Endocardial endothelial cells constitute a barrier between the circulating blood and ventricular cardiomyocytes. Although recently our group demonstrated the importance of this type of endothelial cells in excitation-secretion coupling, there is no information on whether this type of cells contributes to cardiac pathologies such as cardiac hypertrophy. Using the well-known model of human hypertrophy and heart failure, the UM-X7.1 hereditary cardiomyopathic hamster, our results showed that during the phase of necrosis and in the absence of cardiac hypertrophy, isolated endocardial endothelial cells underwent a significant increase in cell volume compared to cells isolated from age-matched normal hamsters. This increase of the volume of endocardial endothelial cells persisted during the development of cardiac hypertrophy in the hereditary cardiomyopathic hamster. These results demonstrate for the first time, that endocardial endothelial hypertrophy precedes the development of hypertrophy in hereditary cardiomyopathy and may, via its released factors, contribute to the development of cardiac hypertrophy. These results demonstrate the importance of endocardial endothelial cells in cardiac diseases such as hypertrophy. This type of cells constitutes a new target for understanding hypertrophy and heart failure.