Objective: Interstitial fibrosis is a pathological expansion of the heart's inter-cellular collagen matrix. It is a potential complication of nonischemic cardiomyopathy (NICM), a class of diseases involving electrical and or mechanical dysfunction of cardiac tissue not caused by atherosclerosis. Patients with NICM and interstitial fibrosis often suffer from life threatening arrhythmias, which we aim to simulate in this study. Methods: Our methodology builds on an efficient discrete finite element (DFE) method which allows for the representation of fibrosis as infinitesimal splits in a mesh. We update the DFE method with a local connectivity analysis which creates a consistent topology in the fibrosis network. This is particularly important in nonischemic disease due to the potential presence of large and contiguous fibrotic regions and therefore potentially complex fibrosis networks. Results: In experiments with an image-based model, we demonstrate that our methodology is able to simulate reentrant electrical events associated with cardiac arrhythmias. These reentries depended crucially upon sufficient fibrosis density, which was marked by conduction slowing at high pacing rates. We also created a 2D test-case which demonstrated that fibrosis topologies can modulate transient conduction block, and thereby reentrant activations. Conclusion: Ventricular arrhythmias due to interstitial fibrosis in NICM can be efficiently simulated using our methods in medical image based geometries. Furthermore, fibrosis topology modulates transient conduction block, and should be accounted for in electrophysiological simulations with interstitial fibrosis. Significance: Our study provides methodology which has the potential to predict arrhythmias and to optimize treatments non-invasively for nonischemic cardiomyopathies.

中文翻译：

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间质纤维化网络的 3D 电生理学模型及其在非缺血性心肌病室性心律失常中的作用


目的：间质纤维化是心脏细胞间胶原基质的病理性扩张。它是非缺血性心肌病 (NICM) 的潜在并发症，非缺血性心肌病是一类涉及非动脉粥样硬化引起的心脏组织电和/或机械功能障碍的疾病。患有 NICM 和间质纤维化的患者经常患有危及生命的心律失常，我们的目的是在本研究中模拟这种情况。方法：我们的方法建立在高效的离散有限元 (DFE) 方法的基础上，该方法允许将纤维化表示为网格中的无穷小分裂。我们通过局部连接分析更新了 DFE 方法，该分析在纤维化网络中创建一致的拓扑。这在非缺血性疾病中尤其重要，因为可能存在大且连续的纤维化区域，因此可能存在复杂的纤维化网络。结果：在基于图像的模型的实验中，我们证明我们的方法能够模拟与心律失常相关的折返电事件。这些折返主要取决于足够的纤维化密度，其特点是高起搏速率下传导减慢。我们还创建了一个 2D 测试用例，证明纤维化拓扑可以调节瞬态传导阻滞，从而调节可重入激活。结论：使用我们基于医学图像的几何学方法，可以有效地模拟 NICM 中间质纤维化引起的室性心律失常。此外，纤维化拓扑调节瞬时传导阻滞，应在间质纤维化的电生理模拟中予以考虑。 意义：我们的研究提供了有可能预测心律失常并优化非缺血性心肌病的非侵入性治疗的方法。