Biology of Long-Term Mechanical Circulatory Support

描述（由申请人提供）： 充血性心力衰竭（CHF）是一种非常普遍的病态。随机试验 已经表明，在患有难治性终末期疾病的心力衰竭患者亚组中，一年死亡率范围为50%至75%。结果比乳腺癌、结肠癌甚至肺癌更糟。药物治疗为这些患者提供的益处有限，而心脏移植则受到人类供体短缺的严重限制。植入式左心室辅助装置（LVAD）的开发和临床研究，以填补我们的临床医疗设备的明显差距。充血性心力衰竭机械辅助治疗的随机评价（REMATCH）试验最近表明，与药物管理的患者相比，LVAD接受者的生存率和生活质量获益显著。然而，该试验还记录了与LVAD治疗相关的其余严重不良事件，如果克服这些不良事件，将大大增加其有效性，同时降低成本。 拟定的SCCOR旨在阐明和调节植入的长期机械循环支持器械与终末期心力衰竭患者之间界面的生物学。计划将密切相关的动物模型和人体临床试验相结合。研究将评估针对该界面导致的感染和凝血障碍的不良影响的新型干预措施。此外，将探索通过细胞移植改善自体心肌功能以促进器械取出的可行性。虽然观察和干预措施将集中在终末期心力衰竭，但在这种情况下对凝血的探索可以加强干预措施，以预防和管理出血和血栓栓塞，而细胞移植的探索有可能改善治疗方法，以减轻严重程度的心力衰竭。计划中的感染研究对一般的假体植入物有更广泛的影响。

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is a highly prevalent and morbid condition. Randomized trials have shown that the one-year mortality in the subset of heart failure patients with refractory endstage disease ranges from 50 to 75%. Outcomes are worse than those for breast, colon and even lung cancer. Pharmacological treatment offers limited benefit to these patients while heart transplantation is severely limited by the shortage of human donors. Implantable left ventricular assist devices (LVADs) have been developed and clinically investigated in order to fill the obvious gap in our clinical armamentarium. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Trial recently demonstrated significant survival and quality of life benefit in LVAD recipients compared to medically managed patients. However, the trial also documented the remaining serious adverse events associated with LVAD therapy, which, if overcome, would add substantially to its effectiveness while reducing costs. The proposed SCCOR seeks to elucidate and modulate the biology of the interface between implanted long-term mechanical circulatory support devices and patients with end-stage heart failure. A combination of closely linked animal model and human clinical trials is planned. Studies will evaluate novel interventions directed at the adverse impact of infection and coagulopathy that result from this interface. Furthermore, the feasibility of improving native myocardial function through cellular transplantation in order to facilitate device removal will be explored. While observations and interventions will focus on end-stage heart failure, the exploration of coagulation in this setting could enhance interventions to prevent and manage bleeding and thrombo-embolism while exploration of cellular transplantation has the potential to improve therapeutic approaches to less severe forms of heart failure. The planned research on infection has broader implications for prosthetic implants in general.