The aim of this study was to determine whether severe mitral regurgitation (MR) is progressive and whether tissue-Doppler (TD)-derived indexes can detect early left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of mitral valve chordae was performed in pigs (n = 8). Before MR (baseline), immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was assessed using conventional and TD-derived indexes. The severity of MR was quantified using regurgitant fraction and effective regurgitant orifice area (EROA). In all animals, MR was severe. On follow-up, the LV dilated progressively over time, but LV ejection fraction did not decrease. With the increase in LV dimensions, the forward stroke volume remained unchanged, but the mitral annular dimensions, EROA, and regurgitant fraction increased (EROA = 41 +/- 2 and 51 +/- 2 mm(2) post-MR and at 3 mo, respectively, P < 0.01). Peak systolic myocardial velocities, strain, and strain rate increased acutely post-MR and remained elevated at 1 mo but declined by 3 mo (anterior strain rate = 2.9 +/- 0.1 and 2.4 +/- 0.2 s(-1) post-MR and at 3 mo, respectively, P < 0.001). Therefore, in a chronic model of MR, serial echocardiography demonstrated that MR begets MR and that those TD-derived indexes that initially increased post-MR decreased to baseline before any changes in LV ejection fraction.