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

> **NIH NIH F32** · STANFORD UNIVERSITY · 2022 · $61,416

## Abstract

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.

## Key facts

- **NIH application ID:** 10537702
- **Project number:** 1F32HL160103-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Pablo Sanchez
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $61,416
- **Award type:** 1
- **Project period:** 2022-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537702

## Citation

> US National Institutes of Health, RePORTER application 10537702, Role of Cardiac Dysfunction and Injury in High-Risk Acute Respiratory Distress Syndrome Subphenotypes (1F32HL160103-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10537702. Licensed CC0.

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