Physical activity and cardiorespiratory fitness in atrial fibrillation incidence, prognosis and patophysiology

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its burden is rapidly growing worldwide as a consequence of the ageing population and uncontrolled cardiovascular risk factors. The present thesis presents original work addressing multiple aspects of the relationship between AF, physical activity (PA) and cardiorespiratory fitness (CRF). While PA is an essential component in the management of cardiovascular risk, its role in AF risk prevention is less clear. Recently published data has emerged from large cohorts to clarify this relationship. Chapter 2 systematically reviews the literature and pools AF risk estimates with self-reported PA as the exposure variable. We found an overall AF risk reduction with higher PA with important gender differences. We also observed a non-linear dose-response relationship between PA and AF risk. Multiple studies demonstrate that obesity results in electrical and structural remodelling ultimately leading to initiation and maintenance of AF. Recent studies have suggested that this association may be mediated by lean mass. Chapter 3 analyses the relationship between AF, ventricular arrhythmias and bradyarrhythmia risk and both lean and fat mass in the UK Biobank cohort. Significant risk of AF was associated with higher lean and fat mass in both men and women. Higher fat mass was associated with higher bradyarrhythmia risk in both men and women with only men having a higher risk with higher lean mass but not women. Furthermore, significant risk of ventricular arrhythmias was associated with higher lean and fat mass with no sex interaction. Importantly, PA did not modify the risk associated with these anthropometric measurements and any of these outcomes. Patients with established AF have a higher mortality compared with no AF. Chapter 4 shows the associations between weekly total and vigorous PA dose and both all-cause and cardiovascular mortality among participants of the UK Biobank with established AF at enrolment. Total PA was associated with lower all-cause mortality in women, but not men, although the association between vigorous PA and all-cause mortality persisted across the entire cohort. Total PA was no associated with lower cardiovascular mortality while lower cardiovascular mortality was observed with up to 2000 Metabolic equivalents of task (MET)- minutes/week of vigorous PA. AF is associated with a profound electrical remodelling of the left atrium (LA) with includes reduced LA voltage, conduction abnormalities and electrogram fractionation. Chapter 5 compares total and regional LA electroanatomical characteristics across CRF levels among patients undergoing AF catheter ablation. Significantly lower voltages were found among those in the lowest CRF category, particularly in the posterior wall, with higher global and regional electrogram fractionation. LA remodelling is not only limited to electrical but also structural remodelling. LA strain (LAS) is a novel echocardiographic parameter which allows LA mechanical function. Chapter 6 looks at LAS in relation to CRF among patients with a history of AF in sinus rhythm referred for a treadmill test. We found lower LAS (reservoir, booster and conduit) as well as higher LA stiffness in association with lower CRF. Importantly, we found no differences among normal, overweight and obese.