In all conditions altering wall stress and mechanical stretching, LV performance becomes insufficient at the distance, due to a number of structural and functional alterations ultimately impairing pump function, but not invariably due to reduced inotropic state. Among them, structural alteration of the normal myocardial architectures might play a key role to explain the early events of cardiac dysfunction. Abnormalities of the collagen scaffold facilitate alteration of the physiological orientation of muscular fibers and consequent impaired transmission of the contraction force through the myocardial wall toward the endocardium. Further adaptations are promoted by neurohormonal activation eventually yielding abnormal gene expression of contractile proteins. In the alterations of normal myocardial architecture, the turnover of ECM and the architecture of the scaffold is possibly as important as the organization of the cardiomyocyte layers which contributes with their normal orientation to the developed strength at the chamber level.