Data_Sheet_1_Wavelength and Fibrosis Affect Phase Singularity Locations During Atrial Fibrillation.PDF

The mechanisms underlying atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, remain elusive. Atrial fibrosis plays an important role in the development of AF and rotor dynamics. Both electrical wavelength (WL) and the degree of atrial fibrosis change as AF progresses. However, their combined effect on rotor core location remains unknown. The aim of this study was to analyze the effects of WL change on rotor core location in both fibrotic and non-fibrotic atria. Three patient specific fibrosis distributions (total fibrosis content: 16.6, 22.8, and 19.2%) obtained from clinical imaging data of persistent AF patients were incorporated in a bilayer atrial computational model. Fibrotic effects were modeled as myocyte-fibroblast coupling + conductivity remodeling; structural remodeling; ionic current changes + conductivity remodeling; and combinations of these methods. To change WL, action potential duration (APD) was varied from 120 to 240ms, representing the range of clinically observed AF cycle length, by modifying the inward rectifier potassium current (IK1) conductance between 80 and 140% of the original value. Phase singularities (PSs) were computed to identify rotor core locations. Our results show that IK1 conductance variation resulted in a decrease of APD and WL across the atria. For large WL in the absence of fibrosis, PSs anchored to regions with high APD gradient at the center of the left atrium (LA) anterior wall and near the junctions of the inferior pulmonary veins (PVs) with the LA. Decreasing the WL induced more PSs, whose distribution became less clustered. With fibrosis, PS locations depended on the fibrosis distribution and the fibrosis implementation method. The proportion of PSs in fibrotic areas and along the borders varied with both WL and fibrosis modeling method: for patient one, this was 4.2–14.9% as IK1 varied for the structural remodeling representation, but 12.3–88.4% using the combination of structural remodeling with myocyte-fibroblast coupling. The degree and distribution of fibrosis and the choice of implementation technique had a larger effect on PS locations than the WL variation. Thus, distinguishing the fibrotic mechanisms present in a patient is important for interpreting clinical fibrosis maps to create personalized models.

房颤（AF）这一最常见的持续心脏节律紊乱的潜在机制尚难以捉摸。心房纤维化在AF的发展中扮演着至关重要的角色，而旋转动力学亦然。随着AF的进展，电波长（WL）以及心房纤维化的程度均会发生改变。然而，它们对旋转核心位置的联合影响仍属未知。本研究旨在分析WL变化对纤维化和非纤维化心房中旋转核心位置的影响。本研究从持续AF患者的临床成像数据中获得了三个患者特异性的纤维化分布（总纤维化含量分别为16.6%，22.8%，和19.2%），并将其纳入双层心房计算模型中。纤维化效应被建模为肌细胞-成纤维细胞耦合+传导性重塑；结构重塑；离子电流变化+传导性重塑；以及这些方法的组合。为了改变WL，通过调节内向整流钾电流（IK1）的传导性，将动作电位持续时间（APD）从120ms变化至240ms，以代表临床观察到的AF周期长度的范围。通过计算相奇点（PSs）来识别旋转核心位置。我们的结果显示，IK1传导性的变化导致了心房内APD和WL的降低。在无纤维化的情况下，PSs定位于左心房（LA）前壁中心以及肺静脉（PVs）与LA交界处，这些区域具有高APD梯度。减小WL诱导出更多的PSs，其分布变得更加分散。在有纤维化的情况下，PS的位置取决于纤维化分布和纤维化实现方法。纤维化区域和边界上的PS比例随WL和纤维化建模方法的变化而变化：对于患者一，当IK1变化时，结构重塑表示的比例为4.2%-14.9%，而结合结构重塑与肌细胞-成纤维细胞耦合时，比例为12.3%-88.4%。纤维化的程度和分布以及实现技术的选择对PS位置的影响大于WL的变化。因此，区分患者中存在的纤维化机制对于解读临床纤维化图谱以创建个性化模型至关重要。