Abstract Body (Do not enter title and authors here): Introduction. Myocardial infarction (MI) leads to cardiac myocyte death and scarring, resulting in significant biomechanical remodeling of the left ventricle (LV). Maladaptive LV remodeling post-MI is known to contribute to the development of heart failure (HF). Understanding the role of LV free wall (LVFW) biomechanical remodeling in the transition of infarcted hearts to HF will improve prognostic capabilities and intervention strategies. Our objective in this study was to assess the association between LVFW anisotropic stiffening and organ-level functional adaptations.

Methods. MI was induced in WKY rats via the ligation of the LAD artery, and transthoracic echocardiography was performed to measure ejection fraction (EF). Fresh LVFW myocardial samples were harvested and subjected to biaxial tensile loading hearts were harvested at five timepoints: sham, and weekly from 1wk to 4wk post-MI (n=6 for each timepoint). The samples were stretched to 30% along the circumferential and longitudinal directions, and stiffness (slope of stress-stretch curves at 30% stretch) in each direction was measured. The ratio between longitudinal and circumferential stiffnesses was defined as the LVFW anisotropy.

Results. EF reduced post-MI (Fig. 1A), and pre- and post-MI changes in EF (denoted by ΔEF) showed a significant reduction at later timepoints (Fig. 1B). Although circumferential stiffness remained unchanged with time (Fig. 1C), longitudinal stiffness tended to increase post-MI, thus altering the overall anisotropy of LVFW tissues (Fig. 1C). The correlation between the anisotropy and EF indicated that an increased longitudinal bias post-MI was strongly correlated with reduced EF and LV decompensation (Fig. 1D).

Conclusions. Our results suggest that the myocardium stiffness changes anisotropically with a bias in the longitudinal direction post-MI. The strong correlation between myocardial anisotropy and EF suggests that studying alterations in LVFW biomechanical markers and their relationships with deteriorations in LV function could provide insights into the mechanisms of transition to HF post-MI. The quantification of these markers through cardiac imaging offers to improve early prognostication of HF post-MI.