Quantitative assessment of transmural fibrosis profile in the human atrium: evidence for a three-dimensional arrhythmic substrate by slice-to-slice histology.

Autor:	Ravelli F; Laboratory of Biophysics and Translational Cardiology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, Italy.; CISMed-Centre for Medical Sciences, University of Trento, Trento, Italy., Masè M; Laboratory of Biophysics and Translational Cardiology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, Italy., Cristoforetti A; Laboratory of Biophysics and Translational Cardiology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, Italy., Avogaro L; Laboratory of Biophysics and Translational Cardiology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, Italy., D'Amato E; Department of Physics, University of Trento, Trento, Italy., Tessarolo F; Department of Industrial Engineering and BIOtech, University of Trento, Trento, Italy., Piccoli F; Department of Laboratory Medicine, Santa Chiara Hospital, Trento, Italy., Graffigna A; Department of Cardiac Surgery, Santa Chiara Hospital, Trento, Italy.
Jazyk:	angličtina
Zdroj:	Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology [Europace] 2023 Feb 16; Vol. 25 (2), pp. 739-747.
DOI:	10.1093/europace/euac187
Abstrakt:	Aims: Intramural fibrosis represents a crucial factor in the formation of a three-dimensional (3D) substrate for atrial fibrillation (AF). However, the transmural distribution of fibrosis and its relationship with atrial overload remain largely unknown. The aim of this study is to quantify the transmural profile of atrial fibrosis in patients with different degrees of atrial dilatation and arrhythmic profiles by a high-resolution 3D histology method. Methods and Results: Serial microtome-cut tissue slices, sampling the entire atrial wall thickness at 5 µm spatial resolution, were obtained from right atrial appendage specimens in 23 cardiac surgery patients. Atrial slices were picrosirius red stained, imaged by polarized light microscopy, and analysed by a custom-made segmentation algorithm. In all patients, the intramural fibrosis content displayed a progressive decrease alongside tissue depth, passing from 68.6 ± 11.6% in the subepicardium to 10-13% in the subendocardium. Distinct transmural fibrotic profiles were observed in patients with atrial dilatation with respect to control patients, where the first showed a slower decrease of fibrosis along tissue depth (exponential decay constant: 171.2 ± 54.5 vs. 80.9 ± 24.4 µm, P < 0.005). Similar slow fibrotic profiles were observed in patients with AF (142.8 ± 41.7 µm). Subepicardial and midwall levels of fibrosis correlated with the degree of atrial dilatation (ρ = 0.72, P < 0.001), while no correlation was found in subendocardial layers. Conclusions: Quantification of fibrosis transmural profile at high resolution is feasible by slice-to-slice histology. Deeper penetration of fibrosis in subepicardial and midwall layers in dilated atria may concur to the formation of a 3D arrhythmic substrate. Competing Interests: Conflict of interest: None declared. (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu