MECHANISCHE HARTKLEPTROMBOSE: ONTWIKKELING VAN EEN GROOT DIERENMODEL EN NIEUWE STRATEGIEËN TER PREVENTIE

In recent long-term follow-up studies of patients after heart valve replacement surgery, mechanical valves still provide excellent outcomes. Mechanical valves are durable and can function for decades without structural deterioration or wear. The most important drawback of mechanical heart valves however, is their tendency to provoke thrombosis at the surface of the valve, causing either valve dysfunction or thrombo-embolic events to peripheral organs. The constant need for aggressive anticoagulation using coumadin not only interferes with patients' quality of life, but also has potential dangerous side effects such as spontaneous bleedings. Alternatives need to be found either in new, non-thrombogenic valve designs/materials, or in new treatment regimens avoiding coumadin-based anticoagulation. Large animal models to study valve thrombosis are not well defined. In this thesis project, a large animal model for mechanical valve thrombosis will be developed by implanting currently existing heart valves in pulmonary position, both in sheep as in pigs. The natural occurrence and characteristics of valve thrombosis will be studied with multiple modalities (echocardiography, acoustic analysis, fluoroscopy and detailed macro- and microscopical analyses). There are two potential strategies to address the issue of valve thrombosis: 1. Alternative medication: within this model of valve thrombosis, we will study whether new anticoagulant drugs such as apixaban, are able to prevent mechanical valve thrombosis. Such a finding will have large impact towards the clinical field. 2. Alternative valve design: new trileaflet mechanical heart valves have been designed with flow characteristics that resemble the flow in our native aortic valves and thereby function completely different to the currently used valve models. These new valves may be able to eliminate the need for coumadin-based anticoagulation. Findings of this thesis project will resonate into the field of thrombotic events in biological heart valves and will be relevant for pre-clinical testing of other new heart valve prostheses.