We sought to examine the hemodynamic determinants and clinical application of the peak acceleration rate of early (Ea) diastolic velocity of the mitral annulus by tissue Doppler. Simultaneous LA and left ventricular (LV) catheterization and Doppler echocardiography (DE) were performed in 10 dogs. Preload was altered using volume infusion and caval occlusion, whereas myocardial lusitropic state was altered with dobutamine and esmolol. The clinical application was examined in 190 consecutive patients (control: 55, impaired relaxation: 41, pseudonormal: 46 and restrictive LV filling: 48). In addition, in 60 consecutive patients, we examined the relation between it and mean wedge pressure (PCWP) with simultaneous DE and right heart catheterization. In canine studies, a significant positive relation was present between peak Acc rate of Ea and transmitral pressure gradient only in the stages with normal or enhanced LV relaxation, but with no relation in the stages where was 50 ms. Its hemodynamic determinants were: , LV minimal pressure and transmitral pressure gradient. In clinical studies, peak Acc rate of Ea was significantly lower in patients with impaired LV relaxation irrespective of filling pressures (p<0.001), and with similar accuracy to peak Ea velocity (AUC for septal and lateral peak Acc rates: both 0.78) in identifying these patients. No significant relation was observed between peak Acc rate and PCWP. Peak acceleration rate of Ea appears to be a useful index of LV relaxation but not of filling pressures and can be applied to identify patients with impaired LV relaxation irrespective of their filling pressures.