Background: While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region.

Methods: MRI-derived anatomical imaging (150 µm 3 ) and diffusion tensor imaging (600 µm 3 ) were performed in large mammalian whole hearts (human: N=5, sheep: N=5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species.

aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (microCT) imaging. Lastly, experimental aggregate cardiomyocytes orientation distribution was then compared to the usual rule-based model using EP modeling. Electrical activity was modeled with the monodomain formulation.

The RVIP at the level of the inferior septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in aggregate cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm³ ± 0.15 cm 3 . Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model.

The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal (BIS) left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region.