The purpose of the study was to assess whether quantification of myocardial involvement by Doppler tissue echocardiography (DTE) enhances the accuracy of echocardiographic characterization of cardiac amyloidosis (CA). A group of 36 patients with CA (mean age 58 +/- 13 years; 22 male) and 40 age-matched control patients were studied. Patients with CA were divided into CA-1 subgroup with nonrestrictive (n = 22) and CA-2 with restrictive left ventricular (LV) filling pattern (n = 14). Peak lateral and medial mitral annulus velocities by pulsed wave DTE were measured in systole, early diastole, and late diastole. Using color M-mode DTE of the LV posterior wall, mean myocardial velocities (MMV) and myocardial velocity gradient (MVG) were measured during ventricular ejection, early and late isovolumic relaxation (IVR), rapid ventricular filling, and atrial contraction. In both CA-1 and CA-2 groups, mitral annulus velocities, MMV, and all MVG were lower than those measured in control patients, with the exception of peak late diastolic annulus velocities at lateral side and MMV in atrial contraction. MVGs in both early IVR and rapid ventricular filling were lower in the CA-1 as compared with the CA-2 group. Late IVR-MVG was negative in control patients and positive in patients with CA indicating a faster movement of the subendocardium rather than the subepicardium during late IVR in patients with CA (0.88 +/- 0.50 s(-1) vs -0.40 +/- 1.59 s(-1); P <.001). The following parameters: peak early diastolic annulus velocities at lateral side < or = -12 cm/s, peak early diastolic annulus velocities at medial side < or = -10 cm/s, early IVR-MMV < or = -2.5 cm/s, early IVR-MVG < or = -0.7 s(-1), and late IVR-MVG > or = 0.5 s(-1) differentiated patients with CA from control patients with an overall accuracy of 0.82, 0.83, 0.81, 0.87, and 0.81, respectively. In patients with CA, reduction in early IVR-MMV was independent of patients' age and LV mass. DTE indices proved helpful in differentiating patients with CA from control patients including those patients with CA who had borderline conventional echocardiographic features and nonrestrictive LV filling pattern.