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Background: Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a key diagnostic tool in the differential diagnosis between non-ischemic cause of cardiac chest pain. Some patients are not eligible for a gadolinium contrast-enhanced CMR; in this scenario, the diagnosis remains challenging without invasive examination. Our purpose was to derive a machine learning model integrating some non-contrast CMR parameters and demographic factors to identify Takotsubo cardiomyopathy (TTC) in subjects with cardiac chest pain., Material and Methods: Three groups of patients were retrospectively studied: TTC, acute myocarditis, and healthy controls. Global and regional left ventricular longitudinal, circumferential, and radial strain (RS) analysis included were assessed. Reservoir, conduit, and booster bi-atrial functions were evaluated by tissue-tracking. Parametric mapping values were also assessed in all the patients. Five different tree-based ensemble learning algorithms were tested concerning their ability in recognizing TTC in a fully cross-validated framework., Results: The CMR-based machine learning (ML) ensemble model, by using the Extremely Randomized Trees algorithm with Elastic Net feature selection, showed a sensitivity of 92% (95% CI 78-100), specificity of 86% (95% CI 80-92) and area under the ROC of 0.94 (95% CI 0.90-0.99) in diagnosing TTC. Among non-contrast CMR parameters, the Shapley additive explanations analysis revealed that left atrial (LA) strain and strain rate were the top imaging markers in identifying TTC patients., Conclusions: Our study demonstrated that using a tree-based ensemble learning algorithm on non-contrast CMR parameters and demographic factors enables the identification of subjects with TTC with good diagnostic accuracy., Translational Outlook: Our results suggest that non-contrast CMR features can be implemented in a ML model to accurately identify TTC subjects. This model could be a valuable tool for aiding in the diagnosis of subjects with a contraindication to the contrast media. Furthermore, the left atrial conduit strain and strain rate were imaging markers that had a strong impact on TTC identification. Further prospective and longitudinal studies are needed to validate these findings and assess predictive performance in different cohorts, such as those with different ethnicities, and social backgrounds and undergoing different treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)