Regional heterogeneity of contractile function was described in patients with left ventricular (LV) hypertrophy, suggesting a predominant impairment of areas with distinct hypertrophy. Heterogeneity of myocardial hypertrophy therefore may contribute to global and regional abnormalities of LV function. Here, we systematically investigated the spatial and temporal patterning of myocardial hypertrophy in response to experimental pressure overload by cardiovascular MRI. Surprisingly, we identified a specific basolateral LV segment that is frequently spared from the development of myocardial hypertrophy and promotes systolic dysfunction. Moreover, the initial LV geometry and the vascular topology seemed to limit the extent of adaptation to pressure overload.