Transcatheter Device for Congestive Heart Failure Treatment Through Left Atrial Decompression

摘要 充血性心力衰竭（CHF）是一种慢性进行性疾病，目前影响超过600万患者 在美国.它占每年医疗保健支出超过350亿美元，并负责超过100万美元， 每年住院。CHF是一种慢性进行性疾病，心脏无法泵血 足够的血液来维持足够的循环-心脏无法满足身体的需要。的预后 这些患者是穷人：尽管最好的药物治疗，患者有5年和10年 死亡率分别为50%和90%。发病率高，患者通常表现出以下症状： 呼吸困难、运动不耐受和最小用力时的疲劳。虽然现有的药理学 治疗已经证明在患有心力衰竭的患者中症状改善和死亡率获益， 射血分数降低目前FDA批准的治疗选择有限（药物或装置， 基于）用于射血分数保留的心力衰竭患者人群。最近，心房间隔的概念 分流术作为CHF患者的潜在治疗选择已受到关注。通过建立联系 在高压左心房与低压右心房之间，升高的左心房压力（LVEF）可以是 有效降低从而缓解CHF症状。最近，几种可植入的心房间分流装置已经 已被证明能够使左心房到右心房的血流，导致左心房减压，减少CHF 症状，并在许多有前途的人类临床研究中改善生活质量。尽管如此， 植入物具有已证实的临床风险，包括凝块形成装置断裂、迁移和植入失败。 目前没有可用的设备可以提供治疗性左心房减压而不需要长时间的- 长期临床风险和在心脏中留下异物的担忧。我们认为没有植入物的选择 这是可以实现的，应该为广大患者提供。Alleviant Medical开发了一种新的 经导管方法通过建立房间分流来减轻左心房压力，而无需心脏 植入第一阶段用于迭代设计、开发和确定新型导管系统的可行性 用于创建可重现和稳定的心房间分流，如在实验室、急性和慢性 动物研究。在第二阶段，我们将优化剩余的设计元素， 验证和确认测试，并进行GLP慢性动物研究，以证明器械可靠性， 安全性、分流耐久性和生物相容性符合临床、法规和产品开发要求 目标.第一个目标是在测试之前完成最终设计优化。第二个目标是引导 FDA批准IDE提交的设计验证测试。第三个目标是完成GLP慢性动物 FDA批准IDE申请的研究。成功执行本计划中概述的工作将产生 FDA关键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.