Mathematical models provide a suitable platform to test hypotheses on the relation between local mechanical stimuli and responses to cardiac structure and geometry. In the present model study we tested hypothesized mechanical stimuli and responses in cardiac adaptation to mechanical load on their ability to estimate a realistic myocardial structure of the normal and the situs inversus totalis (SIT) left ventricle (LV). In a cylindrical model of the left ventricle: 1) mass was adapted in response to myofiber strain at begin of ejection and global contractility (average systolic pressure); 2) cavity volume was adapted in response to fiber strain during ejection and; 3) myofiber orientations were adapted in response to myofiber strain during ejection and local misalignment between neighboring tissue parts. The model was able to generate a realistic LV geometry and structure. In addition, the model was also able to simulate the instigating situation in the rare SIT LV with opposite torsion and transmural courses in myofiber direction between the apex and the base (Delhaas et al. (2008)[5]). These results substantiate the importance of mechanical load in the formation and maintenance of cardiac structure and geometry. Furthermore, in the model, adapted myocardial architecture was found to be insensitive to fiber misalignment in transmural direction, i.e. myofiber strain during ejection was sufficient to generate a realistic transmural variation in myofiber orientation. In addition, the model estimates that despite differences in structure, global pump work and mass of the normal and the SIT LV are similar.