Heart Failure in Congenital Heart Disease: The role of Myocardial Fibrosis

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DESCRIPTION (provided by applicant): This proposal seeks to ensure the continued development of Dr. Craig Broberg towards becoming an independent Clinician-Scientist. Dr. Broberg has obtained sub-specialty training in adult congenital heart disease (ACHD), and cardiac MRI. He has been successful in the design, execution, and publication of clinical studies in ACHD, and seeks the resources necessary to cany this study further. The research architecture at Oregon Health and Science University is fully supportive and invested in facilitating his longterm goal of successful independent research in ACHD. Therefore, this application includes a proposed development plan, fully supported by the Division of Cardiology, consisting of protected research time, committed mentoring, completion of a Masters in Clinical Research degree, advanced echocardiographic training, participation with other labs with overlapping interests, and successful application for independent research funding. The Research Plan proposed addresses heart failure in ACHD, a common final pathway in several specific diagnostic subgroups. Though increasing in prevalence, there is little research in ACHDrelated heart failure at present. The limited data available support the hypothesis that aldosterone-mediated fibrosis is present and thus a potential therapeutic target. Using novel MRI methods to quantify diffuse myocardial fibrosis in-vivo, we aim to: 1) demonstrate fibrosis and its association with cardiovascular dysfunction in specific ACHD subgroups, 2) relate fibrosis to aldosterone and changes in collagen synthesis, and then 3) prove its role by quantifying the interval change in fibrosis after a year of spironolactone and correlating this with collagen synthesis and structural change.