Effects of atrial fibrosis induced by mitral regurgitation on atrial electrophysiology and susceptibility to atrial fibrillation in pigs

Background: The mechanism by which atrial fibrosis leads to the production and maintenance of atrial fibrillation (AF) is unclear. Myocardial biopsies, which have often been used in previous studies, are taken from a single site and do not always reflect the overall condition of atrial fibrosis. Aims: The aim of this study was to investigate the location of fibrosis in the atria induced by mitral regurgitation (MR) and its effect on atrial electrophysiology and vulnerability to AF. Methods: Nineteen pigs were divided into three groups. The control group (n=6) underwent a sham operation, and the experimental groups underwent an MR induction operation and were observed for 3 (n=7) or 6 (n=6) months. All the animals were tested for vulnerability to AF. Then, the atria were divided into 12 regions: 6 in the left atrium (LA) and 6 in the right atrium (RA). The conduction velocities (CVs) and effective refractory periods (ERPs) in different regions were examined by electroanatomic mapping, and fibrosis in different regions was examined by Masson staining. Results: With the duration of MR, fibrosis (3.11% +/- 0.08% in the control group, 5.85% +/- 0.42% in the 3-month group and 28.17% +/- 0.23% in the 6-month group, P<.001), vulnerability to AF (0/6 in the control group, 2/7 in the 3-month group and 5/6 in the 6-month group, P<.05) and the effective refractory period (220.1 +/- 1.1 ms in the control group, 244.4 +/- 1.4 ms in the 3-month group and 289.0 +/- 8.9 ms in the 6-month group, P<.001) were increased, while the conduction velocity (1.39 +/- 0.16 m/s in the control group, 1.04 +/- 0.05 m/s in the 3-month group and 0.89 +/- 0.02 m/s in the 6-month group, P<.001) was reduced. These pathophysiological changes were not uniform in different regions of the atria (3.83% +/- 0.25% in right atrial fibrosis vs 8.22% +/- 0.83% in left atrial fibrosis, P<.001; 5.09% +/- 0.34% in the right atrium vs 11.76% +/- 0.52% in the left atrium, P<.001). A negative correlation was identified between fibrosis and conduction velocity (P<.001 in the 3-month and 6-month groups), but no correlation was found between fibrosis and the effective refractory period (P=.829 in the 3-month group and P=.093 in the 6-month group). Susceptibility to AF was associated with the dispersion of atrial fibrosis (P=.023). Conclusions: With the duration of MR, atrial fibrosis increased, and the degree of increase was not uniform among different areas of the atria. The dispersion of atrial fibrosis may contribute to increased susceptibility to AF by influencing the conduction velocity rather than the effective refractory period. (C) 2019 Elsevier Inc. All rights reserved.