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Ventricular growth is widely considered to be an important feature in the adverse progression of heart diseases, whereas reverse ventricular growth (or reverse remodeling) is often considered to be a favorable response to clinical intervention. In recent years, a number of theoretical models have been proposed to model the process of ventricular growth while little has been done to model its reverse. Based on the framework of volumetric strain-driven finite growth with a homeostatic equilibrium range for the elastic myofiber stretch, we propose here a reversible growth model capable of describing both ventricular growth and its reversal. We used this model to construct a semi-analytical solution based on an idealized cylindrical tube model, as well as numerical solutions based on a truncated ellipsoidal model and a human left ventricular model that was reconstructed from magnetic resonance images. We show that our model is able to predict key features in the end-diastolic pressure-volume relationship that were observed experimentally and clinically during ventricular growth and reverse growth. We also show that the residual stress fields generated as a result of differential growth in the cylindrical tube model are similar to those in other nonidentical models utilizing the same geometry.

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV., (© 2022. The Author(s).)

Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics; however, many existing FE models are phenomenological and thus do not capture cellular-level mechanics. This work implements a cellular-level contraction scheme into an existing nonlinear FE code to model ventricular contraction. Specifically, this contraction model incorporates three myosin states: OFF-, ON-, and an attached force-generating state. It has been speculated that force-dependent transitions from the OFF- to ON-state may contribute to length-dependent activation at the cellular level. The current work investigates the contribution of force-dependent recruitment out of the OFF-state to ventricular-level function, specifically the Frank-Starling relationship, as seen through the end-systolic pressure-volume relationship (ESPVR). Five FE models were constructed using geometries of rat left ventricles obtained via cardiac magnetic resonance imaging. FE simulations were conducted to optimize parameters for the cellular contraction model such that the differences between FE predicted ventricular pressures for the models and experimentally measured pressures were minimized. The models were further validated by comparing FE predicted end-systolic strain to experimentally measured strain. Simulations mimicking vena cava occlusion generated descending pressure volume loops from which ESPVRs were calculated. In simulations with the inclusion of the OFF-state, using a force-dependent transition to the ON-state, the ESPVR calculated was steeper than in simulations excluding the OFF-state. Furthermore, the ESPVR was also steeper when compared to models that included the OFF-state without a force-dependent transition. This suggests that the force-dependent recruitment of thick filament heads from the OFF-state at the cellular level contributes to the Frank-Starling relationship observed at the organ level.

We quantify the contribution of myocytes, collagen fibers and their interactions to the residual stress field found in the left ventricle (LV) using both experimental and theoretical methods. Ring tissue samples extracted from normal rat, male and female, LV were treated with collagenase and decellularization to isolate myocytes and collagen fibers, respectively. Opening angle tests were then performed on these samples as well as intact tissue samples containing both constituents that served as control. Our results show that the collagen fibers are the main contributor to the residual stress fields found in the LV. Specifically, opening angle measured in collagen-only samples (106.45[Formula: see text] ± 23.02[Formula: see text]) and myocytes-only samples (21.00[Formula: see text] ± 4.37[Formula: see text]) was significantly higher and lower than that of the control (57.88[Formula: see text] ± 12.29[Formula: see text]), respectively. A constrained mixture (CM) modeling framework was then used to infer these experimental results. We show that the framework cannot reproduce the opening angle found in the intact tissue with measurements made on the collagen-only and myocytes-only samples. Given that the CM framework assumes that each constituent contributes to the overall mechanics simply by their mere presence, this result suggests the existence of some myocyte-collagen mechanical interaction that cannot be ignored in the LV. We then propose an extended CM formulation that takes into account of the inter-constituent mechanical interaction in which constituents are deformed additionally when they are physically combined into a mixture. We show that the intact tissue opening angle can be recovered in this framework.

An emerging class of models has been developed in recent years to predict cardiac growth and remodeling (G&R). We recently developed a cardiac G&R constitutive model that predicts remodeling in response to elevated hemodynamics loading, and a subsequent reversal of the remodeling process when the loading is reduced. Here, we describe the integration of this G&R model to an existing strongly coupled electromechanical model of the heart. A separation of timescale between growth deformation and elastic deformation was invoked in this integrated electromechanical-growth heart model. To test our model, we applied the G&R scheme to simulate the effects of myocardial infarction in a realistic left ventricular (LV) geometry using the finite element method. We also simulate the effects of a novel therapy that is based on alteration of the infarct mechanical properties. We show that our proposed model is able to predict key features that are consistent with experiments. Specifically, we show that the presence of a non-contractile infarct leads to a dilation of the left ventricle that results in a rightward shift of the pressure volume loop. Our model also predicts that G&R is attenuated by a reduction in LV dilation when the infarct stiffness is increased.