Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts
Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts
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DOI：
10.1093/eurheartj/ehv233
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发表时间：
2015-09-14
影响因子：
39.3
通讯作者：
Fedorov, Vadim V.
中科院分区：
文献类型：
--
作者：
Hansen, Brian J.;Zhao, Jichao;Fedorov, Vadim V.
目的人类心房的复杂结构可能为持续的再入创造物理基质，从而驱动心房颤动（AF）。由于缺乏同时进行的心内膜-心外膜（Endo-Epi）制图以及高分辨率的3D结构成像，在人类中存在持续的、解剖学上定义的房颤驱动因素一直受到挑战。方法和结果用3台高分辨率CMOS相机（2台对准Endo-Epi视图（330 μ m(2)分辨率）和1台全景视图）同时对8例43 ~ 72岁病变心脏的冠状动脉灌注的右心房进行光学定位。三维钆增强磁共振成像（GE-MRI, 80 μ m(3)分辨率）显示心房壁结构厚度变化（1.0 +/- 0.7-6.8 +/- 2.4 μ m），跨壁纤维角度差异，间质纤维化导致跨壁激活延迟，从23 +/- 11 ms到43 +/- 22 ms。持续AF （）pinacidil （30 ~ 100 μ M）灌注时，以爆发性起搏诱导小鼠生长90 min。双侧亚内径-亚外径光学图谱显示AF是由空间和时间稳定的腔内再入驱动的，周期长度为107 +/- 50 ms，跨壁激活延迟为67 +/- 31 ms。内部再入驱动程序主要通过子endo映射捕获，而子epi映射则可视化再入或“突破”模式。再入驱动器被锚定在心房肌组织形成的三维显微解剖轨道上（15.4 +/- 2.2 x 6.0 +/- 2.3 μ m(2), 2.9 +/- 0.9 μ m深度），其特征是跨壁纤维角度差异增加和间质纤维化。结论对患病的人的离体心房进行三维结构-功能综合成像显示，复杂的心房微结构导致起搏时Endo和Epi的激活，以及由固定在纤维化隔离心房束上的心房内再进入驱动的持续心房颤动之间存在显著差异。
Aims The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging.Methods and results Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 mu m(2) resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 mu m(3) resolution) revealed the atrial wall structure varied in thickness (1.0 +/- 0.7-6.8 +/- 2.4 mu m), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 +/- 11 to 43 +/- 22 ms at increased pacing rates. Sustained AF (. 90 min) was induced by burst pacing during pinacidil (30-100 mu M) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 +/- 50 ms cycle length and transmural activation delay of 67 +/- 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 +/- 2.2 x 6.0 +/- 2.3 mu m(2), 2.9 +/- 0.9 mu m depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF.Conclusions Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles.