Transcatheter Device for Congestive Heart Failure Treatment Through Left Atrial Decompression

摘要 充血性心力衰竭(CHF)是一种慢性进展性疾病，目前影响着600多万患者 在美国。它每年的医疗支出超过350亿美元，并负责100多万 每年住院治疗的人数。充血性心力衰竭是一种慢性进行性疾病，心脏不能泵血。 足够的血液来维持充足的循环--心脏不能满足身体的需要。脑血管疾病的预后 这些患者很穷：尽管有最好的药物治疗，但患者有5年和10年的 死亡率分别为50%和90%。发病率很高，患者通常表现出 气喘吁吁，运动不耐受，以及最低限度的劳累。虽然现有的药理学 治疗显示心力衰竭患者的症状改善和死亡率增加 减少射血分数目前FDA批准的治疗选择有限(药物或设备- 对于射血分数保持不变的心力衰竭患者群体。近年来，关于房间隔的概念 分流术作为治疗充血性心力衰竭患者的一种潜在的治疗方法，已经引起了人们的关注。通过创建连接 在高压左房与低压右房之间，左房压力升高(LAP)可能 有效降低心衰症状，从而缓解心力衰竭症状。最近，几个可植入的房内分流装置已经 已被证明能够使左房到右房的血液流动，导致左房减压，减少心力衰竭 在一些有希望的人类临床研究中，患者的症状和生活质量得到了改善。尽管如此，心内直视手术 植入物具有已证实的临床风险，包括血栓形成装置断裂、移位和植入失败。 目前还没有可用的设备可以提供治疗性左房减压而不需要长时间的 长期临床风险和在心脏中遗留异物的担忧。我们认为不植入的选择是 是可以实现的，应该为广大患者提供。Alleviant医疗公司开发了一种新的 经导管建立房内分流减轻左房压力的方法 植入。第一阶段用于迭代设计、开发和建立新型导管系统的可行性 用于建立可重复和稳定的房间分流，如台式、急性和慢性 动物研究。在第二阶段，我们将对剩余的设计元素进行优化，完成详尽的性能 验证和确认测试，并进行GLP慢性动物研究，以证明设备的可靠性， 安全性、分流耐用性和生物兼容性符合临床、法规和产品开发 目标。第一个目标是在测试前完成最终设计优化。第二个目标是进行 FDA Pivotal IDE提交的设计验证测试。第三个目标是完成GLP慢性动物 FDA Pivotal IDE提交的研究报告。成功执行本计划中概述的工作将产生 FDA Pivotal IDE提交的系统设计和数据集以及临床和商业进展 努力。

ABSTRACT Congestive heart failure (CHF) is a chronic and progressive condition that currently affects over 6 million patients in the US. It accounts for over $35B in annual healthcare expenditure and is responsible for over one million hospitalizations each year. CHF is a chronic and progressive condition in which the heart is unable to pump enough blood to maintain adequate circulation - the heart is failing to meet the body’s needs. The prognosis for these patients is poor: despite best available pharmacological therapy, patients have 5-year and 10-year mortality rates of 50% and 90%, respectively. Morbidity is high and patients commonly exhibit symptoms of breathlessness, exercise intolerance, and fatigue upon minimal exertion. Although existing pharmacological therapies have demonstrated symptomatic improvement and mortality benefit in patients with heart failure with reduced ejection fraction there are currently limited FDA-approved treatment options (pharmacological or device- based) for the heart failure with preserved ejection fraction patient population. Recently the concept of interatrial shunting has gained attention as a potential therapeutic option for patients with CHF. By creating a connection between the high-pressure left atrium to the low-pressure right atrium elevated left atrial pressure (LAP) may be effectively lowered thereby relieving CHF symptoms. Recently, several implantable interatrial shunt devices have been shown to enable left atrial to right atrial blood flow, resulting in left atrial decompression, a reduction in CHF symptoms, and improved quality of life in a number of promising human clinical studies. Nonetheless intracardiac implants carry proven clinical risks including clot formation device fracture, migration, and implantation failure. There is currently no device available that can provide therapeutic left atrial decompression without the long- term clinical risks and concerns of leaving behind a foreign body in the heart. We believe a no implant option is achievable and should be provided for the vast number of patients. Alleviant Medical has developed a novel transcatheter approach to relieve left atrial pressure by creating an interatrial shunt without the need for a cardiac implant. Phase I was utilized to iteratively design, develop, and establish feasibility of a novel catheter system for the creation of a reproducible and stable interatrial shunt as demonstrated in benchtop, acute, and chronic animal studies. In Phase II, we will optimize remaining design elements, complete exhaustive performance verification and validation testing, and conduct a GLP chronic animal studies to demonstrate device reliability, safety, shunt durability, and biocompatibility consistent with clinical, regulatory, and product development objectives. The first aim is to complete final design optimization prior to testing. The second aim is to conduct design verification testing for an FDA Pivotal IDE submission. The third aim is to complete a GLP Chronic Animal study for an FDA Pivotal IDE submission. Successful execution of the work outlined in this program will yield a system design and dataset for an FDA pivotal IDE submission and progress towards clinical and commercial efforts.