Apical Access System with Universal Connector for Beating Heart LVAD Implantation

描述（由申请人提供）：本提案的目标是完成长期、通用的心尖通道系统（AAS）的开发，以改善临床结果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。每年只有2300例心脏移植和4600例左心室辅助装置被植入，而患有终末期心力衰竭的患者达80万人。LVAD植入需要一个大的手术过程，有明显的围手术期和术后出血并发症、死亡率和治疗费用。APK先进医疗技术有限公司AAS系统将允许目前的lvad和未来的“mini - vad”通过微创切口无缝线植入，而无需将患者置于体外循环（CPB）上。通过消除CPB、缩短就医时间和减少出血，将对患者健康和手术成本产生重大和可衡量的影响。AAS系统的不同组成部分已经在之前的实验台上进行了测试，在FEA计算模型中进行了测试，并通过急性和慢性（长达12周）的动物实验获得了积极的结果。当前提案的具体目标是：阶段1 -目标1：完成重新设计的AAS系统的集成组件的制造，并在急性牛模型（n=2）和人类尸体（n=2）中证明LVAD治疗的可行性。第二阶段-目标1：完成LVAD AAS的工程开发和设计冻结，符合人体植入物质量体系的良好生产规范（GMP）规范。目标2：通过完成风险分析驱动的验证和验证测试，证明AAS系统的安全性和有效性。测试包括：6亿次循环疲劳，加压心脏的泄漏/破裂测试，锚定部件的有限元分析，灭菌验证和生物相容性，解剖配合和手术程序研究（人类尸体，n=8），以及在HM II （Thoratec）和HVAD （heartare）装置的慢性牛模型中急性（n=6）， 14天（n=6）和30天（n=6）。成功的结果将通过以下指标进行量化：切口大小，易用性，植入时间，出血量，耐久性（临床级组件的疲劳），CPB需求，符合生物相容性和灭菌ISO标准，安全连接，无夹带空气或泄漏。目的3：在30天GLP前（n=2）和GLP前（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IDE应用于仅接受LVAD植入的晚期心力衰竭患者的临床试验。这个SBIR项目的成功实施将导致心衰治疗的新临床范例的发展。具体来说，AAS将降低手术复杂性，使LVAD治疗负担得起，从而改善患者的预后和生活质量。最终，临床接受治疗早期心衰患者和扩展到全球市场可以实现。

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.