Apical Access System with Universal Connector for Beating Heart LVAD Implantation

描述（由申请人提供）：本提案旨在完成长期通用心尖入路系统（AAS）的开发，以改善临床结局并扩大左心室辅助装置（LVAD）治疗的作用。终末期心力衰竭（HF）的治疗是当今美国医疗保健系统在临床和经济上面临的最大挑战。每年有超过800，000人患有终末期HF，只有2，300例心脏移植和4，600例LVAD植入，存在大量服务不足的人群。LVAD植入需要大手术，具有显著的术中和术后出血并发症、死亡率和治疗费用。APK下载器APK下载器AAS系统将允许当前的LVAD和未来的“Mini-VAD”通过微创切口无缝合植入，而无需将患者置于心肺转流（CPB）。通过消除CPB、减少穿刺时间和减少出血，将对患者健康和手术成本产生显著且可衡量的影响。AAS系统的不同组件之前已在实验室、FEA计算模型以及急性和慢性（长达12周）动物实验中进行了测试，结果为阳性。当前提案的具体目标是：第I阶段-目标1：完成重新设计的AAS系统的集成组件的制造，并证明在急性牛模型（n=2）和人尸体（n=2）中进行LVAD治疗的可行性。第二阶段-目标1：根据人体植入物质量体系的良好生产规范（GMP）规范，完成LVAD AAS的工程开发和设计冻结。目的2：通过完成风险分析驱动的确认和验证测试，证明AAS系统的安全性和有效性。测试包括：6亿次循环疲劳、加压心脏中的泄漏/爆破试验、锚定组件的有限元分析、灭菌确认和生物相容性、解剖结构匹配和外科手术研究（人体尸体，n=8）以及使用HM II（Thoratec）和HVAD（HeartWare）器械在慢性牛模型中进行的体内急性（n =6）、14天（n=6）和30天（n=6）试验。成功结局将通过指标进行量化，包括：切口尺寸、易用性、植入时间、失血量、耐久性（临床级组件疲劳）、CPB需求、符合生物相容性和灭菌ISO标准以及牢固连接，无空气夹带或泄漏。目标3：在30天GLP前（n=2）和GLP（n=4）慢性牛模型研究中证明LVAD AAS的长期安全性和可靠性，以支持仅接受LVAD植入的晚期心力衰竭患者临床试验的IDE申请。该SBIR项目的成功执行将导致HF治疗中新的临床范例的开发。具体而言，AAS将降低手术复杂性，并使LVAD治疗负担得起，从而改善患者结局和生活质量。最终，可以实现治疗早期HF患者的临床接受度并扩展到全球市场。

DESCRIPTION (provided by applicant): The objective of this proposal is to complete development of a long-term, universal Apical Access System (AAS) to improve clinical outcomes and expand the role of left ventricular assist device (LVAD) therapy. The treatment of end stage heart failure (HF) is the greatest challenge, both clinically and economically to the U.S. health care system today. With >800,000 people suffering with end stage HF and only 2,300 heart transplants and 4,600 LVADs implanted annually there is large a population underserved. LVAD implantation requires a major operative procedure with significant peri- and post-operative bleeding complications, mortality, and treatment costs. APK Advanced Medical Technologies, Inc. AAS System will allow current LVADs and future "Mini-VADs" to be implanted suture-less through a minimally invasive incision without placing the patient on cardiopulmonary bypass (CPB). By eliminating CPB, reducing access time and reducing bleeding, a significant and measurable impact on patient health and procedural cost will be achieved. The different components of the AAS System have been tested previously on the bench, in FEA computational models, and through acute and chronic (up to 12 weeks) animal experiments with positive results. The specific aims of the current proposal are: Phase I-Aim 1: Complete fabrication of the integrated components for the re-designed AAS System and demonstrate feasibility for LVAD therapy in acute bovine model (n=2) and human cadaver (n=2). Phase II-Aim 1: Complete the engineering development and design freeze of the LVAD AAS in compliance with Good Manufacturing Practices (GMP) specifications for a human implant quality system. Aim 2: Demonstrate safety and efficacy of the AAS System by completing risk analysis driven validation and verification testing. Testing to include: 600 Millio cycle fatigue, leakage/burst testing in pressurized hearts, Finite element analysis of anchoring components, sterilization validation and biocompatibility, anatomical fit and surgical procedure study (human cadaver, n=8), and in vivo acute (n=6), 14-day (n=6), and 30-day (n=6) in a chronic bovine model with HM II (Thoratec) and HVAD (HeartWare) devices. Successful outcomes will be quantified by metrics to include; incision size, ease of use, implantation time, blood loss, durability (fatigue on clinical-grade components), need for CPB, conformance to biocompatibility and sterilization ISO standards, and secure connection without air entrainment or leakage. Aim 3: Demonstrate long-term safety and reliability of the LVAD AAS in 30-day pre-GLP (n=2) and GLP (n=4) chronic bovine model study to support an IDE application for a clinical trial in patients with advanced heart failure receiving LVAD implantation only. The successful execution of this SBIR project will lead to development of a new clinical paradigm in the treatment of HF. Specifically the AAS will reduce surgical complexity and make LVAD therapy affordable leading to improved patient outcomes and quality of life. Ultimately, clinical acceptance to treat earlier stage HF patients and expansion into global markets can be achieved.