ABSTRACT NUMBER: ESOC2026LB206 LB206 - SUBOPTIMAL LAA OPACIFICATION: A NOVEL FUNCTIONAL BIOMARKER OF STROKE RISK IN AF AND ESUS – RESULTS FROM PHASE-III DAYLIGHT TRIAL AND PHASE-IV BROAD DAYLIGHT STUDIES

Abstract Background and aims Stroke risk stratification in Atrial Fibrillation (AF) and Embolic Stroke of Undetermined Source (ESUS) relies on prognostic markers rather than on the immediate thrombus substrate. We aimed to test a new concept in stroke risk stratification: Suboptimal Left Atrial Appendage Opacification, or SLAAO (/ˈsleɪ.oʊ/). SLAAO is a newly defined imaging mechanistic biomarker reflecting LAA hypocontractility and stasis. We aimed to assess 3 prespecified hypotheses: (1) SLAAO is associated with breakthrough strokes; (2) SLAAO explains risk gradients across AF phenotypes (AF detected after stroke, ECG-detected AF, and AF known before stroke); and (3) SLAOO may explain why previous ESUS anticoagulation trials failed, while asundexian (OCEANIC-STROKE) demonstrated benefit. Methods We analyzed ~550 participants from the prospective Phase III DAYLIGHT and Phase IV implementation BROAD-DAYLIGHT cohorts, including individuals with/without stroke, with/without AF. Sample size calculations estimated that 119 SLAAO events were needed to test the 3 prespecified hypotheses (see background). We used case-control and cross-sectional designs. SLAAO was newly defined as distal hypo-opacification or two novel variants related to contrast retention (focal/global), adjudicated on any contrast-enhanced thoracic CT. Directed Acyclic Graphs (DAGs) were used to identify confounding variables for multivariable analyses. Results Preliminary event-driven analysis of 135 SLAAO events in ~550 participants shows a strong signal supporting all three hypotheses. Final results will be presented at ESOC 2026. Conclusions SLAAO is a novel pathophysiological biomarker of stroke risk, easily identifiable by neurologists on standard CT with contrast including the heart, with multiple clinical implications, and the potential to change clinical practice. Conflict of interest