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

Abstract

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 cardiomyocyte 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 carboxyl-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.

Heart failure, female sex and atrial fibrillation are the main drivers of human atrial cardiomyopathy: results from the CATCH ME consortium

“…In goats, after 6 months of rapid atrial pacing-induced AF, atrial endomysial fibrosis increases, whereas quantities of total ECM remain constant (9), a combination of findings resembling well the findings of the current study. Recently, a study of cardiac surgery patients reported no association between electrophysiological parameters and histological fibrosis markers (59). Electrophysiological measurements, however, were performed at low rates and a distinction between total and endomysial fibrosis was only made in a small percentage of patients.…”

“…Recently, a study of cardiac surgery patients reported no association between electrophysiological parameters and histological fibrosis markers (59). Electrophysiological measurements, however, were performed at low rates and a distinction between total and endomysial fibrosis was only made in a small percentage of patients.…”

Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure

“…Recently, Ramos and colleagues could similarly demonstrate that in patients with AF the absolute degree of fibrosis is not the key driver for AF. 19 Furthermore, they could show that the heterogeneous distribution of fibrosis within the right atrial appendage does not correlate with altered electrical conduction properties. 19 As interstitial fibrosis has been demonstrated to establish local conduction heterogeneities leading to AF, [2][3][4]14 we hypothesized that not only localized but also cross-regional fibrosis heterogeneity contributes to AF.…”

Advances in basic and translational research in atrial fibrillation

“…Atrial fibrosis is a common feature in AF patients, yet how and if atrial fibrosis is involved in AF generation is poorly understood [91]. Ramos et al reported recently that the amount of atrial fibrosis is not different in patients with various stages of AF and controls [92]. It is atrial structural remodelling rather than atrial fibrosis that can be causal for AF [92].…”

“…Ramos et al reported recently that the amount of atrial fibrosis is not different in patients with various stages of AF and controls [92]. It is atrial structural remodelling rather than atrial fibrosis that can be causal for AF [92]. Interestingly, mild and moderate atrial fibrosis has been reported to be associated with an increase of AF burden and advanced atrial fibrosis (encountered in patients with severe HF) is associated with a reduction of AF burden [93,94].…”