Introduction: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently occur in parallel. Whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics is not known. Methods: Adults with heart failure with an LV EF greater than 50% on echocardiography were prospectively recruited as part of the DIAMOND HFpEF study (NCT03050593). Participants underwent phenotyping including a panel of 49 fibroinflammatory plasma biomarkers, echocardiography and comprehensive stress cardiac MRI (CMR). Between group comparisons were adjusted for age, sex, ethnicity, body mass index (BMI), diabetes, systolic blood pressure and estimated glomerular filtration rate (eGFR). Results: 136 participants were included: sinus rhythm (n=75) and AF (n=61). Patients with AF were older (76 vs. 70 years), less ethnically diverse (minority ethnicity 7 vs. 24%) and had a lower prevalence of diabetes (36 vs. 61%). There were no significant differences in heart rate, blood pressure, BMI, eGFR, HbA1c, E/e’ or B-type natriuretic peptide, but AF patients had higher NTproANP (7704 vs. 5749pg/mL) and shorter E deceleration time (211±60 vs. 259±78ms). On CMR, ventricular volumes, mass, stress myocardial blood flow and myocardial fibrosis were similar, but those in AF had increased atrial volume (61±30 vs. 39±15mL/m 2 ), reduced systolic function (LV EF 63±8 vs. 68±8%; global longitudinal strain 13.6±2.9 vs. 14.7±2.4%, p=0.003) but higher diastolic strain rate (0.73±0.28 vs. 0.53±0.17/s, p<0.001). Patients with AF had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP and angiopoietin-2, but lower level of interleukin-8 (p<0.05 for all; Figure 1). Conclusions: In HFpEF, AF is associated with lower systolic function but higher diastolic strain rate and a different fibroinflammatory profile compared to sinus rhythm. These findings may suggest that some patients with AF and HFpEF have a distinct endotype.