Development of a patient-specific predictive tool and a regulatory testing machine for transcatheter heart valve replacement

心血管疾病是全球主要的死亡原因，夺走的生命比所有形式的癌症加起来还要多。在加拿大，每四例死亡中就有一例死于心血管疾病。它是造成医疗负担的主要原因，每年给加拿大经济造成超过220亿美元的损失。心脏瓣膜病是最严重的心血管问题之一。直到最近，患有瓣膜疾病的高危患者除了外科主动脉瓣置换手术外别无选择，因为手术死亡率很高。经导管瓣膜置换术(TVR)是一种新兴的微创手术。虽然许多患者在TVR干预后经历了显著的改善，但对其他人来说，情况明显恶化。 因此，迫切需要一种预测工具，能够在实际干预之前评估每个患者的TVR干预场景，以避免不可逆转的后果。这种工具将预测干预措施的有效性，允许对可能的临床解决方案进行系统测试，从而实现干预措施的个性化。此外，TVR(和其他人造阀门)的制造商在将其设备投放市场之前，必须验证其设备的设计和耐用性。尽管TVR很重要，但目前还没有现实的监管TVR测试机。为了满足这些需求，我们将开发一个可用于两个目标的平台： 1.作为计划临床干预的预测性工具：该工具将能够以患者特定的方式测试TVR干预方案的效果，以纠正每个患者身体上的瓣膜疾病。 2.作为一台监管医疗设备测试机：这台机器可以通过在体外执行许多重要的体内评估例程来满足医疗设备公司的测试需求，并将显著减少对动物研究和人体试验的需求，因此它可以显著加快设备审批过程，并减少新设备的上市时间和成本。

Cardiovascular disease is the leading cause of death globally and claims more lives than all forms of cancer combined. In Canada, one in every four deaths is from cardiovascular disease. It is the leading cause of burden on healthcare costing the Canadian economy more than $22 billion every year. Valvular disease is one of the most serious cardiovascular problems. Until recently, high-risk patients with valvular disease had no other option than the surgical aortic valve replacement procedure, which has a high mortality rate. Transcatheter valve replacement (TVR) is an emerging minimally invasive device. While many patients experience a significant improvement after TVR intervention, for others the situation worsens significantly. Therefore, there is a crucial need for a predictive tool which has the capability of evaluating TVR intervention scenarios in each patient before the actual intervention to avoid irreversible consequences. Such tool would predict effectiveness of interventions, allowing systematic testing of possible clinical solutions, and thus enable personalization of interventions. Moreover, manufacturers of TVR (and other artificial valves) must validate the design and durability of their devices before releasing them to the market. Despite its importance, there exists no realistic regulatory TVR testing machine. To address these needs, we will develop a platform to be used for two objectives: 1. As a predictive tool for planning clinical interventions: The tool will have the capability testing of effects of TVR intervention scenarios for correcting valvular diseases on the body of each patient body in a patient-specific manner. 2. As a regulatory medical-device testing machine: This machine can serve testing needs of medical-device companies by making it possible to perform many important in vivo evaluation routines in vitro and will significantly reduce the need for animal studies and human trials so it can significantly speed up the device approval process and reduce the time-to-market and cost-to-market for new devices.