Mechanical circulatory support devices have profoundly transformed the management of severe cardiothoracic disorders. While heart transplantation is the gold standard therapy for end-stage heart disease, long-term mechanical support devices are a viable alternative for those ineligible and/or those awaiting organ availability. Major technological advancements were made over first 5 decades of development, resulting in improved durability and survival with reduced adverse events. However, gains have tapered recently for various complications (e.g., internal bleeding, multisystem organ failure), which collectively represent a significant proportion of disability and/or mortality. Further, in light of mature ventricular assist devices failing during clinical trials or even after clinical approval (class I withdrawals), it is timely to consider: Are our preclinical assessment protocols vital in the design and development of mechanical circulatory support devices, providing a realistic and reliable profile of future clinical performance? This commentary explores this question and analyses development pathways through the lens of the various disciplines involved in the preclinical assessment of mechanical circulatory support technologies: Limitations in approaches to benchtop blood testing, computational design and simulation, and animal testing are discussed as likely contributors to some of the common hemocompatibility-related adverse events (HRAEs). While it is acknowledged that some shortcomings are pragmatic in nature, possible solutions are presented that will only be realized through truly transdisciplinary and open approaches that challenge the current nature of medical device development. We suggest that these can and must be overcome to diminish HRAEs and will potentially demarcate the fourth generation of cardiac assist devices.

中文翻译：

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血液知情设计是否标志着第四代心脏辅助设备？


机械循环支持装置深刻地改变了严重心胸疾病的管理。虽然心脏移植是终末期心脏病的金标准疗法，但对于不合格和/或等待器官可用性的人来说，长期机械支持装置是一种可行的选择。在开发的前 5 年中取得了重大技术进步，从而提高了耐用性和存活率，减少了不良事件。然而，最近各种并发症（例如内出血、多系统器官衰竭）的进展逐渐减少，这些并发症在残疾和/或死亡率中占很大比例。此外，鉴于成熟的心室辅助装置在临床试验期间甚至在临床批准后（I 类退出）失败，现在是时候考虑：我们的临床前评估方案是否对机械循环支持装置的设计和开发至关重要，为未来临床性能提供现实可靠的概况？本评论探讨了这个问题，并通过机械循环支持技术临床前评估所涉及的各个学科的视角分析了发展途径：讨论了台式血液检测、计算设计和模拟以及动物试验方法的局限性，这些可能是导致一些常见血液相容性相关不良事件 （HRAE） 的原因。虽然人们承认一些缺点本质上是务实的，但提出了可能的解决方案，这些解决方案只能通过真正的跨学科和开放的方法来实现，这些方法挑战了医疗器械开发的当前性质。 我们认为，这些可以而且必须克服以减少 HRAE，并有可能划定第四代心脏辅助装置的界限。