BiVACOR - A Physiological, Durable and Blood-Friendly Total Artificial Heart

摘要/摘要 心力衰竭(HF)是一种毁灭性的流行病，影响着全球2300多万患者；仅在美国， 每年报告的新病例有100万例。虽然心脏移植提供了最好的治疗方案 许多患者，每年在全球范围内进行的手术不到6000例。因此，据估计， 50,000-100,000名患者可以立即从机械循环支持中受益。 对于需要左心室支持的患者，有许多循环支持设备可用，但选择很少 存在于将从双心室支持中受益的患者。除了移植，最优的 治疗双心衰的方法是用全人工心脏(TAH)替代天然心脏。 传统的方法使用体积排量泵，由于其本身的局限性，这种泵具有固有的局限性 大尺寸、可弯曲的薄膜和阀门，这些都会降低设备的耐用性和寿命。这个 在VAD技术的早期应用中也观察到了同样的限制，这促使了过渡 旋转式血泵的体积缩小和耐用性提高。今天，超过6万名患者 由旋转式VAD支持。利用旋转式血泵技术的优势，BiVACOR TAH体积小，可靠，对血液友好，具有天生的平衡血液流动。 在之前的SBIR II中，BiVACOR TAH的可植入部件得到了显著改进和 在台式机和体内进行了验证。在血液相容性、生理方面取得了显著的进步 相互作用，解剖学上的适合性和可靠性。BiVACOR现在正在进入最终产品开发和 制造阶段，并希望利用SBIR IIB计划为BiVACOR TAH系统做好第一次准备 通过FDA批准的早期可行性研究(EFS)进行临床应用。为了实现这一目标，应采取以下措施 具体目标将完成：1)生产临床级别的TAH系统；2)验证和确认， 包括在良好的实验室实践环境下进行体内研究，以供监管部门批准；以及3) 提交EFS的法规文件。该产品的商业应用和生存能力将是 展示并将鼓励额外投资，以实现完全商业化。 一种商业上可行的长期机械替换对衰竭的人类心脏的全球影响 将是巨大的。等待迫切需要心脏移植的患者的时间将从数年延长到非常规的- 货架供应，从而迅速提供极大改善的生活质量。利用成功的耐用性 而体积较小的类似技术用于心室辅助的BiVACOR旋转式TAH提供了 最终实现可靠的、生物兼容的、生理的并最终实用的目标的有希望的途径 替代衰竭的人类心脏。

SUMMARY/ABSTRACT Heart Failure (HF) is a devastating epidemic affecting more than 23 million patients worldwide; in the U.S. alone, 1,000,000 new cases are reported each year. While heart transplantation provides the best treatment option for many patients, less than 6,000 procedures take place globally each year. Consequently, it is estimated that 50,000 – 100,000 patients could immediately benefit from mechanical circulatory support. Many circulatory support devices are available for patients who require left ventricular support, but few options exist for patients who would benefit from biventricular support. With the exception of transplantation, the optimal approach to biventricular failure is the replacement of the native heart with a Total Artificial Heart (TAH). Traditional approaches have used volume displacement pumps, which have inherent limitations due to their large size, flexing membranes, and valves that conspire to reduce the durability and lifetime of the device. The same limitations were observed throughout the early application of VAD technology, which prompted a transition to rotary blood pumps for size reduction and increased durability. Today, more than 60,000 patients are supported with rotary VADs. Capitalizing on the advantages of rotary blood pump technology, the BiVACOR TAH is small, reliable, blood-friendly and has inherently balanced blood flows. Under the previous SBIR II, the implantable components of the BiVACOR TAH were significantly improved and validated on the benchtop and in-vivo. Notable advancements were made in hemocompatibility, physiological interaction, anatomical fit and reliability. BiVACOR is now entering the final product development and manufacturing phase and wishes to utilize the SBIR IIB scheme to ready the BiVACOR TAH system for the first clinical application via an FDA-approved Early Feasibility Study (EFS). In order to achieve this goal, the following specific aims will be completed: 1) production of a clinical grade TAH system; 2) verification and validation, including in-vivo studies under a Good Laboratory Practice environment, for regulatory approval; and 3) submission of regulatory documentation for EFS. The commercial application and viability of this product will be demonstrated and will encourage additional investment for full commercialization. The world-wide impact of a commercially viable, long-term mechanical replacement to the failing human heart will be tremendous. The wait for patients desperately requiring a heart transplant will go from years to off-the- shelf availability, thereby quickly providing a vastly improved quality of life. Leveraging the successful durability and small size of similar technologies used for ventricular assistance into the BiVACOR rotary TAH provides a promising pathway to finally achieve the goal of a reliable, biocompatible, physiological, and ultimately practical replacement to the failing human heart.