The effect of mitral valve regurgitation and lone atrial fibrillation on left atrial thrombotic risk: a porcine model of alternating left atrial flow conditions
S Van Laer, B Goovaerts, S Laga, M Tubeeckx, K Vanhoorelbeke, S Deconinck, I Pareyn, H Heidbuchel, V Segers, M ClaeysAbstract
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=0.6). Other factors, such as mitral valve regurgitation (MR), may influence thrombotic risk. In nonrheumatic AF, the effect of MR on left atrial thrombotic risk remains controversial. Furthermore, the thrombotic effect of AF itself, without 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, fibrinolysis, and von Willebrand factor (vWF) assays were measured.
Results
Echocardiography showed MR severity grade 3.5-4/4 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%), fibrinogen (-23.1%), and vWF antigen (-18.1%) and activity (-31.1%), 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%), fibrinogen (+2.2%), and vWF antigen (+3.4%) and activity (+4.1%), indicating a prothrombotic effect.
Conclusion
Our data show a prothrombotic effect of lone AF and an antithrombotic effect of MR on left atrial thrombotic risk. The antithrombotic effect of MR was observed despite the development of significant atrial myopathy. 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 AF model, without underlying atrial myopathy, emphasizes the importance of rhythm control in AF patients to minimize left atrial thrombogenicity and challenges safety of withholding anticoagulation in patients with low CHA2DS2-VA scores and persistent AF.Effect of MR and AF on thrombotic risk