Anomalous coronary ischemia evaluation with computational modeling and magnetic-resonance imaging

Active Project Grant Awarded Last action

Award ID
F32HL184610
Recipient
Awarding agency
Obligated
$87,148

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 0% complete
Place of performance
Cleveland, OH 44195, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Anomalous aortic origin of a coronary artery (AAOCA) is a congenital defect in which a coronary artery arises from the incorrect aortic sinus. During exercise, the aberrant proximal course may become compressed, leading to myocardial ischemia and sudden cardiac death. To evaluate the physiological impact of the anomaly under pharmacologic dobutamine stress, our center uses positron emission tomography (pet) to measure myocardial blood flow reserve (MBFR) and invasive cardiac catheterization to measure the instantaneous wave-free ratio (IFR). While IFR provides a direct and precise measure of pressure loss across the anomalous coronary origin, IT can be influenced by concomitant distal coronary disease, such as atherosclerosis or microvascular dysfunction. The central clinical challenge is how to interpret these ischemia metrics in the presence of distal disease and determine the threshold of these metrics at which patients would benefit from surgical intervention. To address this, we utilize computational fluid-structure interaction (FSI) simulations that we developed for noninvasively IFR prediction. These patient-specific FSI models serve as a powerful platform to test in silico the hemodynamic effects of unknown factors, such as distal coronary disease. In parallel, we have advanced diffusion tensor cardiac magnetic resonance imaging (DT-CMR), which has enabled early detection of ischemia- induced microstructural remodeling, characterized by higher mean diffusivity (MD) and lower fractional anisotropy (FA), before fibrotic changes are visible on conventional CMR with T1 mapping and late gadolinium enhancement (LGE). This proposal tests the hypothesis that, in adults with AAOCA, distal coronary disease worsens ischemia (with different effects on IFR and MBFR), and that ischemia leads to adverse myocardial remodeling evaluated by CMR. In aim 1, I will use patient-specific FSI simulations to test whether increasing the prescribed distal coronary resistance significantly increases the IFR and decreases MBFR. We will also assess whether automatically adjusting the distal resistance, until the simulation achieves the pet-measured MBFR, will improve IFR prediction accuracy. In aim 2, I will assess for evidence of adverse myocardial remodeling in patients with AAOCA compared to age-matched healthy participants. Furthermore, we test whether ischemia severity (lower IFR and lower MBFR) results in more significant downstream microstructural remodeling (higher MD and lower FA) and fibrosis (T1 mapping and LGE). Successful completion of these aims will establish a framework to adjust ischemia thresholds in the presence of distal coronary disease, and may support DT-CMR as a sensitive tool for ischemia detection in AAOCA. These findings will advance our mechanistic understanding of AAOCA, improve diagnostic precision, and lay the groundwork for noninvasive, individualized risk stratification to guide surgical decision-making.

Quick answers

Who received award F32HL184610?

F32HL184610 was awarded to Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University by National Heart Lung and Blood Institute (National Institutes of Health) on December 1, 2026.

How much is award F32HL184610 worth?

$87,148 has been obligated on F32HL184610.

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