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Ischemia induced left ventricular (LV) dysfunction and regional wall motion abnormalities are the earliest signs in acute coronary syndrome. Recent publications demonstrated more advantage but less limitation in the quantification of segmental myocardial function by 2-dimensional ultrasonic strain echocardiography (2DSE) when compared with the routine visual assessment. The aim of the present study was to compare the sensitivity, specificity, and clinical utility of 2DSE with standard cardiac ultrasound (SCU) in the detection of myocardial ischemia during acute coronary syndrome. Standard LV segments were investigated in 30 patients (age 62±12 years) admitted to our clinic with ST-segment elevation myocardial infarction (STEMI, n=8) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS, n=22). Segmental longitudinal peak systolic strain, visual assessment of regional wall motion abnormalities and 12-lead electrocardiogram (ECG) were recorded, analyzed and finally compared to the results of the coronary angiography. For the segmental assignment of the coronary arterial perfusion territories, we worked out a modified model based on the proposed American Heart Association 17-segment model. Ischemia induced segmental LV dysfunction could be detected more precisely with segmental longitudinal peak systolic strain, than with the visual assessment of regional wall motion abnormalities by standard echocardiography when compared to the results of coronary angiography in both STEMI and NSTE-ACS groups (absolute deviation from coronary angiography, 2DSE vs. SCU: STEMI: 4.3±0.8 vs. 7.3±0.8, NSTE-ACS: 4.1±0.6 vs. 8.6±1.2 deviation score, mean±SEM, p<0.05). There was no significant difference between the 12-lead ECG and the 2DSE in the STEMI group, however in the NSTE-ACS group the 2DSE data were shown to be a more sensitive predictor detecting myocardial ischemia than the ECG. (2DSE vs. SCU vs. ECG, sensitivity: STEMI: 79.5% vs. 35.2% vs. 77.3%; NSTE-ACS: 81.5% vs. 41.4% vs. 27.9%. specificity: STEMI: 65.3% vs. 98.0% vs. 91.8%; NSTE-ACS: 59.8% vs. 69.0% vs. 90.8%). Territorial longitudinal peak systolic strain could significantly differentiate between total occlusion and significant stenosis without occlusion in acute coronary syndrome (-6.5±0.5% vs. -11.3±1.0% respectively, mean±SEM, p<0.05). In conclusion, 2DSE is a more sensitive and accurate method compared to standard echocardiography to detect myocardial ischemia, its extension and severity in patients with acute coronary syndrome.