Heart Failure with Preserved Ejection Fraction in Atrial Fibrillation

Abstract

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are two highly prevalent chronic cardiovascular conditions associated with significant morbidity and mortality. It is increasingly recognised that these two conditions are closely linked and commonly coexist. This thesis investigates the influence of HFpEF in patients with AF, exploring its prevalence, risk factors, pathophysiological mechanisms, diagnostic challenges and influence on patient symptoms and potential outcomes. A cohort of 125 patients in total, taken from 177 screened patients with AF undergoing AF ablation was used to investigate these aims. Utilising invasive haemodynamic testing, chapter 2 investigates the prevalence of HFpEF in a cohort of patients with symptomatic AF and no clinical features of heart failure. Almost three quarters of this cohort (73%) demonstrated haemodynamic features of HFpEF. HFpEF was associated with increased symptoms of AF and poorer exercise tolerance providing insight into the previously unrecognised role that HFpEF plays in patient functional capacity. In addition, HFpEF was associated structural, mechanical and electrical dysfunction of the left atrium (LA) highlighting the role of LA cardiomyopathy in linking AF and HFpEF. AF and HFpEF share several cardiovascular risk factors. In chapter 3, the role of obesity in linking AF and HFpEF is explored. The study shows that, compared to non-obese AF patients, obese patients with AF are more likely to demonstrate HFpEF with higher left ventricular filling pressures, worse symptoms and poorer quality of life. These differences are underpinned by a unique obese phenotype characterised by left atrial enlargement, increased epicardial adipose tissue and therefore increased pericardial restraint. Chapter 4 explores the role of reduced cardiorespiratory fitness (CRF) on LA myopathy in AF. The study identifies reduced CRF as an independent contributor to LA myopathy, incorporating mechanical and electrical dysfunction, and therefore highlights the influence of reduced CRF on the development of HFpEF in AF. Chapter 5 explores the non-invasive diagnosis of HFpEF in AF, which represents a significant clinical challenge. The diagnostic accuracy of two validated HFpEF scoring systems (the HFA-PEFF score and the H2FPEF score) for the non-invasive diagnosis of HFpEF in AF is evaluated. Overall diagnostic accuracy of both scoring systems was found to be only moderate compared to haemodynamic testing, highlighting both the ongoing need for invasive testing in patients with AF as well as the need for the development of novel scoring systems targeted to this specific cohort of patients. Exercise intolerance is an important feature of AF and HFpEF. Chapter 6 investigates the role that LA mechanical dysfunction plays on exercise intolerance in patients with AF. LA dysfunction was associated with reduced exercise capacity in patients presenting in both AF and SR, suggesting that HFpEF plays a role in exercise intolerance in patients with AF. Stroke and systemic thromboembolism remain the most feared complications of AF. Chapter 7 investigates the potential role that HFpEF may play in stroke risk in patients with AF. Using multimodality imaging of the left atrial appendage (LAA), this study shows that the presence of HFpEF in patients with AF is associated with reduced LAA function, suggesting that HFpEF may be a significant risk factor for stroke in patients with AF. Finally, the thesis discusses avenues for further investigation with a focus on the influence that HFpEF may play in affecting outcomes in patients with AF and exploring the potential for HFpEF to be a novel therapeutic target to improve outcomes in patients with AF.