Unraveling Flow-Dynamic Characterization of the Ascending Aorta and Left Ventricle in Bicuspid Aortic Valve Pathologies via 4D Flow MRI

Abstract

Bicuspid aortic valve (BAV) disease is the most common congenital and clinically significant cardiac anomaly. It is strongly associated with progressive aortopathy, an increased propensity for both obstructive and regurgitant complications, and ventricular remodeling. These observations underscore the complex and heterogeneous natural history of BAV, necessitating vigilant lifelong monitoring and individualized management strategies. Current clinical surveillance relies primarily on anatomical indices, such as aortic diameter, and global left ventricular functional parameters, which insufficiently capture the complex hemodynamic burden driving disease progression. Although fluid mechanics has long been applied to study the impact of native valve function on myocardial and aortic performance, its clinical translation has been limited by conceptual gaps and the lack of practical tools for data acquisition. Advanced magnetic resonance imaging (MRI), particularly time-resolved three-dimensional phase-contrast velocity encoding (4D flow MRI), enables comprehensive quantification of blood flow and ventricular energetics, offering the potential for novel biomarkers to improve risk stratification and management. This thesis investigated the ascending aorta and left ventricle in BAV patients across varying valvular phenotypes and lesion severities, integrating flow-derived metrics with functional and structural assessments. In the first study, regional diastolic wall shear stress and flow displacement at the aortic root were linked to root dilation in patients with regurgitant BAV, highlighting mechanistic drivers of root remodeling. The second study demonstrated that local intracardiac pressure gradients, uniquely quantified using 4D Flow MRI, are more sensitive markers of early diastolic dysfunction in BAV patients with mild regurgitation and preserved ejection fraction, compared with global decomposed flow components. The third study introduced a multitechnique framework that integrated 4D flow-derived kinetic energy, and viscous energy loss, with diastolic strain rates, uncovering impaired efficiency and early dysfunction across stages of regurgitation. Finally, ascending aortic hemodynamics were shown to be associated with left ventricular remodeling, establishing a direct coupling between vascular and ventricular pathophysiology in BAV. Together, these studies provide novel mechanistic insights into the interplay between valvular lesions, aortic hemodynamics, and ventricular remodeling. They underscore the limitations of diameter-based surveillance and support the incorporation of flow-derived biomarkers, such as kinetic energy, energy loss, wall shear stress, and intracardiac pressure gradients, into future clinical evaluation frameworks. Furthermore, these findings establish a foundation for applying 4D Flow MRI-derived biomarkers in BAV and other complex congenital and acquired cardiovascular conditions, underscoring the need to evaluate their utility in longitudinal monitoring and multimodality comparisons.