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.