This study investigated the optimal echocardiographic indexes to determine the most hemodynamically appropriate atrioventricular (AV) delay in cardiac resynchronization therapy (CRT) for heart failure. Doppler echocardiographic optimization of AV delay in CRT has not been correlated with invasive hemodynamic indexes. In 30 patients who underwent CRT, invasive left ventricular (LV) pressure measurements with a sensor-tipped pressure guidewire and Doppler echocardiographic examination were performed <24 hours after pacemaker implantation. Invasively, the optimal sensed AV delay was determined by LV dP/dt(max). The Doppler echocardiographic methods evaluated were the velocity-time integral (VTI) of the transmitral flow (EA VTI), diastolic filling time (EA duration), the VTI of the LV outflow tract or aorta (LV VTI), and Ritter's formula. Biventricular pacing with optimized interventricular and AV delay increased LV dP/dt(max) from 777 +/- 149 to 1,010 +/- 163 dynes/s (p<0.0001). The optimal AV delay with the EA VTI method was concordant with LV dP/dt(max) in 29 of 30 patients (r = 0.96), with EA duration in 20 of 30 patients (r= 0.83), with LV VTI in 13 patients (r = 0.54), and with Ritter's formula in none of the patients (r = 0.35). In conclusion, to obtain the optimal acute hemodynamic benefit of CRT, Doppler echocardiography is a reliable tool to optimize the AV delay compared with the invasive LV dP/dt(max). The measurement of the maximal VTI of mitral inflow is the most accurate method.