平以及高敏肌钙蛋白 I 并通过超声心动图确定右心室功能障碍。然后我将模拟心脏的影响 损伤和功能障碍对 ANG2 升高患者 28 天死亡率的影响。 总之，我将确定高炎症 ARDS 表型和 ANG2 升高的影响 心脏损伤、功能障碍和死亡率。这些知识对于理解 这种疾病过程中的心肺相互作用，可以为引入管理铺平道路 ARDS 中右心室功能障碍患者的治疗策略。