Mitral Valve Disease

Atrial fibrillation (AF) is highly prevalent and patients with AF have an increased thromboembolic risk compared to healthy individuals, with increased incidence of stroke and systemic thromboembolism. Oral anticoagulants are used to prevent the occurrence of clinical thromboembolic events in AF patients with a high thrombotic risk (calculated by the CHA₂DS₂-VA score). The use of oral anticoagulants, however, is accompanied by an increase in bleeding risk, especially in elderly patients and patients with comorbidities.

In a recent study we showed that moderate to severe mitral valve regurgitation (MR) reduces the thromboembolic risk in AF patients. In the present project we want to explore the causal relationship between MR and thrombotic risk in AF. To this end, we aim to develop an experimental porcine model to examine the pathophysiological effect of MR on this thrombotic risk. We will also further extrapolate our experience in a clinical study to research the possible protective effect of MR on the thrombotic risk.

In our experimental model, we will induce severe MR in pigs by cutting the chordae tendineae of the anterior mitral valve leaflet with a custom-made retractor, which will be introduced through the left ventricular apex under direct cardiac ultrasound imaging. A pilot study showed that this technique has minimal complications, a high success rate, and a high uniformity of the degree/regurgitant jet of MR. We will randomize pigs into two groups, a group with induction of severe MR and a sham group. We will evaluate the difference in thrombotic risk by performing blood sampling in the left atrium both in the acute and chronic phase (four weeks postoperatively). Furthermore, we will perform intraoperative epicardial ultrasound during the procedure and after four weeks of follow-up. At the end of the experiment, we will also perform an autopsy to preserve cardiac tissue for pathological analysis.

In our clinical study, we will determine blood biomarkers of thrombogenicity in patients with severe MR who undergo surgical repair with mitral valve annuloplasty or patients who receive percutaneous edge-to-edge mitral valve repair with the MitraClip™ device. We will evaluate the difference in thrombotic risk by performing blood sampling before the procedure, during the procedure (right before and after mitral valve repair), and after six months of follow-up. Furthermore, we will perform cardiac ultrasound imaging before and during the procedure, as well as after six months of follow-up to evaluate the MR and any structural changes in the heart. During follow-up we will also monitor for clinical thrombotic and bleeding events.

Finally, we will correlate the degree of MR with long-term thrombotic and bleeding risk in a large, unselected AF population by reviewing the AF-EduCare database.

If we can confirm the hypothesis that MR decreases thromboembolic risk, our findings will have important clinical implications, because a decreased thromboembolic risk could pave the way for clinical studies evaluating the downsizing of anticoagulant treatment in AF patients who are at high bleeding risk.

Funding: BOF

Researcher: Dr. Sven Van Laer

Promotor: Prof. Dr. Marc Claes

Co-promotor: Prof. Dr. Vincent Segers