The aim of this study was to demonstrate the usefulness of preload alterations in assessing left ventricular filling pressures with transmitral Doppler velocity curves. Doppler mitral inflow velocities, used to estimate left ventricular filling pressures noninvasively, are limited in predicting left ventricular filling pressures, especially in patients with normal systolic function and a "pseudonormal" mitral filling pattern. Forty-nine patients were studied in the cardiac catheterization laboratory with simultaneous Doppler echocardiography using high fidelity catheters to compare left ventricular diastolic filling pressures (pre-A wave left ventricular pressure) and Doppler mitral inflow at baseline and during reduction of preload during the strain phase of the Valsalva maneuver (n = 27) or sublingual nitroglycerin (n = 36), or both (n = 14). Doppler measurements consisted of E (initial peak velocity), A (velocity at atrial contraction), deceleration time (time from E velocity to deceleration of flow extrapolated to baseline) and absolute A wave velocity (A' [peak A wave velocity minus velocity at onset of atrial contraction]). In patients with high pre-A wave pressure (> or 15 mm Hg), there was a greater change in the E/A' ratio during the Valsalva maneuver than in patients with a normal pre-A wave pressure (-1.22 +/- 1.1 vs. -0.35 +/- 0.17; p = 0.02). A similar change was seen when comparing the change in the E/A' ratio after administration of nitroglycerin in patients with a high versus a normal pre-A wave pressure (0.81 +/- 0.49 vs. 0.18 +/- 0.17; p < 0.001). These differences were present in patients with a normal E/A ratio at baseline. Alterations in preload during assessment of Doppler echocardiographic indexes may be useful in noninvasively assessing left ventricular filling pressures.