Abstract Background Atrial fibrillation (AF) is a well-established risk factor for heart failure (HF), stroke, and left ventricular (LV) dysfunction. However, only limited longitudinal data exist regarding the impact of AF burden on left ventricular (LV) structure and function. Purpose The aim of this study was to investigate the association between AF burden and longitudinal changes in LV structure and function in an older patient population with cardiac risk factors. Methods This study was a post-hoc analysis of a randomized clinical trial, which investigated whether AF screening with implantable loop recorders (ILRs) and subsequent initiation of anticoagulation could prevent stroke in high-risk individuals. As a substudy, a group of participants had extensive transthoracic echocardiography performed at baseline and a re-examination after ILR end-of-life. We included participants with available ILR data and echocardiographic data from both baseline and follow-up. We excluded participants with ongoing AF during the baseline echocardiogram. AF episodes were adjudicated by two cardiologists and AF burden was calculated as the percentage of time spent in AF during the total ILR monitoring period. Univariable and multivariable linear regression models were used to investigate the association between AF burden and changes in echocardiographic measures. The multivariable model was adjusted for age, sex, systolic blood pressure, diabetes, smoking status, previously acute myocardial infarction, previous coronary artery bypass grafting, prevalent HF, body mass index, estimated glomerular filtration rate, number of days monitored by ILR, and the number of days between the two echocardiographic examinations. Both models included adjustment for the baseline value of the echocardiographic measure. Results The study population consisted of 640 participants with available baseline and follow-up echocardiograms. Mean age was 73.6 years (±3.4 years) and 278 (43.4%) were women. AF was documented in 188 (29.4%) participants during a median ILR monitoring period of 3.2 years (IQR 2.9-3.4 years). The mean timespan between the echocardiographic examinations was median 5.0 (IQR 4.6-5.2) years. Among participants with AF, the median AF burden was 0.098% (IQR 0.026-0.758%). Over the course of echocardiographic follow-up, mean ∆GLS was -0.59% (±3.49%), mean ∆LVEF was -1.44% (±8.5%), and mean ∆E/e’ was -1.12(±3.23) in those with AF. Increasing AF burden was significantly associated with an accelerated decline in absolute global longitudinal strain in both univariable (ß= -0.12, p=0.002) and multivariable (ß= -0.11, p=0.003) models (Table 1/Figure 1). Conclusions In an older at-risk population, AF was frequent, and increasing AF burden was found to be independently associated with an accelerated decline in LV function. These findings support AF as an independent risk factor in the development of HF.