Grant: Doctoral: Vanier Canada Graduate Scholarships

Heart failure (HF) is a deadly condition that currently affects nearly 600 000 Canadians and represents the final pathway for myriad diseases that affect the heart. Elevated sympathetic nervous system (SNS) activity and activation of the renin-angiotensin-aldosterone system (RAAS) plays an important pathophysiologic role in the development and progression of left-sided HF. Drugs that target this neurohormonal activation are now the cornerstone in management for patients with left ventricular systolic dysfunction. Unfortunately, therapeutic progress has stood still for the management of chronic right-sided HF. This is despite the fact that right ventricle (RV) function is a key marker of prognosis across many cohorts of cardiovascular disease states, including left HF. Management still remains supportive and symptom-based, and there are no therapies which directly and selectively target the RV. Recent evidence indicates that SNS and RAAS activation are similarly involved in right HF. This suggests that therapies that selectively target either the overactivation of the SNS or RAAS may also benefit patients with right HF. The aims of this project are to explore the pathogenic neurohormonal mechanisms contributing to right HF and, given this insight, explore therapeutic strategies which target this adverse profile. The studies in this proposal are a crucial first step in exploring the development of targeted treatment strategies for the management of right HF, potentially shifting the paradigm of right HF management from supportive care alone to targeted therapies that can work mechanistically on a failing RV to improve patient outcomes.