Project Summary Surgical repair of tetralogy of Fallot (rTOF) has led to excellent long-term survival, yet rTOF survivors often experience residual and progressive right ventricular (RV) dysfunction that burden these patients with adverse cardiac events later in life. Given this growing population, there is a strong clinical need for techniques to guide patient management. CT can be used to robustly obtain global measures of function in adult rTOF patients, but regional dysfunction is not currently quantified. Strain evaluation can be limited by changes in ventricular geometry and dyssynchronous contraction, both of which are common in rTOF patients. Myocardial work (MW) – clinically measured as the ventricular pressure-strain loop area – can overcome this concern, as it is closely related to myocardial perfusion and has been shown to be more independent of loading conditions. However, ventricular pressure measurements do not capture regional heterogeneities in myocardial stress and the impact of this approximation has not been explored. Further, the clinical utility of MW to detect early RV dysfunction in rTOF patients with CT has not been established. We have recently developed MWCT, an estimate of regional MW that combines regional endocardial strain measurements from ECG-gated CT (RSCT) and RV pressure waveforms. The proposed project aims to investigate MWCT as a quantitative tool to capture regions of subclinical dysfunction in adult rTOF patients. The ability for MWCT to detect regional dysfunction will be compared to advanced MW estimates derived from finite- element models of regional endocardial stress and RSCT. This aim will establish the simple, pressure based MWCT estimate as an effective tool for characterizing regional RV performance. Further, this aim will compare FE methods and establish an approach to measure MW as the endocardial stress-strain loop area within our MWCT pipeline. Cross-sectional CT imaging will assess whether well-performing areas on MWCT agree with cardiopulmonary exercise test (CPET) findings better than strain alone. Additionally, longitudinal evaluation via functional class and CT imaging will be performed to assess whether the amount of discordant endocardium (disagreement between regional work and strain measurements) corresponds with worsening symptomatology and dysfunction respectively. This aim will demonstrate that capturing early dysfunction will improve clinical care by detecting adverse remodeling prior to global changes. The long-term goal of this proposal is to establish CT as a feasible method for evaluating regional RV function and develop robust quantitative tools for early detection of dysfunction in all rTOF survivors.