Bicuspid aortic valves undergo excessive strain during opening: A simulation study

ObjectiveThe objective of this study was to examine the influence of the morphologic characteristics of the bicuspid aortic valve on its disease progression by comparing the motion, stress/strain distribution, and blood flow of normal and stenotic tricuspid valves using simulation models.MethodsBicuspid, stenotic tricuspid with commissural fusion or thickened leaflet, and normal aortic valves were modeled with internal blood flow. Blood flow and the motion of aortic valve leaflets were studied using fluid–structure interaction finite element analysis, and stress/strain (curvature) distributions were calculated during the cardiac cycle. To mimic disease progression, we modified the local thickness of the leaflet where the bending stress was above a threshold.ResultsTransvalvular pressure gradient was greater in the bicuspid valve compared with the stenotic tricuspid valve with a similar valvular area. The bending strain (curvature) increased in both stenotic tricuspid and bicuspid valves, but a greater increase was observed in the bicuspid valve, and this was concentrated on the midline of the fused leaflets. During disease progression analysis, severity of the stenosis increased only in the bicuspid aortic valve model in terms of valvular area and pressure gradient.ConclusionsThe characteristic morphology of the bicuspid valve creates excessive bending strain on the leaflets during ventricular ejection. Such mechanical stress may be responsible for the rapid progression of this disease

Approximation for Cooperative Interactions of a Spatially-Detailed Cardiac Sarcomere Model

We developed a novel ordinary differential equation (ODE) model, which produced results that correlated well with the Monte Carlo (MC) simulation when applied to a spatially-detailed model of the cardiac sarcomere. Configuration of the novel ODE model was based on the Ising model of myofilaments, with the “co-operative activation” effect introduced to incorporate nearest-neighbor interactions. First, a set of parameters was estimated using arbitrary Ca transient data to reproduce the combinational probability for the states of three consecutive regulatory units, using single unit probabilities for central and neighboring units in the MC simulation. The parameter set thus obtained enabled the calculation of the state transition of each unit using the ODE model with reference to the neighboring states. The present ODE model not only provided good agreement with the MC simulation results but was also capable of reproducing a wide range of experimental results under both steady-state and dynamic conditions including shortening twitch. The simulation results suggested that the nearest-neighbor interaction is a reasonable approximation of the cooperativity based on end-to-end interactions. Utilizing the modified ODE model resulted in a reduction in computational costs but maintained spatial integrity and co-operative effects, making it a powerful tool in cardiac modeling

Coupling Langevin Dynamics With Continuum Mechanics: Exposing the Role of Sarcomere Stretch Activation Mechanisms to Cardiac Function

High-performance computing approaches that combine molecular-scale and macroscale continuum mechanics have long been anticipated in various fields. Such approaches may enrich our understanding of the links between microscale molecular mechanisms and macroscopic properties in the continuum. However, there have been few successful examples to date owing to various difficulties associated with overcoming the large spatial (from 1 nm to 10 cm) and temporal (from 1 ns to 1 ms) gaps between the two scales. In this paper, we propose an efficient parallel scheme to couple a microscopic model using Langevin dynamics for a protein motor with a finite element continuum model of a beating heart. The proposed scheme allows us to use a macroscale time step that is an order of magnitude longer than the microscale time step of the Langevin model, without loss of stability or accuracy. This reduces the overhead required by the imbalanced loads of the microscale computations and the communication required when switching between scales. An example of the Langevin dynamics model that demonstrates the usefulness of the coupling approach is the molecular mechanism of the actomyosin system, in which the stretch-activation phenomenon can be successfully reproduced. This microscopic Langevin model is coupled with a macroscopic finite element ventricle model. In the numerical simulations, the Langevin dynamics model reveals that a single sarcomere can undergo spontaneous oscillation (15 Hz) accompanied by quick lengthening due to cooperative movements of the myosin molecules pulling on the common Z-line. Also, the coupled simulations using the ventricle model show that the stretch-activation mechanism contributes to the synchronization of the quick lengthening of the sarcomeres at the end of the systolic phase. By comparing the simulation results given by the molecular model with and without the stretch-activation mechanism, we see that this synchronization contributes to maintaining the systolic blood pressure by providing sufficient blood volume without slowing the diastolic process