Secondary Analysis of Noninvasive Imaging Biomarkers for the Early Prediction of Single Ventricle Failure - PROJECT SUMMARY Single ventricle heart disease (SVD) is a group of potentially lethal congenital heart defects (CHDs) that affects up to 2 in every 10,000 live births in the United States [1]. Children with SVD typically undergo a series of three palliative surgeries, ultimately resulting in the Fontan circulation. Though this staged surgical strategy for treatment has increased short-term survival, experience has shown that the single ventricle is inadequate for long-term circulatory support and patients are hospitalized for many different complications [2, 3], requiring composite outcomes to adequately describe them [4]. We have recently shown that one critical component is the lack of complete understanding of the coupled systemic-pulmonary (Fontan) circulation [5, 6]. Indeed, SVD failure continues to be clinically evaluated predominantly through functional assessment of the single ventricle, with only minor additional consideration given to central venous pressure (CVP), pulmonary vascular resistance (PVR), and to many other comorbidities that often emerge as early as adolescence [7]. This evaluation paradigm also gives little to no consideration of overall vascular compliance, flow pulsatility, or to a host of other heterogeneous disease features, despite emerging recognition that such features have critical importance in overall survival. We hypothesize that parameters of vascular compliance as well as other heterogeneous features independently associate with end-organ damage and will improve prediction of composite outcome. To address this hypothesis, we will noninvasively quantify systemic and pulmonary vascular compliance through novel analysis of previously collected standard-of-care and unique research-based magnetic resonance imaging (MRI) data. With a group of new vascular compliance parameters, together with standard clinical measures, metabolomic, assay, and proteomic measures obtained from a large and highly phenotyped Fontan population, our secondary analysis goal is to develop new prognostic models for SVD patients, and in the long-term implement real time monitoring of physiologic CV parameters that may preemptively identify circulatory failure in children with SVD.
