Investigations of the Mechanical Properties and Microstructure of the Atrioventricular Heart Valve Leaflets

Abstract

Atrioventricular heart valves (AHVs), namely the mitral and tricuspid valves, regulate unidirectional blood flow from the atria to the ventricles in the left and right sides of the hearts, respectively. These valves can be afflicted by diseases which degrade the tissue microstructure and cause blood backflow, or valve regurgitation. This regurgitation causes poorer prognoses and higher mortality rates for patients. However, no current treatments for valve regurgitation offer an ideal solution, though recent research efforts have focused on developing novel treatment techniques with improved long-term therapeutic outcomes. For these applications, a comprehensive understanding of the mechanical behaviors and microstructure of the native heart valve leaflet tissues is essential. This thesis research used biaxial mechanical testing methods to provide novel insights into the complexity of the AHV leaflet mechanics, revealing: (i) the characteristic nonlinear and anisotropic mechanical response of the AHV leaflets, with radial stretches 30.7% higher than circumferential stretches on average across all AHV leaflets, (ii) the higher stiffness of the mitral valve leaflets (avg. circumferential- and radial-direction stretches of 1.224 and 1.599, respectively, under physiological loading) compared to their more compliant tricuspid counterparts (avg. circumferential- and radial-direction stretches of 1.298, 1.708, respectively, under physiological loading), (iii) the minimal loading-rate response of the AHV leaflets and the anisotropic changes in tissue response with varied testing temperature, and (iv) the regional variance in the mechanical properties of the AHV anterior leaflets, with increased mechanical anisotropy in the center of the tissues and more isotropic mechanics nearer to the leaflet boundaries (avg. anisotropy index of 1.087 in central regions vs. 1.017 in edge regions). To complement these tissue mechanics studies, a polarization-based quantitative imaging device was developed to assess the reorientation of microstructural collagen fibers in response to mechanical loading. The device was applied to assess the representative mitral valve anterior leaflet, for the first time illuminating the spatial heterogeneity and load-dependence of the leaflet collagen microstructures, with observed average degree of optical anisotropy, which describes the degree of collagen fiber alignment, increasing from 0.042 in an unloaded tissue to 0.086 in a tissue under predicted physiological loading. These investigations and this novel system provide an essential first step toward elucidating the mechanics-microstructure relationship in the AHV leaflets. At the same time, our studies contribute to an improved understanding of valve leaflet tissue function, with the overarching goal of advancing treatment options for patients with valve regurgitation.