The effect of short-term mitral valve regurgitation on atrial remodelling and atrial fibrillation inducibility in an experimental porcine model

Abstract Background/Introduction Mitral valve regurgitation (MR) is known to be interrelated with atrial fibrillation (AF): MR and AF both cause remodelling and dilation of the left atrium, which in turn causes MR and AF. However, the effects of short-term MR on atrial remodelling and AF inducibility are not well studied. Purpose The present experimental study aims to assess the effect of short-term MR on atrial remodelling and AF inducibility in pigs. Methods A total of 21 Piétrain pigs (with equal gender distribution) of sixteen weeks old with an average weight of 40 kg were included in the study. The pigs were randomized to the MR group (n = 14) or the sham group (n = 7). We developed a technique to induce severe MR after sternotomy, by cutting the chordae tendineae of one of the mitral valve leaflets with a custom-made retractor inserted through the left ventricular apex under direct epicardial ultrasound imaging. The sham procedure was identical, including the insertion of the retractor through the left ventricular apex, but without cutting the chordae tendineae. Epicardial ultrasound images were made intraoperatively to assess left atrial dimensions and MR severity by using the multi-integrative criteria as described in the ESC guidelines. The follow-up time was 4 weeks, during which the pigs received diuretic treatment and daily clinical observation. After 4 weeks, atrial tachypacing (consisting of 10 burst pacings of 50 Hz, each during 5, 10, and 15 seconds with intervals of 10 seconds after AF termination) was performed using a decapolar catheter introduced into the right atrium through a femoral sheath. AF inducibility (defined as percentage of bursts which induced AF lasting 10 seconds) and cumulative AF duration were assessed. At the end of the follow-up procedure, biopsies were taken from the left atrial appendage and the left atrial free wall for Masson’s trichrome staining to quantify left atrial fibrosis. Results Echocardiographic evaluation at 4 weeks showed MR severity grade 3+ to 4/4 in all pigs of the intervention group. AF inducibility was 41.2 ± 22.9 % in the pigs with severe MR and 9.5 ± 10.6 % in the sham group (p = 0.004, Figure 1). Cumulative duration of AF after burst pacing was significantly higher in the MR group (535 (406.5 – 2071.8) seconds vs. 95 (33.5 – 343.5) seconds, p = 0.016). There was evidence of left atrial dilation at 4 weeks in the MR group, which showed significantly larger left atrial volumes (54.9 ± 18.9 cm³ vs. 37.3 ± 6.5 cm³, p = 0.043). The pigs with severe MR showed a significantly higher amount of left atrial fibrosis, both in the left atrial appendage (25.8 ± 5.2 % vs. 13.0 ± 2.9 %, p 0.001, Figure 2) and in the left atrial free wall biopsies (23.8 ± 5.7 % vs. 17.7 ± 3.1 %, p = 0.016). Conclusion Our data suggest that short-term MR of only 4 weeks causes significant and clinically important atrial remodelling, with significantly increased vulnerability to develop AF.Figure 1.AF inducibility (p = 0.004) Figure 2.LA fibrosis (p 0.001)