Device Thrombogenicity Emulation: A Novel Method for Optimizing Mechanical Circulatory Support Device Thromboresistance

摘要: Mechanical circulatory support (MCS) devices provide both short and long term hemodynamic for advanced heart failure patients. Unfortunately these remain plagued by thromboembolic complications associated with chronic platelet activation – mandating complex, lifelong anticoagulation therapy. To address the unmet need enhancing thromboresistance of to extend their use, we developed a universal predictive methodology entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing thrombogenic performance any MCS device ideally level may obviate mandatory anticoagulation. DTE combines in silico numerical simulations vitro measurements correlating hemodynamics activity coagulation markers before after iterative design modifications aimed at achieving optimized performance. DTE proof-of-concept is demonstrated comparing two rotary Left Ventricular Assist Devices (LVADs) (DeBakey vs HeartAssist 5, Micromed Houston, TX), latter version former following optimization geometrical features implicated thrombogenicity. Cumulative stresses drive platelets beyond threshold were calculated along multiple flow trajectories collapsed into probability density functions (PDFs) representing ‘thrombogenic footprint’, indicating significantly reduced thrombogenicity design. Platelet performed actual pump prototypes operating under clinical conditions circulation loops methodology, show an order magnitude lower rate device. The robust capability this technology here attaining safe cost-effective pre-clinical thrombo-optimization indicates its potential reducing limit extent concomitant antithrombotic pharmacotherapy needed use.