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Few data exist on the potential utility of a cardiac point-of-care ultrasound (POCUS) examination in the outpatient setting to assist diagnosis of significant cardiac disease. Using a retrospective sequential cohort design, we sought to derive and then validate a POCUS examination for cardiac application and model its potential use for prognostication and cost-effective echo referral.For POCUS examination derivation, we reviewed 233 consecutive outpatient echo studies for 4 specific POCUS "signs" contained therein representing left ventricular systolic dysfunction, left atrial enlargement, inferior vena cava plethora, and lung apical B-lines. The corresponding formal echo reports were then queried for any significant abnormality. The optimal POCUS examination for identifying an abnormal echo was determined. We then reviewed 244 consecutive outpatient echo studies from another institution for associations between the optimal POCUS examination, clinical variables, and referral source with major adverse cardiac events and all-cause mortality in univariate and multivariate models. Assuming a referral model where the absence of POCUS signs or variables would negate initial echo referral, theoretical cost savings were expressed as a percentage in reduction of echo studies.In the derivation cohort, the combination of two signs, denoting left atrial enlargement and inferior vena cava plethora resulted in the highest accuracy of 72% [95% CI: 65%, 78%] in detecting an abnormal echocardiogram. In the validation cohort, mortality at 5.5 years was 14.6% overall, 23% in patients with the left atrial enlargement sign (OR 3.5 [1.6, 7.6]), 25% with inferior vena cava plethora sign (OR 2.2 [0.8, 6.0]), and 8.0% (OR 0.3 [0.2, 0.7]) in those lacking both signs. After adjusting for age, both diabetes (OR 4.8 [2.0, 11.6]), and the left atrial enlargement sign (OR 2.4 [1.1, 5.4]) remained independently associated with mortality (p0.05). In the referral model, patients younger than 65 years of age without diabetes and without the left atrial enlargement sign would not have received echo referral, resulting in a 33% reduction in total echo cost and would have constituted a low-risk group with a 1.2% 5.5-year mortality.A quick-look sign for left atrial enlargement is associated with 5-year mortality and could function as an easily obtained outpatient POCUS examination to help in identifying patients in need of echo referral.