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Two-dimensional (2-D) speckle tracking echocardiography (STE) accurately quantifies circumferential strain (S_circ) and radial strain (S_rad) in humans and in large and small animals. This study was performed to assess sensitivity of S_circ and S_rad to left ventricular (LV) dysfunction in mouse models. We performed 2-D and M-mode echocardiography 1) in 6 mice during superficial and profound isoflurane anesthesia, 2) serially in 12 mice to monitor the development of heart failure induced by transverse aortic constriction (TAC) and in 8 corresponding control mice, and 3) in 26 mice with varying degrees of TAC-induced heart failure and 12 corresponding control mice immediately before euthanasia. Fractional shortening (FS) and LV mass were measured from standard M-mode tracings, whereas S_circ and S_rad were derived by STE. Percent fibrosis and myocyte diameters were assessed from whole heart cross …