An in vitro biohybrid model for assessing the function of occluder systems for the left atrial appendage
Atrial fibrillation is the most common cardiac arrhythmia. Its global prevalence is rising steadily and was estimated at around 59 million people in 2019. Atrial fibrillation is associated with a five-fold increased risk of stroke. The main cause is the formation of blood clots in the left atrial appendage (LAA), where it has been shown that around 90 per cent of cardiac blood clots originate. For patients with contraindications to anticoagulation, percutaneous left atrial appendage occlusion (LAAO) represents a valuable alternative for reducing the risk of cardioembolic stroke. This involves the catheter-based implantation of an occluder system to physically isolate the LAA from the systemic circulation. However, periprosthetic leaks and device-associated thrombi remain significant complications associated with adverse clinical events.
The functional evaluation of LAAO systems is currently being carried out in vivo in canine models. The following aspects are being investigated: (i) the shape and anatomical fit of the implant (constriction or impairment of adjacent structures), (ii) the sealing of the implant and the occurrence of periprosthetic leaks, (iii) haemocompatibility, and (iv) endothelialisation. In addition to ethical concerns, the canine model has several limitations. The animals used in preclinical studies are healthy and therefore have a lower risk of thrombus formation [8–10]. Furthermore, the atrial ears of dogs differ from those of humans, as their lobes are less sharply angled [11]. This may influence the positioning of the implant and lead to differences in terms of periprothetic leaks and the formation of device-associated thrombi. Consequently, the transferability of the results to humans is limited.
The aim of this project is to develop an in vitro biohybrid model for evaluating the performance of LAAO systems under pathological conditions of human atrial fibrillation (Figure 1). The model consists of an elastomeric anatomical replica of a human left atrium, coupled to a circulatory simulator. This is intended to reproduce the conditions of atrial fibrillation, in particular the pathological flow and pressure profiles as well as the fluttering motion of the atrial wall.
The model of the left atrium is fabricated on the basis of clinical CT data and can be seeded with human endothelial cells. This enables the investigation of biological aspects such as endothelial cell activation and the endothelialisation of the implant. Through the integration of an ultrasound probe, transoesophageal echocardiography (TEE) will be utilised to assess the adaptability and sealing function of LAAO systems, as well as the formation of thrombi under clinically relevant conditions. The proposed biohybrid model is intended to facilitate the development and testing of LAAO systems, as well as their comparison with clinical data. Furthermore, it can be used to optimise the implantation procedure in terms of implant size and position.
