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Purpose: Dipyridamole stress echo (DSE) is currently used as an alternative to dobutamine stress echo in detecting coronary artery disease (CAD). The lower sensitivity in identifying a single-vessel CAD is a major drawback of DSE. The purpose of this study was to investigate incremental value of global longitudinal strain (GLS) to wall motion (WM) analysis for detection of single vessel CAD during DSE.Methods: 15 patients (9 men, 62±7 years), with intermediate pre-test probability of disease, underwent concomitant DSE and coronary angiography. Optimal cutoff value to define normal GLS was -20%. Diagnostic accuracy in the identification of CAD, evaluated through sensitivity, specificity and positive/negative predictive values (PPV/NPV), was analyzed for WM score index (WMSI) and GLS. Concordance between each diagnostic method and the reference standard, represented by the presence of CAD was evaluated by kappa score and Kendall's tau coefficient.Results: Prevalence of a significant CAD (more than 50% of luminal narrowing) was 77% in overall population and prevalence of single vessel CAD was 70%. The GLS significantly decreased from rest (-17±4%) to peak stress echo (–15±4%, p<0.001). Sensitivity, specificity, PPV and NPV for WMSI were respectively: 50%, 67%, 83% and 29%. However, combination GLS and WMSI had the highest sensitivity (70%), specificity (70%), PPV (87.5%) and NPV (40%). Furthermore GLS showed a higher concordance with coronary angiography (k = 0.75; Kendall's tau = 0.78) than WMSI (k = 0.11; Kendall's tau = 0.14).Conclusions: The GLS analysis had higher diagnostic accuracy than WM analysis for detection of a single vessel CAD. However, combination GLS and WMSI resulted in significant incremental increase in the accuracy of DSE, especially with regard to the test sensitivity.