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.

It is unknown to what extent atrial fibrillation (AF) episodes affect intra-atrial conduction velocity (CV) and whether regional differences in local CV heterogeneities exist during sinus rhythm. This case-control study aims to compare CV assessed throughout both atria between patients with and without AF. Patients (n = 34) underwent intra-operative epicardial mapping of the right atrium (RA), Bachmann’s bundle (BB), left atrium (LA) and pulmonary vein area (PVA). CV vectors were constructed to calculate median CV in addition to total activation times (TAT) and unipolar voltages. Biatrial median CV did not differ between patients with and without AF (90 ± 8 cm/s vs. 92 ± 6 cm/s, p = 0.56); only BB showed a CV reduction in the AF group (79 ± 12 cm/s vs. 88 ± 11 cm/s, p = 0.02). In patients without AF, there was no predilection site for the lowest CV (P₅) (RA: 12%; BB: 29%; LA: 29%; PVA: 29%). In patients with AF, lowest CV was most often measured at BB (53%) and ranged between 15 to 22 cm/s (median: 20 cm/s). Lowest CVs were also measured at the LA (18%) and PVA (29%), but not at the RA. AF was associated with a prolonged TAT (p = 0.03) and decreased voltages (P₅) at BB (p = 0.02). BB was a predilection site for slowing of conduction in patients with AF. Prolonged TAT and decreased voltages were also found at this site. The next step will be to determine the relevance of a reduced CV at BB in relation to AF development and maintenance.

We investigated whether patterns of activation at Bachmann’s bundle are related to AF inducibility. Epicardial mapping of Bachmann’s bundle during sinus rhythm was performed prior to cardiac surgery (192 electrodes, interelectrode distances: 2 mm). Compared to non-inducible patients (N = 20), patients with inducible AF (N = 34) had longer lines of conduction block (18(2–164) mm vs. 6(2–28) mm, p = 0.048), prolonged total activation time (55(28–143) ms vs. 46(24–73) ms, p = 0.012), multiple wavefronts entering Bachmann’s bundle more frequently (64% vs. 37%, p = 0.046) and more often areas of simultaneous activation (conduction velocity > 1.7 m/s, 45% vs. 16%, p = 0.038). These observations further support a relation between conduction abnormalities at Bachmann’s bundle and AF inducibility. The next step is to examine whether Bachmann’s bundle activation patterns can also be used to identify patients who will develop AF after cardiac surgery during both short- and long-term follow-up.

Classification of atrial fibrillation (AF) is currently based on clinical characteristics. However, classifying AF using an objective electrophysiological parameter would be more desirable. The aim of this study was to quantify parameters of atrial conduction during sinus rhythm (SR) using an intra-operative high-resolution epicardial mapping approach and to relate these parameters to clinical classifications of AF. Patients were divided according to the standard clinical classification and spontaneous termination of AF episodes. The HATCH score, a score predictive of AF progression, was calculated, and surface ECGs were evaluated for signs of interatrial block. Conduction disorders mainly differed at Bachmann’s bundle (BB). Activation time (AT) at BB was longer in persistent AF patients (AT-BB: 75 (53–92) ms vs. 55 (40–76) ms, p = 0.017), patients without spontaneous termination of AF episodes (AT-BB: 53.5 (39.6–75.8) ms vs. 72.0 (49.6–80.8) ms, p = 0.009) and in patients with a P-wave duration ≥ 120 ms (64.3 (52.3–93.0) ms vs. 50.5 (39.6–56.6) ms, p = 0.014). HATCH scores also correlated positively to AT-BB (rho 0.326, p = 0.029). However, discriminatory values of electrophysiological parameters, as calculated using ROC-curves, were limited. These results may reflect shortcomings of clinical classifications and further research is needed to establish an objective substrate-based classification of AF.