R01HL170019

Cardiac Imaging of Neuro-Embolic Mechanisms in Atriopathies Causing Stroke (CINEMAS) - Project Summary
Stroke is one of the leading causes of death and remains a major cause of disability with over 25 million individuals worldwide living with its consequences. Manifest atrial fibrillation (AF) accounts for 10% of all strokes, predominantly due to thromboembolism from the left atrium (LA).
Despite thorough diagnostic evaluation, 20-30% of ischemic strokes are classified as cryptogenic or of unknown cause. Most cryptogenic strokes have an embolic appearance, known as embolic stroke of undetermined source (ESUS).
A substantial portion of patients with ESUS will eventually be diagnosed with AF. Recent findings support the notion that an underlying disease of the LA (atrial cardiopathy), which may lead to AF, may also independently result in thrombus formation and increase stroke risk in the absence of AF.
LA appendage (LAA) stasis is linked to atrial thrombus formation as part of Virchow’s triad. Our preliminary work on LA 4D flow MRI (4DMRI) provides a novel noninvasive tool that assesses LAA stasis and could provide a new paradigm for stroke prevention.
Other biomarkers of atrial cardiopathy have already been associated with greater risk of development of AF and stroke, including atrial size/morphology, ECG P wave morphology, atrial strain on echocardiography, epicardial adipose tissue (EAT), troponin and N terminal pro-brain natriuretic peptide levels.
Yet, none are currently used for clinical decision making. The overall goal of this research is to identify clinical and mechanistic characteristics of 4DMRI-derived LAA stasis in order to identify optimal strategies to prevent recurrent stroke in patients with ESUS.
It is anticipated that this mechanistic assessment for risk of atrial thrombus formation will also provide improved utility for stroke prevention in AF. We will prospectively study patients with ESUS at 4 experienced centers with heart-brain MRI, assessing LAA stasis by 4DMRI and other atrial cardiopathy markers in a comprehensive manner.
Specific aims are to: 1) evaluate 4DMRI LA/LAA stasis and other atrial cardiopathy biomarkers in patients with ESUS (group 1, N=229), cardioembolic stroke due to AF (group 2, N=80), no stroke or AF (group 3, N=80), and no stroke but with AF (group 4, N=80). We will assess the diagnostic utility of LA/LAA stasis and other atrial cardiopathy biomarkers for cardioembolic stroke due to AF;
2) assess the clinical factors predicting progression of LA/LAA stasis in 229 ESUS patients by repeating MRI at 2 years;
3) determine whether LAA stasis and/or other atrial cardiopathy biomarkers are predictors of recurrent ischemic stroke (primary endpoint) and new AF (secondary) in 229 patients with ESUS. We hypothesize that LAA stasis will be the strongest independent predictor of recurrent ischemic stroke.
This proposal, Cardiac Imaging of Embolic Mechanisms in Atriopathies Causing Stroke (CINEMAS), focuses on optimizing the diagnosis of atrial cardiopathy in patients with ESUS. Improved diagnosis with a strong link to clinical endpoints can broaden the options for primary and secondary prevention of stroke and AF.

University Of Miami

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. 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]

Miami, Florida 331362107 United States

Single Zip Code

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

Amendment Since initial award the total obligations have increased 91% from $1,815,762 to $3,473,396.