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

项目摘要 急性呼吸窘迫综合征(ARDS)的特征是暴发性低氧血症 失败了。它的高发病率和死亡率超过了可归因于低氧血症和肺损伤的因素， 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。 一直以来，ARDS的高炎性表型与较高的死亡率和分化程度相关。 对管理策略的回应。急性呼吸窘迫综合征的心脏损伤是否受炎症调节 以前还没有对表型进行过评估。此外，血管生成素-2(ANG2)也是一个重要的标志物 ARDS的血管损伤和心力衰竭和肺动脉高压的死亡率的预测。因此， 血管紧张素转换酶2是评估ARDS心脏损伤和功能障碍的一个很好的候选生物标志物，但 到目前为止，还没有对此进行评估。我的中心假设是高危炎症性亚型 ARDS患者血管紧张素转换酶2升高与更严重的心脏损伤和右心功能不全相关。 这些都是造成受影响患者死亡率上升的独立原因。 目的1：确定高炎症和低炎症ARDS表型预测的程度 区分心脏损伤和功能障碍。基线血清生物标志物潜伏期分析与临床应用 临床资料显示，ARDS患者将分为炎症表型。高敏肌钙蛋白I升高 超声心动图将分别用于评估心脏损伤和右心功能不全。这就做 然后模拟心脏损伤和功能障碍对高炎症者28天死亡率的影响 亚型。 目的2：确定ARDS患者血管生成素-2水平升高在多大程度上预测心脏分化 受伤和功能障碍。我将检测ARDS患者的血管生成素2水平以及高敏肌钙蛋白I 并通过超声心动图确定右心功能不全。然后我将模拟心脏的作用 ANG2升高患者的损伤和功能障碍对28天死亡率的影响。 总而言之，我将确定高炎症性ARDS表型和ANG2升高的影响 心脏损伤、功能障碍和归因性死亡率。这方面的知识对于理解 心肺互动在这一疾病过程中的作用，并可为引入管理铺平道路 ARDS右心功能不全患者的治疗策略。

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.