Tissue Doppler indexes of left ventricular (LV) filling pressure are prone to angulation errors and tethering and are less reliable in patients with preserved LV ejection fraction and indeterminate early peak transmitral diastolic flow (E)/mitral early diastolic velocity (Ea) (8 <E/Ea <15). Two-dimensional echocardiographic global longitudinal diastolic strain (Ds) and strain rate (DSr) were measured during peak mitral filling, and combined with E, derived new noninvasive indexes of LV filling pressure (E/Ds and E/10DSr). These indexes were compared with simultaneously invasively measured LV preatrial (pre-A) contraction pressure and E/Ea. Fifty patients were studied. Mean age was 55.9 +/- 9.9 years, 22 (43%) were women, and mean LV ejection fraction was 49.3 +/- 18.0%. Ds (R = 0.48, p <0.001) and DSr (R = 0.43, p = 0.002) correlated with invasively measured -dP/dt. Correlations between E/Ds and E/10DSr with LV pre-A pressure were R = 0.81 (p <0.001) and R = 0.80 (p <0.001) compared with R = 0.63 (p <0.001) between E/Ea and LV pre-A pressure, respectively. E/Ds > or =8 had higher sensitivity and specificity (95% and 94%, respectively; area under the curve = 0.96, p <0.0001) than E/Ea > or =15 (sensitivity 81%, specificity 75%; area under the curve = 0.85, p <0.0001) for the prediction of LV pre-A pressure > or =15 mm Hg (p = 0.01 for comparison). In patients with LV ejection fraction > or =50% and 8 <E/Ea <15, E/Ds and E/DSr were more accurate than E/Ea for determination of LV pre-A pressure. In conclusion, a novel ratio 2-dimensional echocardiographic diastolic strain ratio (E/Ds) was a better predictor of LV filling pressure than E/Ea. In patients with LV ejection fraction > or =50% or indeterminate E/Ea, both E/Ds and E/10DSr (a ratio based on global DSR) were better predictors of LV filling pressure than E/Ea.