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Non-invasive Diagnostics and Outcomes Predictors in Pediatric PAH

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Pulmonary arterial hypertension (PAH) is a fatal disease in children and adults in which pro- gressive increases in load on the right ventricle (RV) ultimately lead to heart failure and death. Current clinical assessment of the disease involves invasive collection of main pulmonary artery pressure (mPAP) and cardiac output (CO), which are then used to determine pulmonary vascular resistance (PVR), the standard disease diagnostic. PVR is believed to represent RV afterload, and thus a primary determinant of heart failure. However, recent clinical studies of PAH by our group and others have sug- gested that including pulmonary vascular stiffness (PVS) as an additional component of RV afterload yields better prediction of PAH progression than standard PAH diagnostics. Our recent animal model studies have also established that proximal vascular stiffening increases as a consequence of vascular remodeling. Combining these findings, we propose that specific measurement of conduit proximal vas- cular stiffness (PVS) - and thus proximal remodeling - represents a new measure of disease progres- sion, and thus may offer beneficial diagnostic and prognostic information to the clinic. Dr Hunter's career goal is to contribute to cardiology at the nexus vascular mechanics and the clinical and basic science tools that diagnose and measure it. Although Dr Hunter has made significant progress in understanding the general issues of importance in clinical cardiology and for pulmonary ar- terial hypertension, his proposed career plan will address his lack of formal training in the quantitative analysis of MRI, mechanical measurements for the characterization of soft tissue, and the use and in- terpretation of animal models. Finally, it will provide protected time for the maturation of his research program. The research proposed above provides the core of a five-year career development plan; he will perform the research under the mentorship of five prominent investigators with specialties comple- mentary to the research and his training needs, while completing additional formal coursework. Through this additional training and with protected time, Dr Hunter will broaden the scope of his re- search and position himself as a noteworthy independent bioengineering investigator of pulmonary vascular disease. findings
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