Background: Mitral inflow filling pattern usually consists of 2 forward flow velocities in sinus rhythm: early rapid filling (E) and late filling with atrial contraction (A). However, additional mid-diastolic flow velocity (Em) may be present resulting in triphasic mitral inflow filling pattern. This study explored underlying mechanisms and clinical implications of triphasic mitral inflow velocity using tissue Doppler imaging (TDI) and plasma proBNP. Methods and Results: Of 3,024 patients who underwent transthoracic echocardiography from March to May 2003, 48 (1.6%) patients (18 male; mean age, 65짹9 years) with a triphasic mitral inflow velocity pattern, including mid-diastolic flow velocity of at least 0.2 m/s, and sinus rhythm were prospectively identified. Peak velocity of E, Em, and A, and deceleration time (DT) of the E wave velocity were measured. Diastolic mitral annular velocities were measured at the septal corner of the mitral annulus by TDI from the apical 4-chamber view. ProBNP was measured at the time of echocardiogram using Elecsys proBNP (Roche), a quantitative electrochemiluminescence immunoassay. Mean heart rate was 53짹6 beats/min (range, 43-66). Mean left ventricular (LV) ejection fraction (EF) was 65짹10% and LV systolic dysfunction (EF < 40%) was present in only 1 (2%). Patients were classified into 2 groups: group 1 (n=19) included those had mid-diastolic mitral annular velocity (E���m) and group 2 (n=29) included those without E���m. Group 1 patients had significantly higher E/A (1.6짹0.9 vs 1.2짹0.3, p=.02), Em (37짹11 vs 25짹7 cm/s, p<.0001), E/E��� (19짹6 vs 14짹5, p=.002), and left atrial volume index (41짹12 vs 31짹10 ml/m2, p=.015). E��� (4.7짹1.2 vs 6.2짹2.2 cm/s, p=.009) and A��� (6.1짹1.9 vs 8.6짹3.6 cm/s, p=.003) were significantly lower in group 1 compared with that of group 2. ProBNP was significantly higher in group 1 (1190짹1794 vs 314짹879 pmol/l, p=0.029) and it was above normal in all group 1 patients. Conclusion: The presence of E���m in subjects with triphasic mitral inflow filling pattern with mid-diastolic flow is associated with higher E/A, E/E���, elevated proBNP and enlarged left atrium indicating advanced diastolic dysfunction with elevated filling pressures.