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Purpose Assessment of systemic right ventricular (RV) function is a key point during the follow-up of patients with transposition of the great arteries (TGA). Aims of our study were to detect the systemic RV myocardial function using two-dimensional strain echocardiography (2DSE), and to evaluate the relationship between RV function and response to cardiopulmonary exercise test (CPET) in asymptomatic or minimally symptomatic patients with chronic RV overload due to TGA following the Mustard procedure or to congenitally corrected TGA.Methods: Twenty patients (9 M/11F; 28±11 years) with systemic RV (14 pts with atrial repair for TGA and 6 with congenitally corrected transposition) were studied. RV function was analyzed by conventional echocardiography and by 2DSE analysis also in 20 healthy age-comparable controls. All TGA patients underwent a bicycle symptoms-limited CPET and blood sampling for NT–pro-BNP levels determination.Results: Both the infundibulum and the inflow tract of systemic RV were dilated. Conventional parameters of longitudinal RV contraction, such as tricuspid annular plane excursion (TAPSE) were significantly reduced in TGA (12.6 ± 4.1 mm vs. 2.1 mm; p<0.01). RV global longitudinal strain (RV GLS) and regional peak myocardial RV strain were significantly impaired in patients with TGA compared with controls (9.8±3.1% vs. 21.3±2.2 % p<0.001). At CPET, mean VO2 peak in TGA was 15.5±7.7 (mean 48% of the predicted value). A significant correlation was detectable of RV GLS with VO2 peak, % predicted (r = -0.45; P < 0.0001) and Watts performed (r = -0.35; p<0.01). These correlations with RV GLS remained significant even in multivariate analysis. Conversely, no correlations were observed among TAPSE, NT–pro-BNP values and functional capacity.Conclusions: 2DSE represents a promising non-invasive technique to assess systemic RV myocardialfunction in patients with TGA. Reduced RV myocardial deformation is related to decreased ability to perform aerobic exercise and reduced work rate during CPET.