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Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy.Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness >16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II (P<0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304; P=0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854; P=0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient (R2=0.83, P<0.001); its independent determinants were left ventricular end-systolic volume (P=0.0183), indexed total ML area (P=0.0108), inter-PM distance (P=0.0378), annular height (P=0.0047), and LVOT hypertrophy index (P=0.0098).Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM–mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention.