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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结