Ventricular and Pulmonary Vascular Reserve after the Fontan Operation

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PROJECT SUMMARY CANDIDATE: Dr. Egbe's long-term goal is to become an independent clinical investigator in the field of adult congenital heart disease. His short-term goal is to study new and unexplored aspects of hemodynamics and clinical outcomes in people with Fontan palliation. To achieve these goals, Dr. Egbe plans to: (1) Acquire expertise in advanced statistical methodology, exercise physiology and hemodynamics, and management of circulatory failure in people with Fontan physiology; (2) Develop new collaborative relationships with other researchers; (3) Submit RO1 proposals during the 3rd and 5th years of the award. ENVIRONMENT: The Mayo Clinic is a world-renowned center for innovation and research, and the Adult Congenital Heart Disease program at Mayo Clinic cares for the largest cohort of Fontan patients in North America, making it ideal for patient recruitment for the proposed studies. Dr. Borlaug, the primary mentor for this grant, is an expert in exercise hemodynamics and cardiovascular physiology, and has a track record of successful mentorship. RESEARCH Background: Patients with Fontan palliation have significantly reduced long-term survival because of Fontan associated diseases (FAD). Available data suggest that FAD are downstream complications of chronic venous congestion, but there is paucity of data about the upstream hemodynamic processes, such as pulmonary vascular disease (PVD) and ventricular diastolic dysfunction (VDD), responsible for chronic venous congestion and FAD. We will address these gaps in knowledge through the proposed studies. Specific Aims: We will determine the prevalence of PVD and VDD in patients with Fontan physiology using invasive and noninvasive hemodynamic cardiopulmonary exercise testing (Aims #1 and #2), and then evaluate the impact of rest-exercise PVD and VDD on clinical outcomes (Aim #3). Study Design and Outcome Measures: The studies will be conducted on adult Fontan patients undergoing cardiac catheterization for clinical indications at Mayo Clinic Rochester, MN. Simultaneous cardiac catheterization and echocardiography will be performed at rest and during exercise (Aims #1 and #2), and the occurrence of rest-exercise PVD and VDD will be correlated with clinical outcomes during follow-up (Aim#3). Potential Public Health Contribution: Identifying and treating the early stages of PVD and VDD will potentially prevent or at least deter FAD, improve survival and reduce healthcare cost in this population. Relationship to the Career Goals of the Candidate: The data and skill set acquired during these projects will form the basis for an RO1 application focused on modifying the natural history of FAD, a critical step towards becoming an independent clinical investigator in this field.