PROJECT SUMMARY The single ventricle (SV) heart is a critical birth defect that requires several palliative surgeries for patient survival. Even when these surgeries are considered successful, SV hearts can develop heart failure (HF), resulting in just a 43% 30-years of age survival rate for patients. The SV's biomechanics underlying the progression to HF could provide critical enabling information that could help improve SV patients' outcomes and surgical planning. Despite that, SV biomechanics remain not well understood. Existing echocardiography analysis tools are designed for adult hearts and cannot accurately or reproducibly evaluate fetal and neonatal echocardiograms. Thus, currently, there are no available tools to study the biomechanics of SV hearts. Beyond this, conventional metrics such as ejection fraction (EF) fail to capture SV hearts' growth and remodeling. We previously developed a novel, automated analysis tools that can quantify ventricular biomechanics from routine B-mode and color Doppler recordings. We tested these tools using pre- and postnatal normal and hypoplastic left heart patients. We simultaneously measured conventional metrics (e.g., EF), global longitudinal strain and strain rate, interventricular pressure difference, and flow energy losses. Such measurements have never been possible using existing echocardiogram analysis tools. Our initial findings indicated these metrics differed between SV and normal postnatal hearts, with statistical significance. We propose to test the hypothesis that differences in diastolic flow, pressure, and energy-loss, correlate with pre- and post-Fontan procedure outcomes and predict progression to failure. We will aim to (i) optimize and establish the accuracy and reliability of our novel and integrated echocardiography analysis for SV hearts and subsequently use our tools to establish quantitative biomechanics and hemodynamic differences between healthy and SV hearts. Further, we aim to: (ii) analyze SV hearts using a prospective longitudinal study to develop correlations between the evolution of hemodynamics and biomechanics parameters of SV hearts with time-point outcomes, such as growth and event-free survival at fetal, neonatal, and pre- and post-Fontan stages. This project aims to improve predictions of outcomes and enable better surgical planning and clinical management for children with SV heart defects. This project's goal would be to establish our tools in clinical practice.