Background: As ECG treadmill test (ETT) based on ST segment deviations is limited due to low sensitivity and specificity, additional analysis of the high-frequency components of the QRS complex (HFQRS) are being studied for the detection of the ischemic heart disease. We sought to evaluate the feasibility and clinical usefulness of HFQRS analysis during the exercise stress echocardiography (echoCG). Methods: We evaluated 156 patients (age 58짹10, 103 men) who performed stress echoCG and either coronary angiography (n=57) or computed tomography angiography (CTA, n=99). Exclusion criteria were as follows; indeterminate CTA results, QRS duration > 120msec, significant valve disease, hypertrophic cardiomyopathy, resting wall motion abnormalities, previous cardiac surgery and insufficient exercise during test. ETT was performed using the HyperQ stress system (BSP Ltd., Tel-Aviv, Israel), which enables automatic analysis of both conventional ST-T deviations and changes of HFQRS intensity during exercise, denoted HyperQ index of ischemia (HQI). A reduction that exceeds 50% of HQI in 3 or more leads was considered indicative of stress-induced ischemia. Results: Forty-eight patients (31%) had a significant ischemic heart disease. HyperQ analysis was unavailable in 3 patients (2%) due to inadequate ECG quality. The sensitivity and specificity of HQI for diagnosis of significant stenosis were 64% and 78%, respectively. A simple diagnostic rule, based on either positive stress echoCG or HyperQ achieved higher sensitivity of 79% and comparable specificity of 75% compared with the stress echoCG with ETT (sensitivity 58% and specificity 82%). The combined model including HyperQ analysis, stress echoCG with ETT and pre-test parameters provided the best diagnostic accuracy, with area under the receiver-operating characteristics curve (AUC) of 0.88 compared with pretest score (AUC 0.73) and/or exercise echoCG with ETT (AUC 0.84). Using optimized cut-off points on the logistic model analysis, this model provided high diagnostic accuracy of 86% sensitivity and 80% specificity. Conclusions: HFQRS analysis during exercise stress echoCG might be feasible and provide additional information for the detection of significant ischemic heart disease.