Why SIT Works: Normal Function Despite Typical Myofiber Pattern in Situs Inversus Totalis (SIT) Hearts Derived by Shear-induced Myofiber 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. Author Summary: Deciphering the structure-function relation in healthy hearts is important to understand cardiac pathologies. In the structure-function relation, the myofiber orientation patterns play a central role. Between people with normal organ arrangement (Situs Solitus, SS) this pattern is strikingly similar. Such consistency in myocardial structure might be the result of an adaptation process to accommodate for homogeneous distribution of myofiber strain across the wall and for optimal pump function. The heart of people with a mirror-imaged position of their organs (Situs Inversus Totalis, SIT) has a modified myofiber orientation pattern with respect to SS: normal at the LV apex, but mirrored at the base. Hence, studying SIT hearts provides a unique possibility 1) for understanding adaptation mechanisms related to myofiber orientation and mechanical load, and 2) to gain additional insights into the structure-function relations of the LV. Through mathematical modeling of LV mechanics, we have found that myofiber orientation pattern in both SS and SIT may originate from same processes of adaptive myofiber reorientation. After reorientation, pump and local myofiber function were found to be similar between SS and SIT as well: a remarkable finding when considering the large difference in myofiber orientation pattern.