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Background: We aimed to assess in a prospective multicenter study the quality of echocardiographic exams performed by inexperienced users guided by a new artificial intelligence software and evaluate their suitability for diagnostic interpretation of basic cardiac pathology and quantitative analysis of cardiac chamber and function., Methods: The software (UltraSight, Ltd) was embedded into a handheld imaging device (Lumify; Philips). Six nurses and 3 medical residents, who underwent minimal training, scanned 240 patients (61±16 years; 63% with cardiac pathology) in 10 standard views. All patients were also scanned by expert sonographers using the same device without artificial intelligence guidance. Studies were reviewed by 5 certified echocardiographers blinded to the imager's identity, who evaluated the ability to assess left and right ventricular size and function, pericardial effusion, valve morphology, and left atrial and inferior vena cava sizes. Finally, apical 4-chamber images of adequate quality, acquired by novices and sonographers in 100 patients, were analyzed to measure left ventricular volumes, ejection fraction, and global longitudinal strain by an expert reader using conventional methodology. Measurements were compared between novices' and experts' images., Results: Of the 240 studies acquired by novices, 99.2%, 99.6%, 92.9%, and 100% had sufficient quality to assess left ventricular size and function, right ventricular size, and pericardial effusion, respectively. Valve morphology, right ventricular function, and left atrial and inferior vena cava size were visualized in 67% to 98% exams. Images obtained by novices and sonographers yielded concordant diagnostic interpretation in 83% to 96% studies. Quantitative analysis was feasible in 83% images acquired by novices and resulted in high correlations (r≥0.74) and small biases, compared with those obtained by sonographers., Conclusions: After minimal training with the real-time guidance software, novice users can acquire images of diagnostic quality approaching that of expert sonographers in most patients. This technology may increase adoption and improve accuracy of point-of-care cardiac ultrasound., Competing Interests: Disclosures In addition to employment relationships between several authors (Dr Spiegelstein, Dr Avisar, Dr Ludomirsky, and I. Kezurer) and UltraSight, Ltd, Drs Lang, Khandheria, and Klempfner received research grants and Drs Mor-Avi, Mazursky, Handel, Peleg, and Avraham served as consultants for work related to this study. The other authors report no conflicts.