Fibrosis burden and spatial pattern affect left atrial appendage stasis in multi-beat multi-physics simulations

Abstract

Purpose: Atrial fibrosis is associated with thromboembolic risk in atrial fibrillation, but how fibrosis-related contractile impairment alters blood transport in the left atrium (LA) and left atrial appendage (LAA) remains unclear. Prior multi-physics simulations coupled electromechanical (EM) and computational fluid dynamics (CFD) models to show that fibrosis impairs LA function and flow, but were limited to booster-only contraction and could not separate the effects of fibrosis burden from its spatial distribution. Here we examined how fibrosis burden and spatial pattern independently relate to long-term LA and LAA hemodynamics in full-cycle, multi-beat simulations on a common LA anatomy. Methods: Three fibrosis patterns derived from late gadolinium enhancement MRI were considered: one from the patient providing the common anatomy and two from additional patients, with the latter mapped onto the common anatomy via universal atrial coordinates. All three patterns were applied globally at matched burdens of 15.6% and 31.2%, yielding six global-fibrosis cases and a non-fibrotic reference. Two patterns were also confined to the LAA at three local burdens (10%, 25%, and 50%), yielding six LAA-fibrosis cases. A 3D EM model for the LA anatomy was coupled to a 0D circulatory model, so that the simulations resolved the reservoir, conduit, and booster phases. Full-cycle EM-derived wall motion drove subsequent multi-beat CFD simulations. Region-specific emptying fraction (EF), non-dimensional kinetic energy (KE), and the 90th percentile of blood residence time (TR) were evaluated for the LA and LAA. Results: Left ventricular stroke volume remained nearly constant across cases, while increasing global fibrosis burden progressively reduced LA and LAA EF (LA: 36% to 30-31%; LAA: 44% to 28-38%) and monotonically increased LA TR across all patterns. Non-dimensional LA KE showed an approximately quadratic association with LA EF across patterns, whereas LAA KE was more scattered but still increased with LAA EF. In contrast, the relationship between the 90th percentile of LAA TR and LAA EF showed pattern-specific, non-monotonic trends. Conclusions: Fibrosis burden and spatial distribution jointly shape LA and LAA hemodynamics, but through different mechanisms. LAA EF is a robust functional descriptor of chamber-averaged kinetic energy regardless of fibrosis pattern, whereas LAA blood stasis depends additionally on the spatial distribution of fibrosis beyond what bulk emptying fraction predicts. These findings support incorporating imaging-derived fibrosis pattern, and not only burden, alongside functional metrics when assessing thrombogenic risk in the LAA.