OBJECTIVES: The aim of this study was to investigate the association between resting myocardial function as assessed by tissue Doppler myocardial velocities and the propensity to develop mental stress-induced ischemia (MSIMI). BACKGROUND: Tissue Doppler myocardial velocities detect preclinical cardiac dysfunction and clinical outcomes in a range of conditions. However, little is known about the interrelationship between myocardial velocities and the propensity to develop MSIMI compared with exercise stress-induced myocardial ischemia. METHODS: Resting annular myocardial tissue Doppler velocities were obtained in 225 patients with known coronary heart disease who were subjected to both conventional exercise stress testing as well as a battery of 3 mental stress tests. Diastolic early (e') and late (a') as well as systolic (s') velocities were obtained, and the eas index, an integrated measure of myocardial velocities, was calculated as e'/(a' × s'). MSIMI was defined as: 1) the development or worsening of regional wall motion abnormality; 2) a reduction in left ventricular ejection fraction ≥ 8%; and/or 3) ischemic ST-segment changes during 1 or more of the 3 mental stress tests. RESULTS: A total of 98 of 225 patients (43.7%) exhibited MSIMI. Patients developing MSIMI had significantly lower s' (7.0 ± 1.7 vs. 7.5 ± 1.2, p = 0.016) and a' (8.9 ± 1.8 vs. 10.0 ± 1.9, p < 0.001) at baseline, whereas e' did not differ (6.5 ± 1.7 vs. 6.5 ± 1.8, p = 0.85). Furthermore, the eas index was significantly higher (0.11 ± 0.04 vs. 0.09 ± 0.03, p < 0.0001). The eas index remained significantly associated with the propensity to develop MSIMI (odds ratio per 0.05-U increase: 1.85; 95% confidence interval: 1.21 to 2.82; p = 0.004) after adjustment for resting left ventricular ejection fraction, resting wall motion index score, sex, and social circumstances of living. There was no association between resting eas index and exercise stress-induced myocardial ischemia. CONCLUSIONS: MSIMI but not exercise stress-induced myocardial ischemia is independently associated with resting abnormalities in myocardial systolic and late diastolic velocities as well as the integrated measure of the eas index in patients with known coronary artery disease. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).