Background: Point-of-care ultrasonography (POCUS) enables cardiac imaging at the bedside and in communities but is limited by abbreviated protocols and variation in quality. We developed and tested artificial intelligence (AI) models to automate the detection of underdiagnosed cardiomyopathies from cardiac POCUS., Methods: In a development set of 290,245 transthoracic echocardiographic videos across the Yale-New Haven Health System (YNHHS), we used augmentation approaches and a customized loss function weighted for view quality to derive a POCUS-adapted, multi-label, video-based convolutional neural network (CNN) that discriminates HCM (hypertrophic cardiomyopathy) and ATTR-CM (transthyretin amyloid cardiomyopathy) from controls without known disease. We evaluated the final model across independent, internal and external, retrospective cohorts of individuals who underwent cardiac POCUS across YNHHS and Mount Sinai Health System (MSHS) emergency departments (EDs) (2011-2024) to prioritize key views and validate the diagnostic and prognostic performance of single-view screening protocols., Findings: We identified 33,127 patients (median age 61 [IQR: 45-75] years, n=17,276 [52·2%] female) at YNHHS and 5,624 (57 [IQR: 39-71] years, n=1,953 [34·7%] female) at MSHS with 78,054 and 13,796 eligible cardiac POCUS videos, respectively. An AI-enabled single-view screening approach successfully discriminated HCM (AUROC of 0·90 [YNHHS] & 0·89 [MSHS]) and ATTR-CM (YNHHS: AUROC of 0·92 [YNHHS] & 0·99 [MSHS]). In YNHHS, 40 (58·0%) HCM and 23 (47·9%) ATTR-CM cases had a positive screen at median of 2·1 [IQR: 0·9-4·5] and 1·9 [IQR: 1·0-3·4] years before clinical diagnosis. Moreover, among 24,448 participants without known cardiomyopathy followed over 2·2 [IQR: 1·1-5·8] years, AI-POCUS probabilities in the highest (vs lowest) quintile for HCM and ATTR-CM conferred a 15% (adj.HR 1·15 [95%CI: 1·02-1·29]) and 39% (adj.HR 1·39 [95%CI: 1·22-1·59]) higher age- and sex-adjusted mortality risk, respectively., Interpretation: We developed and validated an AI framework that enables scalable, opportunistic screening of treatable cardiomyopathies wherever POCUS is used., Funding: National Heart, Lung and Blood Institute, Doris Duke Charitable Foundation, BridgeBio., Competing Interests: R.K. is an Associate Editor of JAMA and receives research support, through Yale, from the Blavatnik Foundation, Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. He is a coinventor of Pending Patent Applications WO2023230345A1, US20220336048A1, 63/346,610, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335, and a co-founder of Ensight-AI, Inc and Evidence2Health, LLC. E.K.O. is a co-founder of Evidence2Health LLC, and has been a consultant for Ensight-AI, Inc, and Caristo Diagnostics, Ltd. He is a co-inventor of patent applications (US17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, 63/562,335, WO2018078395A1, WO2020058713A1) and has received royalty fees from technology licensed through the University of Oxford, outside the submitted work. H.M.K. works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of Hugo Health, a personal health information platform, and co-founder of Refactor Health, a healthcare AI-augmented data management company, and Ensight-AI, Inc. All other authors declare no competing interests.