Development of SVAD System for HF Therapy

描述(由申请人提供)：这项提案的目标是完成SCR SVAD系统的工程开发和临床前测试，以便为不太晚期的心力衰竭(HF)患者提供部分心脏辅助。心力衰竭在全球范围内不断增加，在卫生保健资源和成本方面是一个主要负担。尽管医疗护理取得了进步，但心力衰竭的预后仍然很差，尤其是在晚期。目前，它需要主要的手术干预和体外循环(CPB)，这与显著的不良事件发生率和长时间的恢复有关。干预和患者随访的高昂成本限制了人们的广泛接受。SVAD系统包括一个微型轴流泵(铂合金叶轮和叶片扩散器)，流入左心房的导管，以及流出的移植物与腋动脉吻合。经右侧小切口植入长6 cm、直径2 cm、体重40g的SVAD泵。SVAD的临床好处包括：省去了大手术(胸骨切开)、LV心尖取心和主动脉吻合术；无需体外循环(非体外循环)；将泵放置在锁骨下口袋便于植入(和植入物)操作(S)；以及卓越的流体动力性能(5 LPM@100 mm Hg)和低功率要求。在这个I-II阶段的提案中，我们将展示SVAD的可行性和完整的工程开发和临床前测试，以支持FDA提交的第一阶段(n=10)和第二阶段(n=300)临床试验。为了实现这一目标，我们将完成SVAD系统的工程开发和设计冻结，并采用人体植入质量系统的良好制造规范(GMP)规范；通过完成验证和验证(V&V)测试(疲劳)、解剖匹配和手术程序研究(人体身体，n=4)以及体内急性(n=4)、慢性7天(n=6)和慢性45天(n=8)良好实验室实践(GLP)研究来展示有效性和生物兼容性。临床前、V&V、GMP和GLP研究数据将用于支持在心力衰竭患者中进行临床试验的IDE应用。我们的长期目标是 临床上将SCR SVAD转化为治疗早期心力衰竭患者，使用微型化的部分支持设备，以及侵入性较小的手术工具和程序，以改善患者预后和恢复生活质量。

DESCRIPTION (provided by applicant): The objective of this proposal is to complete the engineering development and pre-clinical testing of the SCR SVAD system to provide partial cardiac assist in patients with less advanced stage heart failure (HF). HF is increasing worldwide and represents a major burden in terms of health care resources and costs. Despite advances in medical care, prognosis with HF remains poor, especially in advanced stages. Currently, it requires a major operative intervention and cardiopulmonary bypass (CPB), which have been associated with significant adverse event rates and long recovery. The high cost of the intervention and patient follow-up has limited widespread acceptance. The SVAD system consists of a miniaturized axial flow pump (platinum alloy impeller and vane diffuser), inflow cannulation to the left atrium, and outflow graft anastomosis to axillary artery. The SVAD pump (6 cm length, 2 cm diameter, 40 g weight) is implanted through a right lateral mini-thoracotomy. The clinical benefits of the SVAD include: eliminates major surgery (sternotomy), LV apical coring, and aortic anastomosis; performed 'off pump' (no CPB); pump placement in subclavicular pocket facilitates implant (and explant) procedure(s); and superior hydrodynamic performance (5 lpm @ 100 mmHg) with low power requirements. In this phase I-II proposal, we will demonstrate feasibility and complete engineering development and pre- clinical testing of the SVAD to support a FDA submission for phase one (n=10) and phase two (n=300) clinical trials. To achieve this objective, we will complete the engineering development and design freeze of the SVAD system with Good Manufacturing Practices (GMP) specifications for a human implant quality system; demonstrate efficacy and biocompatibility by completing Validation and Verification (V&V) testing (fatigue), anatomical fit and surgical procedure study (human cadaver, n=4), and in vivo acute (n=4), chronic 7-day (n=6), and chronic 45-day (n=8) Good Laboratory Practices (GLP) study. The pre-clinical, V&V, GMP, and GLP study data will be used to support an IDE application for a clinical trial in HF patients. Our long-term goal is to clinically translate the SCR SVAD to treat earlier stage HF patients, using miniaturized partial support device, and less invasive surgical tools and procedures to improve patient outcomes and restore quality of life.