The effect of high-flow and low-flow conditions on left atrial thrombotic risk: a porcine model of mitral valve regurgitation and lone atrial fibrillation

Background/Introduction Atrial fibrillation (AF) and its underlying atrial myopathy increase the left atrial thrombotic risk, as calculated by the CHA2DS2-VA score, which correlates well with the presence of atrial myopathy. However, the risk prediction of this score is modest (C-statistic = 0.60). Other factors, such as mitral valve regurgitation (MR), may influence thrombotic risk. In nonrheumatic AF, however, the effect of MR on left atrial thrombotic risk remains controversial. Furthermore, the thrombotic effect of AF itself, without underlying atrial myopathy, is not well studied. Purpose To assess the effect of MR (high flow) and lone AF (low flow) on left atrial thrombotic risk. Methods A total of 20 Piétrain pigs (with equal sex distribution) were randomized to severe MR, induced by selective cutting of the chordae tendineae (n = 14), or the sham procedure (n = 6). High-frequency atrial tachypacing was performed to induce paroxysmal AF (15 min.). Left atrial blood samples were collected before and after AF-induction. After four weeks, blood sampling was repeated in all pigs, and the sham group underwent a longer AF-tachypacing session (60 min.). To explore left atrial thrombotic risk, platelet aggregation, intrinsic, extrinsic, and common coagulation pathways, and fibrinolysis were measured. Results Echocardiographic evaluation after four weeks showed MR severity grade 3.5 to 4/4 in all pigs of the intervention group. Severe MR led to left atrial dilation, with a greater increase in mean left atrial volume compared to the sham group (+28.1 ± 5.4 ml vs. +6.7 ± 2.1 ml; p = 0.01), and more left atrial fibrosis (25.8 ± 5.2% vs. 13.0 ± 2.9%; p < 0.001). There was a significantly divergent effect of MR vs. AF on left atrial thrombotic risk (P-values for all interactions < 0.05, Figure 1). MR was associated with increases in mean platelet volume (MPV, +9.1%), APTT (+9.6%), PT (+8.5%), and D-dimers (+54.0%), and decreases in platelet aggregation (-9.7%) and fibrinogen (-23.1%), indicating an antithrombotic effect. The opposite effect was observed for AF, with decreases in MPV (-2.2%), APTT (-1.1%), and PT (-1.9%), and increases in platelet aggregation (+1.4%) and fibrinogen (+2.2%), indicating a prothrombotic effect. Conclusion Our data show a prothrombotic effect of lone AF (low flow) and an antithrombotic effect of MR (high flow) on left atrial thrombotic risk. The antithrombotic effect of MR was observed despite the development of atrial myopathy, as evidenced by atrial dilation and fibrosis. This implies that MR could be a modifying protective factor in thrombotic risk assessment of AF patients and could help individualize anticoagulant treatment. The data of our lone AF model, without underlying atrial myopathy, emphasizes the importance of adequate rhythm control in AF patients to minimize left atrial thrombogenicity and also challenges the safety of withholding anticoagulation in patients with a low CHA2DS2-VA score and persistent AF.