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Deep learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from three centers. The impact of three ultrasound machines and three phenotypes of heart diseases on the automatic LVEF measurement was evaluated. Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS data set (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (P = 0.008). DPS-Net was associated with high correlations and good agreements for the LVEF measurement. High diagnostic performance was obtained that the area under receiver operator characteristic curve was 0.974, 0.948, 0.968, and 0.972 for normal hearts and disease phenotypes including atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, respectively. High performance was obtained by using DPS-Net in LV detection and LVEF measurement for heart failure with several phenotypes. High performance was observed in a large-scale dataset, suggesting that the DPS-Net was highly adaptive across different echocardiographic systems. [ABSTRACT FROM AUTHOR]