Comprehensive evaluation of electrophysiological and 3D structural features of human atrial myocardium with insights on atrial fibrillation maintenance mechanisms.
Comprehensive evaluation of electrophysiological and 3D structural features of human atrial myocardium with insights on atrial fibrillation maintenance mechanisms.
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人类心房肌电生理学和三维结构特征的综合评价与心房颤动维持机制的见解。
DOI：
10.1016/j.yjmcc.2020.10.012
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发表时间：
2021-03
影响因子：
5
通讯作者：
Fedorov VV
中科院分区：
文献类型：
--
作者：
Mikhailov AV;Kalyanasundaram A;Li N;Scott SS;Artiga EJ;Subr MM;Zhao J;Hansen BJ;Hummel JD;Fedorov VV
心房颤动 (AF) 的发生和维持与人类心房的电生理（复极和传导）和 3D 结构（纤维化、纤维方向和壁厚度）特征的逐渐重塑相关。 AF 病因的显着多样性导致人类心房 3D 结构内的致心律失常电生理和结构基质存在异质性。由于目前的临床方法尚未完全解决患者特异性的心律失常基质，因此基于机制的 AF 治疗仍然不发达。在这里，我们回顾了体内、离体和体外人类心脏研究的最新知识，并讨论这些研究如何为 AF 维持中心房电生理学和 3D 结构特征的协同作用提供新的见解。对手术获取的人类心房样本进行体外研究为研究广泛的 AF 病理学提供了绝佳的机会，包括单细胞动作电位、离子通道和基因/蛋白质表达的功能变化。然而，有限的样品尺寸阻碍了对异质 AF 基底和重入机制的评估。相比之下，冠状动脉灌注的离体人类心脏可以使用最先进的功能和结构技术进行研究，例如高分辨率近红外光学测绘和对比增强 MRI。这些成像方式可以解析房性心律失常的底物及其在维持房颤的折返机制中的作用，并验证临床方法。尽管如此，纵向研究在移植的人类心脏中并不可行。由于没有一种方法是完美的，我们建议将直接人类心房研究的优势与实验室和现实的患者特异性计算机模型中可用的高保真方法相结合，将阐明对 AF 机制的更深入了解。我们提出，从离体人类心脏研究到纵向临床相关房颤动物研究，最后到临床试验，有必要建立一个全面的转化管道，以确定患者特异性的心律失常基质并开发新的房颤治疗方法。
Atrial fibrillation (AF) occurrence and maintenance is associated with progressive remodeling of electrophysiological (repolarization and conduction) and 3D structural (fibrosis, fiber orientations, and wall thickness) features of the human atria. Significant diversity in AF etiology leads to heterogeneous arrhythmogenic electrophysiological and structural substrates within the 3D structure of the human atria. Since current clinical methods have yet to fully resolve the patient-specific arrhythmogenic substrates, mechanism-based AF treatments remain underdeveloped. Here, we review current knowledge from in-vivo, ex-vivo, and in-vitro human heart studies, and discuss how these studies may provide new insights on the synergy of atrial electrophysiological and 3D structural features in AF maintenance. In-vitro studies on surgically acquired human atrial samples provide a great opportunity to study a wide spectrum of AF pathology, including functional changes in single-cell action potentials, ion channels, and gene/protein expression. However, limited size of the samples prevents evaluation of heterogeneous AF substrates and reentrant mechanisms. In contrast, coronary-perfused ex-vivo human hearts can be studied with state-of-the-art functional and structural technologies, such as high-resolution near-infrared optical mapping and contrast-enhanced MRI. These imaging modalities can resolve atrial arrhythmogenic substrates and their role in reentrant mechanisms maintaining AF and validate clinical approaches. Nonetheless, longitudinal studies are not feasible in explanted human hearts. As no approach is perfect, we suggest that combining the strengths of direct human atrial studies with the high fidelity approaches available in the laboratory and in realistic patient-specific computer models would elucidate deeper knowledge of AF mechanisms. We propose that a comprehensive translational pipeline from ex-vivo human heart studies to longitudinal clinically relevant AF animal studies and finally to clinical trials is necessary to identify patient-specific arrhythmogenic substrates and develop novel AF treatments.
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影响因子：
5
作者：
Anne, Wirn;Willems, Rik;Heidbuchel, Hein
通讯作者：
Heidbuchel, Hein
影响因子：
168.9
作者：
Attia, Zachi, I;Noseworthy, Peter A.;Friedman, Paul A.
通讯作者：
Friedman, Paul A.
影响因子：
20.1
作者：
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通讯作者：
Poggesi, Corrado
影响因子：
37.8
作者：
ALBONI, P;MALCARNE, C;NARULA, OS
通讯作者：
NARULA, OS
影响因子：
37.8
作者：
Atienza, Felipe;Almendral, Jesus;Berenfeld, Omer
通讯作者：
Berenfeld, Omer