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 it remains unclear how fibrosis-related contractile impairment alters blood transport in the left atrium (LA) and left atrial appendage (LAA). Prior multi-physics simulations coupling electromechanical (EM) and computational fluid dynamics (CFD) models showed 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 applied globally to a common LA anatomy 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 local burdens of 10%, 25%, and 50%, yielding six LAA-fibrosis cases. A 3D EM model of the LA anatomy coupled to a 0D circulatory model resolved the reservoir, conduit, and booster phases, and the 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 (T _R ) were evaluated in the LA and LAA. Results: Left ventricular stroke volume remained nearly constant across cases, whereas increasing global fibrosis burden progressively reduced LA and LAA EF (LA: 36% to 30-31%; LAA: 44% to 28-38%), lowered both active and passive LA EF, and monotonically increased LA T _R 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 90th percentile of LAA T _R did not increase monotonically with decreasing LAA EF for one pattern. When fibrosis was confined to the LAA, non-dimensional LAA KE collapsed onto a single relationship with LAA EF for both patterns, whereas LAA T _R followed distinct, non-monotonic trends. Conclusions : Fibrosis burden, through its association with functional impairment, predominantly governed whole-LA hemodynamics, whereas LAA stasis additionally depended on the spatial distribution of fibrosis. In the LAA-fibrosis cases, LAA EF was a robust descriptor of chamber-averaged KE regardless of fibrosis pattern, but did not fully explain LAA residence time. These findings support evaluating imaging-derived fibrosis pattern, in addition to fibrosis burden and functional metrics, as a potential determinant of LAA transport and stasis. Its incremental value for thrombogenic-risk assessment requires prospective clinical validation.