Apical Access System with Universal Connector for Beating Heart LVAD Implantation

描述(由申请人提供)：这项提案的目标是完成长期、通用心尖接入系统(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面临的最大挑战，无论是在临床上还是在经济上。有80万人患有晚期心力衰竭，每年只有2300例心脏移植和4600例左心室反搏，有很大一部分人得不到充分的服务。LVAD植入术需要一个大的手术过程，手术前后有显著的出血并发症、死亡率和治疗费用。APK先进医疗技术公司的AAS系统将允许通过微创切口无缝合地植入当前的LVAD和未来的“迷你VAD”，而无需将患者置于体外循环(CPB)。通过取消体外循环、减少入院时间和减少出血，将对患者的健康和程序成本产生显著和可衡量的影响。AAS系统的不同组件之前已经在工作台上、有限元分析计算模型中以及通过急性和慢性(长达12周)的动物实验进行了测试，结果均为阳性。目前方案的具体目标是：第一阶段-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)和人身体(n=2)上证明LVAD治疗的可行性。第二阶段-目标1：按照人体植入物质量系统的良好制造规范(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验证和验证测试，展示AAS系统的安全性和有效性。测试包括：600Millio循环疲劳，加压心脏泄漏/爆裂测试，锚固部件的有限元分析，灭菌验证和生物兼容性，解剖适合性和手术程序研究(人体身体，n=8)，以及使用HM II(Thoratec)和HVAD(HeartWare)设备的在体急性(n=6)、14天(n=6)和30天(n=6)牛模型。成功的结果将通过量化指标进行量化，包括：切口大小、易用性、植入时间、失血量、耐用性(临床级部件疲劳)、是否需要体外循环、是否符合生物兼容性和灭菌ISO标准，以及安全连接而不夹带空气或渗漏。目的3：在GLP前30天(n=2)和GLP(n=4)慢性牛模型研究中，证明了LVAD AAS的长期安全性和可靠性，以支持将IDE应用于仅接受LVAD植入的晚期心力衰竭患者的临床试验。这一SBIR项目的成功实施将导致开发一种新的治疗心力衰竭的临床范例。具体地说，AAS将降低手术复杂性，并使LVAD治疗负担得起，从而改善患者的预后和生活质量。最终，可以实现临床接受治疗早期心力衰竭患者并扩展到全球市场。

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.