R01HL153724

The state of energy in the right ventricle of patients with pulmonary arterial hypertension - Project Summary/Abstract

Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease with a high mortality rate. In most cases, PAH-induced chronic pressure overload leads to right ventricle (RV) failure. Right heart catheterization (RHC) is currently the gold standard test for PAH diagnosis and follow-up. Furthermore, repeated RHC should be considered in patients who experience unexplained clinical deterioration during their clinical course or for periodic follow-up over time. Yet many centers across the world do not routinely perform RHC during follow-up, for a variety of potential reasons, including its invasive nature, cost, or availability.

We have recently developed 3D echocardiographic particle image velocimetry (ECHO-PIV), which allows high-temporal volumetric assessment of RV hemodynamics. In combination with standard 3D speckle tracking, 3D ECHO-PIV enables a comprehensive assessment of hemodynamics and energy state (ventricular kinetic energy/work and viscous energy dissipation) in the RV. The RV energy state reflects the structural and functional changes in the RV that may occur due to PAH. Thus, it can be used as a load-independent measure to assess RV function and monitor disease progression/regression in PAH patients.

The project's global hypothesis is that in PAH patients' follow-up, changes in the RV energy state: (1) reflect changes in RHC-derived pulmonary arterial pressures, and (2) are associated with changes in patients' clinical status such that it can be used to monitor disease progression and regression. Given that in more advanced disease, RV dysfunction is present, we will gather a prospective, ethnically diverse cohort of 210 subjects at Cedars-Sinai Medical Center: 70 PAH patients with normal RV function, 70 PAH patients with RV dysfunction, and 70 healthy control subjects.

The following specific aims will be accomplished:

Specific Aim 1: Investigate the accuracy of 3D ECHO-PIV in characterizing 4D flow hemodynamics in the RV using 4D flow CMR as a reference standard and assess test/retest reproducibility of 3D ECHO-PIV in PAH.

Specific Aim 2: Determine the relationship between the noninvasively derived RV energy state and RHC-derived parameters in following up PAH patients and test whether changes in the RV energy state reflect changes in the RHC-derived pulmonary arterial pressures in PAH patients with and without RV dysfunction.

Specific Aim 3: Investigate the feasibility of noninvasive imaging-derived RV energy state for monitoring disease progression/regression in PAH patients.

The success of the proposed studies will establish 3D ECHO-PIV as a tool for assessment of PAH patients and will: (1) determine the relationship between noninvasive RV imaging and invasive RHC-based hemodynamics, (2) establish whether changes in noninvasive RV energy state reflect changes in the RHC-derived parameters in PAH patients, and (3) facilitate monitoring of disease progression/regression by noninvasive RV energy state in lieu of invasive RHC (current clinical gold standard).

Irvine University Of California

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

California United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 367% from $671,932 to $3,136,082.