Does venous compliance influence cardiovascular physiology in HFpEF?

Heart failure is the commonest cardiovascular cause for hospital admission in people aged >65years. It has become increasingly evident that HF with preserved ejection fraction (HFpEF) is the commonest form of HF, accounting for more than 50% of all cases. Concerningly, to date, no therapy has been shown to improve survival or to consistently reduce hospitalization and quality of life. As such, HFpEF remains an area of major unmet clinical need. The pathophysiology of HFpEF is complex, with major cardiovascular elements related to increased myocardial and arterial stiffness. These features are related to ageing and concomitant hypertension. Recent theories have also focussed on the potential role of the venous circulation and its stiffness, given that venous compliance is an important contributor to the mean circulatory filling pressure. This study will investigate venous compliance in animal models and in patients. Project description: Synopsis of the project, highlighting the main features of the project including the potential research question, aim and rationale. This project is ideally suited for a BMedSci student. Part 1: Our laboratory has established models in mice designed to recapitulate features of HFpEF. These studies are performed in aging hypertensive mice and in obese mice. In this study we plan to collect the vena cavae and study the mechanical properties (stiffness) and to study the histological, cellular and molecular properties compared to healthy mice. Part 2. A study will be conducted in HFpEF patients to investigate the stiffness of veins. This will be conducted by measuring the pressure inside veins concomitantly with the diameter under various states, to construct a compliance relationship. By understanding the way in which veins remodel, and the stimuli that drive the process we hope to develop better treatments for HFpEF.