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

总结/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， 每年有100万新病例报告。虽然心脏移植是最好的治疗选择， 许多病人，每年全球进行的手术不到6 000例。因此，估计 50，000 - 100，000名患者可以立即受益于机械循环支持。 许多循环支持装置可用于需要左心室支持的患者，但选择很少 适用于受益于双心室支持的患者。除了移植，最佳的 治疗双心室衰竭的方法是用全人工心脏（TAH）替换自体心脏。 传统的方法使用容积式泵，容积式泵具有固有的局限性，这是由于容积式泵的缺点。 大尺寸、柔性膜和阀门共同降低了装置的耐用性和寿命。的 在VAD技术的早期应用中，也观察到了同样的局限性，这促使了一种过渡 涉及用于减小尺寸和增加耐用性的旋转血泵。今天，超过6万名患者 支持旋转VAD。利用旋转血泵技术的优势，BiVACOR TAH体积小，可靠，血液友好，具有固有的平衡血流。 在之前的SBIR II中，BiVACOR TAH的植入式组件得到显著改善， 在实验台上和体内验证。在血液相容性、生理学和生物学方面取得了显著进展， 相互作用、解剖学拟合和可靠性。BiVACOR目前正在进入最终产品开发阶段， 制造阶段，并希望利用SBIR IIB计划准备BiVACOR TAH系统用于首次 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， 具体目标将完成：1）生产临床级TAH系统; 2）验证和确认， 包括在药物非临床研究质量管理规范环境下进行的体内研究，以获得监管批准;以及3） 提交EFS监管文件。该产品的商业应用和可行性将是 这将得到证明，并将鼓励为全面商业化进行额外投资。 一种商业上可行的、长期的人类心脏衰竭的机械替代物的全球影响 将会是巨大的。迫切需要心脏移植的病人的等待时间将从几年到几年。 货架可用性，从而迅速提供大大改善的生活质量。利用成功的耐久性 用于BiVACOR旋转TAH心室辅助的小型类似技术提供了 有希望的途径，最终实现一个可靠的，生物相容性，生理，并最终实用的目标， 来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.