Continuous Flow Ventricular Assist Device-Induced Platelet Dysfunction

描述（由申请人提供）：充血性心力衰竭（CHF）在西方世界是一种日益严重的流行病，在美国有550万人患有此病，每年新增55万患者。即使有了改进的医疗设备、急性冠状动脉介入治疗和手术技术，CHF的1年和5年死亡率分别为10%和80%，在过去20年里几乎没有变化。唯一确定的治疗方法是心脏移植，但仍然受到数量（每年可获得2200颗供体心脏）和费用的限制。心室辅助装置（VADs）通过泵血与衰竭的心室并行工作，为终末期心力衰竭提供了另一种治疗方法。上一代vad存在并发症和耐用性问题。新一代的连续血流VADs （CFVADs）利用单个转子输送血液，克服了旧VADs的局限性，显著减少了并发症，并实现了接近心脏移植的一年生存率；然而，重大挑战依然存在。高达30%的CFVAD受者经历与获得性血管性血友病因子（VWF）缺乏相关的非手术性出血，这被认为是由血液在穿过CFVAD时经历的高剪切率引起的。与VWF改变同时发生的还有单独的血小板粘附缺陷。在初步研究中，我们观察到VWF在接受临床试验的新型CFVAD的VAD受者和一名不同类型CFVAD的患者中得以保存，该患者在VAD植入后由于心脏自发恢复而在脱机期间泵速大幅降低。因此，获得性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。考虑到开发治疗CHF的巨大需求和减少CFVAD显著并发症的潜力，我们提出：1)使用一种新的微通道方法来研究CFVAD受者的VWF和血小板功能改变；2)使用改良的微通道和模拟循环回路与整体CFVAD，研究和量化产生观察到的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.