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Purpose: The aim of this study was to evaluate the accuracy of a 3D-4D quantification of left ventricular (LV) volumes and ejection fraction (EF) using a feature tracking echocardiographic software and related post-processing tools.Methods: 20 subjects were enrolled in this study; of these 10 healthy subjects (5 male, 32±4 years), and 10 patients (4 male, 66±17years) with heart diseases (2 with dilated cardiomyopathy, 3 previous myocardial infarction, and 5 patients with hypertrophic cardiomyopathy), underwent to 2D conventional echocardiography (Simpson method), XStrain 4D (XS4D) analysis and to cardiac magnetic resonance (MRI), in the same day and in random order to quantify end diastolic volume (EDV, ml), end systolic volume (ESV, ml) and EF (%). The Simpson method was determined from four- and two-chamber (Ch) views. XS4D is a software solution merging Esaote's XStrain 2D tracking technologies with Tomtec's 3D/4D rendering. Starting from standard apical 4Ch, apical 2Ch and apical long axis heart's views elaborated with 2D Strain, XS4D provides temporal compensation of the heart rate variation, spatial alignment of the 3 views in 3D space and adaptation of a dynamic LV surface. Using well proven numerical methods XS4Dprovides various derives dynamic measurements among which global and regionalvolumes curves (including EDV,ESV and EF). The MRI quantification of LV volumes and EF included 9-13 short axis views (thickness 8 mm, gap interslice 0 mm). MRI was used as the gold standard method.Results: LV volumes obtained by XS4D (EDV:92±43 ml, ESV: 49±31 ml) and Simpson method (EDV: 82±39 ml, ESV: 35±29 ml) were significant underestimated (P<0.001) in comparison with MRI (EDV:159±54ml, ESV: 76± 45 ml). No significant difference regarding EF was found among XS4D (54±12%), Simpson method (61±13%) and MRI (56±11%). Bland-Altman analysis between XS4D and cardiac MRI showed a low level of agreement for EDV (mean difference=66.6; SD=32) and for ESV (mean difference= 31.6; SD=23); similarly Simpson method and MRI showed a low level of agreement for EDV (mean difference= 76.5; SD=30) and for ESV (mean difference= 31.6; SD=23); On the contrary, a very low bias (mean difference 2.2; SD=9.7) was found between XS4D and cardiac MRI for the quantification of EF, and between Simpson method and MRI (mean difference -4.6; SD=7.4).Conclusion. Quantification of LV volumes using XS4D allows an accurate, and reliable assessment of LV EF and arough estimation of LV volumes compared with cardiac MRI. XS4D provides volumetric data that are similar to those computed using Simpson Biplane.