Atrial fibroblast activity and atrial fibrillation

Abstract Introduction Atrial fibrosis is a key factor in the development of atrial fibrillation (AF)(1). 68Gallium-labelled fibroblast activation protein inhibitor (68Ga-FAPI) binds to activated fibroblasts, enabling the tracking of fibroblast activation and fibrosis activity (2). Methods Participants with heart failure with preserved ejection fraction (HFPEF), aortic stenosis (AS) and healthy volunteers underwent 68Ga-FAPI PET, cardiac magnetic resonance (CMR) imaging and echocardiography. 2 analysers were blinded to the AF status of the participants. Regions with increased visual PET uptake were identified in the atria, their position recorded and the intensity of 68Ga-FAPI activity quantified. When no regions of increased activity were identified regions of interest were drawn in the atrial septum. Maximum standardised uptake values (SUVmax) were recorded and maximum tissue-to-background ratios (TBRmax) were calculated. Results In this initial analysis of an ongoing study, 40 (28 with aortic stenosis, 8 with heart failure with preserved ejection fraction and 3 healthy volunteers) participants underwent 68Ga-FAPI PET imaging. 11 participants had AF (2 paroxysmal, 9 persistent). A total of 47 regions of increased visual uptake were identified. All participants with AF demonstrated increased visual 68Ga-FAPI PET in the cardiac atria, which commonly localised to the left atrial wall and the point of insertion of the pulmonary veins into the left atrium. 14 (48.3%) participants without AF demonstrated increased 68Ga-FAPI uptake in their atria. Upon quantification participants with AF had increased 68Ga-FAPI uptake in their atria, with higher SUVmax 2.30 (0.39) in AF vs 1.86 (SD 0.35) without; p0.05 and TBRmax values 1.58 (SD 0.23) in AF vs 1.39 (SD 0.32) without; p0.05 (Figure 1). In participants without AF, the TBRmax of regions of interest drawn in the atrial septum correlated moderately with left atrial diameter (r=0.50, p= 0.01) on echocardiography Conclusion Participants with atrial fibrillation have increased 68Ga-FAPI activity in their cardia atria compared with participants without AF. This technique holds major promise in improving our understanding of fibrosis activity in the pathogenesis of atrial fibrillation.Figure 1