This study sought to evaluate the incremental value of the time interval between the onset of early transmitral flow velocity (E) and the onset of early diastolic velocity (E') of the mitral annulus for the prediction of left ventricular (LV) end-diastolic pressure (EDP) in the presence of a "gray zone" value for E/E'. An E/E' ratio of 8 to 15 is classified as the "gray zone" for the estimation of LVEDP. Recently, it was suggested that prolongation of the time interval between the onset of E and E' (T(E'-E)) might indicate elevated filling pressure. Simultaneous left-sided cardiac catheterization and Doppler echocardiography were performed in 74 patients with normal systolic function. T(E'-E) was calculated as the time interval between the peak of the R wave and the onset of E' and between the peak of the R wave and the onset of E. Of the 74 patients enrolled, 55 (27 men, mean age 59 years) who had E/E' ratios of 8 to 15 were analyzed. LVEDP was elevated (>18 mm Hg) in 34 patients (62%). There was no significant difference in Doppler echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels between those with normal and high LVEDP, except T(E'-E), which was significantly longer in the latter (19.0 +/- 17.8 vs 35.0 +/- 17.0 ms, p = 0.002). The receiver-operating characteristic curves for the prediction of high LVEDP showed the largest area under the curve (0.760) for T(E'-E). In multivariate analysis, T(E'-E) added significant information to the other parameters in the prediction of high LVEDP (p = 0.029). In conclusion, T(E'-E) may have an incremental value in the estimation of LVEDP in patients with normal systolic function and indeterminate E/E' ratios.