DEVELOPMENT OF A PULMONARY FLOW RESTRICTOR FOR HYPOPLASTIC LEFT HEART SYNDROME

摘要 Starlight心血管公司正在开发一种将成为FDA批准的第一种经皮血流限制器来取代 先天性心脏病(CHD)，包括左心发育不良综合征(HLHS)的外科环扎术。这个 星光限流器的全球潜在市场价值超过2亿美元。 每年大约有1000名美国人出生时就患有左心发育不良综合征(HLHS)，这是一种疾病 左心室严重发育不全或几乎不存在。出生时患有HLHS的婴儿需要姑息 外科手术，通常是诺伍德手术，在出生后几天内为存活而进行，使新生儿接受 体外循环和昂贵的侵入性手术。一种混合性(半外科和半经皮)姑息疗法 手术作为一种选择而存在，然而混合手术的局限性是可靠的肺分支 动脉环扎术。分支肺动脉环扎术需要开放手术，可能会干扰肺动脉 动脉生长，需要进行肺动脉重建手术。尝试将现有设备修改为 创建经皮血流限制器来取代外科环扎术产生了一些有希望的临床结果。 然而，这些改进装置的使用受到诸如大和僵硬的输送系统等技术挑战的限制， 植入物长度长，缺乏可调性和可靠性，设计增加血栓形成的风险。 星光心血管公司正在开发一种经皮可调的分支肺动脉血流 替代外科捆扎的限制器。我们的设备解决了以前尝试在 经皮血流限制器，通过提供安全的静脉植入输送，可靠的血流减少，经皮 可调整性、有益的血流动力学，以及可拆卸的短且固定良好的植入物设计。这些 为HLHS设计的肺血流限制器也可以被修改以取代主肺动脉环扎术， 使可能受益的患者数量增加一倍以上。 这项第一阶段的SBIR资助将包括计算流体力学建模和测试，以告知设备 设计、台式机型号开发和最终设备设计选择通过最终用户台式机测试，由 儿科介入心脏病学家。该项目的成功完成将产生最终的设备设计， 已经为第二阶段的动物测试、设计改进以及验证和确认测试做好准备，这将 为临床试验准备限流装置，FDA人道主义装置豁免批准，以及 商业化。

ABSTRACT Starlight Cardiovascular is developing what will be the first FDA approved percutaneous flow restrictor to replace surgical banding in congenital heart defects (CHD), including Hypoplastic Left Heart Syndrome (HLHS). The potential worldwide market for the Starlight Flow Restrictor is over $200M. Approximately 1,000 Americans are born each year with Hypoplastic Left Heart Syndrome (HLHS), a condition where the left ventricle is severely underdeveloped or barely present. Babies born with HLHS require palliation surgery, commonly a Norwood procedure, within days after birth to survive, subjecting the neonate to cardiopulmonary bypass and a costly, invasive surgery. A hybrid (half surgical and half percutaneous) palliation procedure exists as an alternative, however a limitation of the hybrid procedure is reliable branch pulmonary artery banding. Branch pulmonary artery banding requires an open surgery and can interfere with pulmonary artery growth, necessitating pulmonary artery reconstruction surgery. Attempts at modifying existing devices to create percutaneous flow restrictors to replace surgical banding produced some promising clinical results. However use of these modified devices is limited by technical challenges such as large and stiff delivery systems, long implant lengths, lack of adjustability and reliability, and designs that increase thrombosis risk. Starlight Cardiovascular is developing a percutaneous and adjustable branch pulmonary artery blood flow restrictor to replace surgical banding. Our device addresses the shortcomings from previous attempts at a percutaneous flow restrictor, by providing safe venous implant delivery, reliable flow reduction, percutaneous adjustability, beneficial hemodynamics, and a short and well anchored implant design that is removable. These pulmonary flow restrictors designed for HLHS can be modified to also replace main pulmonary artery banding, more than doubling the number of patients who could benefit. This Phase I SBIR grant will consist of computational fluid dynamics modeling and testing to inform device design, benchtop model development, and final device design selection through end-user benchtop testing by pediatric interventional cardiologists. Successful completion of this project will produce a final device design that is ready for animal testing, design refinement, and Verification and Validation testing in Phase II, which will prepare the flow restrictor device for a clinical trial, FDA Humanitarian Device Exemption approval, and commercialization.