The clinical guidelines for asymptomatic patients with chronic mitral regurgitation (MR) use the ejection fraction (EF) to trigger surgical referral. We hypothesized that the EF is not sensitive enough to detect the earliest contractile injury in chronic MR and that the injury associated with chronic MR is not global but heterogeneous, occurring regionally and predictably, before the onset of global left ventricular (LV) dysfunction.Fifteen patients with chronic MR and normal LVEF by echocardiography underwent cardiac magnetic resonance imaging with tissue tagging. Point-specific comparisons (at 15,300 LV grid points) of multiple strain parameters to a normal human strain database allowed normalization of patient-specific regional contractile function. Data were mapped over patient-specific 3-dimensional geometry and averaged across 6 LV regions.Global LV longitudinal and circumferential myocardial strains were normal for all 15 patients with MR compared with normal controls (P > .05). Despite preserved global function, the anteroseptum and posteroseptum demonstrated significantly worse contractile function compared with other LV regions (P = .003 and P = .035, respectively). Hypercontractile regions (lateral walls) appeared to compensate (P = .002) for the reduced septal contractile function, masking injury detection by global indexes.The earliest contractile injury seen in patients with MR is heterogeneous and consistently distributed along the LV septum. Compensatory responses include hypercontractility of other regions. These data suggest that rather than relying on global LV contractile metrics, which cannot detect early injury, patients might be better served by undergoing directed surveillance of “sentinel” LV regions (LV septum) with high-resolution metrics of regional contractile function.