Mechanisms and efficacy of biventricular pacemakers in patients with heart failure with preserved ejection fraction

Lodge, Freya 2024. Mechanisms and efficacy of biventricular pacemakers in patients with heart failure with preserved ejection fraction. MD Thesis, Cardiff University. Item availability restricted.

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Abstract

Heart failure with preserved ejection fraction (HFPEF) is a disease with increasing prevalencelinked to ageing and to diseases of modern living, such as obesity, diabetes, atrial fibrillation and chronic kidney disease. It accounts for around half of heart failure cases. Whilst some recent treatment advances have found improved outcomes, no treatment has yet been found to improve mortality. HFPEF has traditionally been challenging to characterise due to heterogeneity of the condition and contribution from associated conditions to symptoms. However, it involves structural changes to the heart, vasculature and peripheral muscles, at a macroscopic and molecular level, that lead to exercise intolerance, breathlessness and fluid accumulation. The electrical changes in HFPEF include high prevalence of atrial fibrillation, which is both a cause and result of HFPEF, and chronotropic incompetence. However, whether atrioventricular dyssynchrony or inefficiency is a common contributor to symptoms is not known. Additionally, whilst biventricular pacemakers have been found to reduce mortality and improve symptoms in heart failure with reduced ejection fraction, with impaired heart pump function, such devices have not been investigated in HFPEF despite evidence of underlying electrical dyssynchrony in many subjects. This work investigates the role of atrioventricular conduction in the pathophysiology of HFPEF by characterising normal and abnormal conduction in aged subjects through the PR70 study and its comparison to HFPEF subjects recruited through the MEDIA-DHF study. Secondly, it describes a mechanistic study, PREFECTUS, which examines the use of biventricular pacemakers in HFPEF subjects and whether such devices could form the basis of further studies and potential treatments in this condition. Finally, this thesis will consider the findings from the two studies above in the context of available literature to provide an enhanced model of the pathogenesis of HFPEF, incorporating lifestyle, environmental, inflammatory and systemic risk factors.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Medicine
Date of First Compliant Deposit:	25 March 2025
Last Modified:	25 Mar 2025 17:13
URI:	https://orca.cardiff.ac.uk/id/eprint/177142

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