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Objectives: The aim of this study was to examine the value of native and post-contrast T1 relaxation in the differentiation between healthy and diffusely diseased myocardium in 2 model conditions, hypertrophic cardiomyopathy and nonischemic dilated cardiomyopathy. Background: T1 mapping has been proposed as potentially valuable in the quantitative assessment of diffuse myocardial fibrosis, but no studies to date have systematically evaluated its role in the differentiation of healthy myocardium from diffuse disease in a clinical setting. Methods: Consecutive subjects undergoing routine clinical cardiac magnetic resonance at King''s College London were invited to participate in this study. Groups were based on cardiac magnetic resonance findings and consisted of subjects with known hypertrophic cardiomyopathy (n = 25) and nonischemic dilated cardiomyopathy (n = 27). Thirty normotensive subjects with low pre-test likelihood of cardiomyopathy, not taking any regular medications and with normal cardiac magnetic resonance findings including normal left ventricular mass indexes, served as controls. Single equatorial short-axis slice T1 mapping was performed using a 3-T scanner before and at 10, 20, and 30 minutes after the administration of 0.2 mmol/kg of gadobutrol. T1 values were quantified within the septal myocardium (T1native), and extracellular volume fractions (ECV) were calculated. Results: T1native was significantly longer in patients with cardiomyopathy compared with control subjects (p < 0.01). Conversely, post-contrast T1 values were significantly shorter in patients with cardiomyopathy at all time points (p < 0.01). ECV was significantly higher in patients with cardiomyopathy compared with controls at all time points (p < 0.01). Multivariate binary logistic regression revealed that T1native could differentiate between healthy and diseased myocardium with sensitivity of 100%, specificity of 96%, and diagnostic accuracy of 98% (area under the curve 0.99; 95% confidence interval: 0.96 to 1.00; p < 0.001), whereas post-contrast T1 values and ECV showed lower discriminatory performance. Conclusions: This study demonstrates that native and post-contrast T1 values provide indexes with high diagnostic accuracy for the discrimination of normal and diffusely diseased myocardium. [Copyright &y& Elsevier]