Why sIT works : normal function despite typical myober pattern in situs inversus totalis (SIT) hearts derived by shear-induced myrunober reorientation

The left ventricle (LV) of mammals with Situs Solitus (SS, normal organ arrangement) displays hardly any interindividual variation in myofiber pattern and experimentally determined torsion. SS LV myofiber pattern has been suggested to result from adaptive myofiber reorientation, in turn leading to efficient pump and myofiber function. Limited data from the Situs Inversus Totalis (SIT, a complete mirror image of organ anatomy and position) LV demonstrated an essential different myofiber pattern, being normal at the apex but mirrored at the base. Considerable differences in torsion patterns in between human SIT LVs even suggest variation in myofiber pattern among SIT LVs themselves. We addressed whether different myofiber patterns in the SIT LV can be predicted by adaptive myofiber reorientation and whether they yield similar pump and myofiber function as in the SS LV. With a mathematical model of LV mechanics including shear induced myofiber reorientation, we predicted myofiber patterns of one SS and three different SIT LVs. Initial conditions for SIT were based on scarce information on the helix angle. The transverse angle was set to zero. During reorientation, a non-zero transverse angle developed, pump function increased, and myofiber function increased and became more homogeneous. Three continuous SIT structures emerged with a different location of transition between normal and mirrored myofiber orientation pattern. Predicted SIT torsion patterns matched experimentally determined ones. Pump and myofiber function in SIT and SS LVs are similar, despite essential differences in myocardial structure. SS and SIT LV structure and function may originate from same processes of adaptive myofiber reorientation

Effects of activation pattern and active stress development on myocardial shear in a model with adaptive myofiber reorientation

It has been hypothesized that myofiber orientation adapts to achieve a preferred mechanical loading state in the myocardial tissue. Earlier studies tested this hypothesis in a combined model of left ventricular (LV) mechanics and remodeling of myofiber orientation in response to fiber cross-fiber shear, assuming synchronous timing of activation and uniaxial active stress development. Differences between computed and measured patterns of circumferential-radial shear strain Ecr were assumed to be caused by limitations in either the LV mechanics model or the myofiber reorientation model. Therefore, we extended the LV mechanics model with a physiological transmural and longitudinal gradient in activation pattern and with triaxial active stress development. We investigated the effects on myofiber reorientation, LV function, and deformation. The effect on the developed pattern of the transverse fiber angle at,0 and the effect on global pump function were minor. Triaxial active stress development decreased amplitudes of Ecr towards values within the experimental range and resulted in a similar base-to-apex gradient during ejection in model computed and measured Ecr. The physiological pattern of mechanical activation resulted in better agreement between computed and measured strain in myofiber direction, especially during isovolumic contraction phase and first half of ejection. In addition, remodeling was favorable for LV pump and myofiber function. In conclusion, the outcome of the combined model of LV mechanics and remodeling of myofiber orientation is found to become more physiologic by extending the mechanics model with triaxial active stress development and physiological activation pattern

Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation

In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of ∼8∘ predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work (∼18%) and in global pump work (∼17%) in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information

How to choose myofiber orientation in a biventricular finite element model?

Biventricular (BiV) finite element (FE) models of cardiac electromechanics are evolving to a state where they can assist in clinical decision making. Carefully designed patient-specific geometries are combined with generic myofiber orientation data, because of lack of accurate techniques to measure myofiber orientation. However, it remains unclear to what extent the assumption of a generic myofiber orientation influences predictions on cardiac function from BiV FE models. As an alternative approach, it was suggested to let the myofiber orientation adapt in response to fiber cross-fiber shear. The aim of this study was to investigate to what extent variations in myofiber orientation as induced by adaptive myofiber reorientation caused variations in global stroke work in a BiV FE model and whether the adaptation model could be used as an alternative approach to prescribe the myofiber orientation in these models. An average change in myofiber orientation over an angle of about 8 ∘ , predominantly in transmural direction, resulted in a 91 % increase of LV and 20 % increase of RV stroke work. These findings indicate the importance for a more thorough effort to address a realistic myofiber orientation. The currently used model for adaptive myofiber reorientation seems a useful approach to prescribe the myofiber orientations in BiV FE models