Degree of Fibrosis in Human Atrial Tissue Is Not the Hallmark Driving AF

Kennedy S. Ramos, Lisa Pool, Mathijs S. van Schie, Leonoor F. J. M. Wijdeveld, Willemijn F. B. van der Does, Luciënne Baks, H. M. Danish Sultan, Stan W. van Wijk, Ad J. J. C. Bogers, Sander Verheule, Natasja M. S. de Groot, Bianca J. J. M. Brundel

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Background: The current paradigm is that fibrosis promotes electrophysiological disorders and drives atrial fibrillation (AF). In this current study, we investigated the relation between the degree of fibrosis in human atrial tissue samples of controls and patients in various stages of AF and the degree of electrophysiological abnormalities. Methods: The degree of fibrosis was measured in the atrial tissue and serum of patients in various stages of AF and the controls. Hereto, picrosirius and H&E staining were performed to quantify degree of total, endo-perimysial fibrosis, and cardi-omyocyte diameter. Western blot quantified fibrosis markers: neural cell adhesion molecule, tissue inhibitor of metalloproteinase, lysyl oxidase, and α-smooth muscle actin. In serum, the ratio car-boxyl-terminal telopeptide of collagen/matrix-metalloproteinase1 was determined. High-resolution epicardial mapping evaluated low-voltage areas and conduction abnormalities. Results: No significant differences were observed in the degree of fibrosis between the groups. Finally, no significant correlation—absolute nor spatial—was observed between all electrophysiological parameters and histological fibrosis markers. Conclusions: No differences in the degree of fibrosis were observed in patients from various stages of AF compared to the controls. Moreover, electrophysiological abnormalities did not correlate with any of the fibrosis markers. The findings indicate that fibrosis is not the hallmark of structural remodeling in AF.
Original languageEnglish
Article number427
Issue number3
Publication statusPublished - 26 Jan 2022


  • (bio)markers
  • Atrial fibrillation
  • Cardiac mapping
  • Electrical remodeling
  • Fibrosis
  • Structural remodeling

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