Heart Valve Biomechanics and Underlying Mechanobiology

Abstract

Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling. We begin with an overview of the fundamentals of heart valve physiology and the characteristics and functions of valve interstitial cells (VICs). We then provide an overview of current experimental and computational approaches that connect VIC mechanobiological response to organ- and tissue-level deformations and improve our understanding of the underlying functional physiology of heart valves. We conclude with a summary of future trends and offer an outlook for the future of heart valve mechanobiology, specifically, multiscale modeling approaches, and the potential directions and possible challenges of research development.

A comprehensive pipeline for multi‐resolution modeling of the mitral valve: Validation, computational efficiency, and predictive capability

“…To better understand the biomechanical response of the tissue, the model needs to be extended to accurately model these phenomena . Furthermore, to elucidate the mechanobiological drivers of the growth and remodeling, it is important to connect the organ‐level tissue response to the cellular‐level response . This would enable us to investigate the changes in phenotypic state of MV interstitial cells and analyze their response to the mechanical stress overloads and surgical interventions.…”

A noninvasive method for the determination of in vivo mitral valve leaflet strains

“…The present study builds upon over a century of investigations into MV mechanics and owes much to recent achievements in the development of high‐fidelity computational models of the MV . Moreover, the overarching objective of devising noninvasive methods to estimate MV strains in vivo is motivated by an increasingly compelling body of evidence that supports hypotheses of bidirectional causal links between tissue‐level deformations and cell‐mediated growth and remodeling events . It is thus strongly believed that accounting for these interconnected phenomena is paramount to the accurate prediction of clinical events, such as post‐MI MV/ventricular remodeling and postsurgical MV repair outcomes .…”

“…The homeostatic maintenance of MV leaflet tissue composition and microstructure, primarily mediated by interstitial cell deformation, has been shown to depend on direction‐specific loading patterns . For a physiologically relevant interpretation of strains, it is thus necessary to examine each component of the strain tensor individually.…”

“…Then, element‐wise material directions were determined in the open state as follows: (1) The transmural direction was defined as the face normal vector, oriented outwardly from the leaflet's ventricular surface; (2) the radial direction was computed through a 90° rotation of toward using where , such that lies tangent to the element face and approximately orthogonal to the annular boundary; and (3) the circumferential direction was defined as . This procedure yielded an orthogonal local coordinate system for each element consistent with conventional anatomic nomenclature . Note that although the local material directions were originally determined using the open‐state geometry, they are defined with respect to the current configuration and thus convect when the mesh is deformed during FE simulations of closure.…”

“…Such alterations place the MV in a nonphysiological loading state, leading to valvular tissue growth and remodeling . In light of this, recent studies have begun to elucidate links between MV function at the organ level and the mechanobiological responses of the underlying MV interstitial cells, which ultimately drive remodeling . These investigations have uncovered and quantified detailed relationships between MV leaflet stretch and interstitial cell deformation.…”