Transmitral Doppler flow patterns of patients with cardiac amyloidosis evolve from an early impaired relaxation to an advanced restrictive pattern. This reflects increasing severity of diastolic dysfunction and hence left ventricular filling pressures. The duration of the pulmonary venous atrial reversal flow was recently shown to exceed that of the mitral inflow A wave in patients with left ventricular end-diastolic pressure greater than 15 mm Hg. The objective of this study was to assess the utility of this index as a measure of the severity of cardiac amyloidosis. Comprehensive transthoracic 2-dimensional and pulsed-wave Doppler echocardiograms of the pulmonary venous and transmitral flows were made of 23 patients (10 women) with biopsy-proven diagnosis of primary systemic amyloidosis and of 49 subjects as age-matched normal controls. The amyloidosis group was divided into non-restrictive and restrictive subgroups on the basis of the patients' transmitral inflow deceleration time (>150 and < or =150 ms, respectively). The durations of the pulmonary venous atrial reversal and mitral inflow A wave were measured, and the differences between the flow durations were compared with the control and published data in the nonrestrictive and restrictive groups. The mean duration of the pulmonary venous atrial reversal was significantly longer in the amyloid than the control group (P < .01). The mean duration of the mitral inflow A wave was significantly shorter in the restrictive group than both the nonrestrictive and the control groups (P < .05). The duration of the pulmonary venous atrial reversal exceeded that of the mitral inflow A wave in all patients with cardiac amyloidosis. The difference in duration between pulmonary venous atrial reversal and mitral inflow A wave was significantly greater in the amyloidosis group compared with the normal group, and this index varied significantly within the amyloid group between the abnormal relaxation and the restrictive groups. The difference in the duration between the pulmonary venous atrial reversal and the mitral inflow A wave is a reliable index of diastolic function and can be used to assess the severity of cardiac amyloidosis.