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Purpose: To evaluate differences of left ventricular (LV) global and regional longitudinal function between cardiac amyloidosis (CA) and hypertensive LV hypertrophy (LVH).Methods: 18 healthy controls (C), 14 newly diagnosed, never treated hypertensives with LVH (H-LVH) (LV mass index >95 g/m2 in women and >115 g/m2) and 21 patients with CA at presentation, matched for age, underwent standard echo-Doppler including pulsed Tissue Doppler of mitral annulus. Automated function Imaging (AFI), a software which utilizes Speckle Tracking Echocardiography (STE) by simple 2-D imaging recording (>40 fps), was also performed. Peak longitudinal strain was measured at the 18 LV segments of the 3 apical views and global longitudinal strain (GLS) calculated as the average of measurements. Strain of LV basal segments (average of 6 basal segments, BLS), middle segments (MLS) and apical segments (ALS) was also obtained.Results: The 3 groups were comparable for body mass index and heart rate whereas systolic and diastolic blood pressure (both p<0.01) were higher in H-LVH. LV mass index, relative wall thickness, ejection fraction, left atrial volume index, transmitral E/A ratio and E velocity deceleration time were similar between CA and H-LVH. The ratio between transmitral E velocity and early diastolic velocity of the mitral annulus (average of septal and lateral sites) (E/e' ratio) was higher in CA than in H-LVH (p<0.05) and C (p<0.001). GLS was marginally lower in CA than in C (p<0.05), without difference with H-LVH. ALS did not differ among the 3 groups while MLS was mildly lower in CA than in C (p<0.01) and BLS lower in CA (-11.3 ± 5.5%) than in both H-LVH (-15.3 ± 2.6%, p<0.01) and C (-18.4 ± 2.0%, p<0.0001). Among the 6 basal segments the reduction of longitudinal strain in CA involved particularly posterior wall (p<0.001 vs C, p<0.01 vs H-LVH), lateral wall (p<0.005 vs C, p<0.05 vs H-LVH) and posterior septum (p<0.005 vs C, p<0.05 vs H-LVH). In the pooled population E/e' ratio was negatively related with BLS (r = -0.38, p<0.005) but not with GLS, MLS and ALS.Conclusions: STE-derived AFI analysis allows to identify a cluster of cardiac involvement in cardiac amyloidosis at presentation. Longitudinal function of LV basal segments is early depressed and characterizes the diseases onset when ejection fraction is still normal. The impairment of BLS is associated with the degree of LV filling pressure.