Chiu Wei-Che, Girdhar Gaurav, Xenos Michalis, Alemu Yared, Soares Jõao S, Einav Shmuel, Slepian Marvin, Bluestein Danny
J Biomech Eng. 2014 Feb;136(2):021014. doi: 10.1115/1.4026254.
Approximately 7.5 × 106 patients in the US currently suffer from end-stage heart failure. The FDA has recently approved the designations of the Thoratec HeartMate II ventricular assist device (VAD) for both bridge-to-transplant and destination therapy (DT) due to its mechanical durability and improved hemodynamics. However, incidence of pump thrombosis and thromboembolic events remains high, and the life-long complex pharmacological regimens are mandatory in its VAD recipients. We have previously successfully applied our device thrombogenicity emulation (DTE) methodology for optimizing device thromboresistance to the Micromed Debakey VAD, and demonstrated that optimizing device features implicated in exposing blood to elevated shear stresses and exposure times significantly reduces shear-induced platelet activation and significantly improves the device thromboresistance. In the present study, we compared the thrombogenicity of the FDA-approved HeartMate II VAD with the DTE-optimized Debakey VAD (now labeled HeartAssist 5). With quantitative probability density functions of the stress accumulation along large number of platelet trajectories within each device which were extracted from numerical flow simulations in each device, and through measurements of platelet activation rates in recirculation flow loops, we specifically show that: (a) Platelets flowing through the HeartAssist 5 are exposed to significantly lower stress accumulation that lead to platelet activation than the HeartMate II, especially at the impeller-shroud gap regions (b) Thrombus formation patterns observed in the HeartMate II are absent in the HeartAssist 5 (c) Platelet activation rates (PAR) measured in vitro with the VADs mounted in recirculation flow-loops show a 2.5-fold significantly higher PAR value for the HeartMate II. This head to head thrombogenic performance comparative study of the two VADs, one optimized with the DTE methodology and one FDA-approved, demonstrates the efficacy of the DTE methodology for drastically reducing the device thrombogenic potential, validating the need for a robust in silico/in vitro optimization methodology for improving cardiovascular devices thromboresistance.
目前，美国约有750万名患者患有终末期心力衰竭。由于其机械耐用性和改善的血流动力学，美国食品药品监督管理局（FDA）最近批准了Thoratec HeartMate II心室辅助装置（VAD）用于桥接移植和目标治疗（DT）。然而，泵血栓形成和血栓栓塞事件的发生率仍然很高，并且其VAD接受者必须终生采用复杂的药物治疗方案。我们之前已成功将我们的装置血栓形成模拟（DTE）方法应用于优化Micromed Debakey VAD的装置抗血栓性，并证明优化与使血液暴露于升高的剪切应力和暴露时间相关的装置特征可显著降低剪切诱导的血小板活化，并显著改善装置抗血栓性。在本研究中，我们比较了FDA批准的HeartMate II VAD与经DTE优化的Debakey VAD（现标记为HeartAssist 5）的血栓形成性。通过从每个装置中的数值流模拟中提取的沿每个装置内大量血小板轨迹的应力累积的定量概率密度函数，并通过测量再循环流回路中的血小板活化率，我们具体表明：（a）流经HeartAssist 5的血小板暴露于导致血小板活化的应力累积明显低于HeartMate II，尤其是在叶轮-护罩间隙区域；（b）在HeartMate II中观察到的血栓形成模式在HeartAssist 5中不存在；（c）在再循环流回路中安装VAD体外测量的血小板活化率（PAR）显示，HeartMate II的PAR值显著高出2.5倍。这两种VAD的头对头血栓形成性能比较研究中，一种采用DTE方法进行了优化，另一种是FDA批准的，证明了DTE方法在大幅降低装置血栓形成潜力方面的有效性，验证了需要一种强大的计算机模拟/体外优化方法来改善心血管装置的抗血栓性。
