Continuous Flow Ventricular Assist Device-Induced Platelet Dysfunction

描述(申请人提供)：充血性心力衰竭(CHF)是一种在西方世界日益流行的疾病，在美国有550万人受到影响，每年新增55万名确诊患者。即使有了改进的医疗设备、急性冠状动脉介入治疗和外科技术，CHF的一年和五年死亡率仍为10%和80%，在过去20年中几乎没有变化。唯一确定的治疗方法是心脏移植，但这仍然受到数量(每年可获得2200例供者心脏)和成本的限制。心室辅助装置(VAD)通过泵血与衰竭的心脏并行工作，为终末期心力衰竭提供了一种替代治疗方法。上一代VAD饱受并发症和耐用性问题的困扰。利用单个转子输送血液的新一代连续流VAD(CFVADs)克服了老式VADs的局限性，显著减少了并发症，实现了接近心脏移植的一年存活率；然而，仍然存在重大挑战。多达30%的CFVAD受者经历与获得性血管性血友病因子(VWF)缺乏有关的非手术出血，被认为是血液在穿过CFVAD时经历的高切变率所致。一个单独的血小板粘连缺陷似乎也与VWF的改变同时发生。在初步研究中，我们观察了VAD受者和一名患有不同类型CFVAD的患者VWF的保存情况，这些患者接受了一种正在进行临床试验的新型CFVAD，由于VAD植入后的自发心脏恢复，该患者的泵速度在脱机期间显著降低。因此，后天获得的VWF缺陷似乎不是CFVAD固有的，可能会随着设计或操作的改变而改变。鉴于开发CHF治疗方法的巨大需求以及减少CFVAD显著并发症的可能性，我们建议1)使用一种新的微通道方法来研究CFVAD受者VWF和血小板功能的变化；2)使用改进的微通道和带有完整CFVAD的模拟循环环，调查和量化导致所观察到的VWF和血小板功能障碍的剪切条件。

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is a growing epidemic in the Western World, afflicting 5.5 million people in US, with an additional 550,000 new victims diagnosed each year. Even with improved medical devices, acute coronary interventions, and surgical techniques, the one and five year mortality rates for CHF are 10% and 80%, virtually unchanged in the past two decades. The only definitive therapy is heart transplantation, but that remains limited by number (2,200 donor heart available each year) and cost. Ventricular assist devices (VADs), which work in parallel with a failing ventricular by pumping blood, offer an alternative treatment for end-stage heart failure. Previous generation VADs were plagued with complications and durability concerns. A new generation of continuous flow VADs (CFVADs), which utilize a single rotor to impart blood flow are overcoming the limitations of older VADs, significantly reducing complications and achieving one year survival rates approaching that of heart transplants; however, significant challenges remain. Up to 30% of CFVAD recipients experience non-surgical bleeding related to an acquired von Willebrand Factor (VWF) deficiency, thought to be caused by the high shear rates blood experiences as it traverses through the CFVAD. A separate platelet adhesion defect also appears to occur in concert with the VWF alternations. In preliminary studies, we have observed preservation of VWF in VAD recipients with a new CFVAD undergoing clinical trials and in a single patient with a different type of CFVAD whose pump speed was substantially reduced during weaning due to spontaneous cardiac recovery post-VAD implant. Thus, the acquired VWF deficiency does not appear to be inherent to CFVADs and may be altered with changes in design or operation. Given the tremendous need to development treatments for CHF and the potential to reduce a significant complication of CFVAD, we propose to 1) Use a novel microchannel approach to investigate VWF and platelet functional alternations in CFVAD recipients and 2) Using modified microchannels and mock circulatory loops with integral CFVADs, investigate and quantify the shear conditions which produce the observed VWF and platelet dysfunction.