Uncovering the etiological mechanisms of mechanical cardiac device-induced thrombosis

Abstract

While life-saving, continuous-flow left ventricular assist devices (CF-LVADs) are associated with significant risks of thrombosis, necessitating lifelong antithrombotic therapy. Pump thrombosis and thromboembolic complications remain persistent challenges despite advancements in device technology. Data presented in this dissertation indicate that patients with CF-LVADs are in a hypercoagulable state while receiving antithrombotic therapy. This state is driven by persistent endothelial-, platelet- and contact system activation, likely due to the artificial surface of the device and the high shear stress it generates. These findings advance our understanding of the mechanisms behind mechanical cardiac device-induced thrombosis and provide a foundation for developing more effective preventive strategies. Moreover, our findings indicate that continuous exposure to shear stress of the CF-LVAD leads to platelet dysfunction, depleting platelet storage pools and increasing the risk of hemorrhage. This highlights the difficulty of balancing effective antithrombotic therapy with the prevention of bleeding. To be able to investigate the thrombogenicity of cardiac devices or evaluate the effectiveness and safety of new antithrombotic therapies with respect to artificial surface, shear stress and flow field, we developed the in-vitro model MarioHeart. The model features a closed torus containing a mechanical heart valve, resembling the anatomical geometry of the proximal ascending aorta and aortic annulus. MarioHeart has a simple design which induces well-defined fluid dynamics resulting in physiologically non-turbulent flow without stasis of the blood by generating flow through the valve by semirotational motion of the fluid-filled torus. This model presents an innovative approach to in-vitro flow testing by avoiding internal driving systems and superfluous moving components.