Risk Factors, Mechanisms and Therapeuthic for Right Heart Failure Associated with Pulmonary Hypertension

Abstract

Right ventricular function (RV) is one of the most important predictors of prognosis in many cardiovascular disease states. Despite the significance of RV function to survival, there are no therapies that directly nor selectively improve RV function. As well, the basis for RV failure is poorly understood. This is particularly relevant for patients with pulmonary arterial hypertension (PAH), where RV failure in the setting of pressure overload is the leading cause of death. PAH will be introduced in the 2nd chapter of this thesis by comparing and refining contemporary mortality risk assessment strategies. I will then explore 1) RV neurohormonal function and, 2) RV energetics, two molecular pathways thought to be involved in the pathogenesis and progression of maladaptive RV failure. I employed small animal molecular imaging using positron emission tomography (PET) to non-invasively investigate these pathways. The PET imaging techniques employed in this thesis have the unique potential for translation to human studies, to further explore disease mechanisms.