On the in vivo function of the mitral heart valve leaflet: insights into tissue–interstitial cell biomechanical coupling

Abstract

There continues to be a critical need for developing data-informed computational modeling techniques that enable systematic evaluations of mitral valve (MV) function. This is important for a better understanding of MV organ-level biomechanical performance, in vivo functional tissue stresses, and the biosynthetic responses of MV interstitial cells (MVICs) in the normal, pathophysiological, and surgically repaired states. In the present study, we utilized extant ovine MV population-averaged 3D fiducial marker data to quantify the MV anterior leaflet (MVAL) deformations in various kinematic states. This approach allowed us to make the critical connection between the in vivo functional and the in vitro experimental configurations. Moreover, we incorporated the in vivo MVAL deformations and pre-strains into an enhanced inverse finite element modeling framework (Path 1) to estimate the resulting in vivo tissue prestresses [Formula: see text] and the in vivo peak functional tissue stresses [Formula: see text]. These in vivo stress estimates were then cross-verified with the results obtained from an alternative forward modeling method (Path 2), by taking account of the changes in the in vitro and in vivo reference configurations. Moreover, by integrating the tissue-level kinematic results into a downscale MVIC microenvironment FE model, we were able to estimate, for the first time, the in vivo layer-specific MVIC deformations and deformation rates of the normal and surgically repaired MVALs. From these simulations, we determined that the placement of annuloplasty ring greatly reduces the peak MVIC deformation levels in a layer-specific manner. This suggests that the associated reductions in MVIC deformation may down-regulate MV extracellular matrix maintenance, ultimately leading to reduction in tissue mechanical integrity. These simulations provide valuable insight into MV cellular mechanobiology in response to organ- and tissue-level alternations induced by MV disease or surgical repair. They will also assist in the future development of computer simulation tools for guiding MV surgery procedure with enhanced durability and improved long-term surgical outcomes.

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

“…Dashed lines indicate the full range of each parameter observed across six total MV specimens in previous studies that have utilized this model form. 21,22,60,77 In the context of our novel image-based strain estimation method, while the use of a material model is important to regularize the resulting stretch field and impose physical realism, these results demonstrate that the accuracy of the method is only mildly dependent on the specific choice of material parameters and that the method consistently delivers stretch estimates within 10% of their true value ) .…”

“…To maximally account for intersubject variability in material properties, each parameter was varied sufficiently to span beyond the full range observed across six total MV specimens in four previous studies that have utilized the same fiber-based structural model. 21,22,60,77 For each case, E ub was adjusted such that total fiber recruitment occurred at approximately 400 kPa of stress, as this quantity has been shown to be consistent across heart valve tissues. 75,92 The results showed that over the observed range of material responses, our novel image-based strain determination method provided stretch estimates with an average absolute error less than 10% ( Figure A2).…”

“…[14][15][16][17][18][19][20] 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. 19,[21][22][23][24][25][26] These investigations have uncovered and quantified detailed relationships between MV leaflet stretch and interstitial cell deformation. Furthermore, specific cellular deformation patterns have been associated with concurrent remodeling in the extracellular matrix of the MV leaflets, mainly via biosynthetic changes to the tissue's collagen and elastin networks.…”

“…32,34 As a result, sonomicrometry has historically been more popular for heart valve applications, which require high spatial and temporal resolutions due to the valves' small size and rapid movement. 22,[35][36][37][38][39][40][41] Regardless of their individual strengths, however, all marker-based approaches suffer from two major limitations: (1) Marker implantation requires highly invasive and tedious surgery, making it infeasible for human studies or clinical use, and (2) marker arrays only encompass a limited area of tissue, and extraction of local strains over the entire leaflet surface would require an impractical number of markers.…”

“…[16][17][18][19]23,24 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. 15,22,[86][87][88] To achieve these goals, noninvasive methods of leaflet strain estimation are essential for a variety of applications, including functional assessments, model development and validation, and presurgical and postsurgical functional metrics. We also note that, to date, we do not have a complete understanding of MV tissue deformation over the entire leaflet.…”