Narrowing the gap between supply and demand in heart transplantation

项目概要/摘要 在美国，心脏移植（HT）的需求远远超过了 捐献器官。每年，等待名单上的500多名患者死亡或病情过重， 移植高致敏水平患者的结局尤其差- 预先形成的抗体的存在使得一个人与潜在的供体不相容。减少 等待名单的死亡率，缩小供体心脏供需之间的差距至关重要， 维护公平。目前的研究将为在一系列三个目标中这样做的努力提供信息。 第一个目的是显示更高的供体心脏利用率的可行性和益处， 即用于移植的候选心脏的比例。平均供体心脏 在美国的使用率约为30%。在欧洲和更“积极”的中心，利用率更高 在美国，尽管如此，移植后的结果还是可以接受的。当前 研究将使用模拟建模来评估假设的场景，其中所有美国HT中心 实现与1）“积极”的美国中心和2）欧洲中心相同的利用率。成果 感兴趣将包括等待时间和生存，在人口一级衡量。 第二个目标是确定哪些患者会受益于 移植正在测试的假设是，等待名单上的许多人会表现得一样好或更好 用药物或机械装置治疗代替移植。将这些患者除名将 有助于缓解供需缺口，但确定这一子集具有挑战性。一种方法 使用多变量风险评分来衡量患者从移植中的潜在获益。的 目前的研究将系统地测试HT后生存评分的可靠性， 同伙怀疑他们的可靠性是穷人，一个替代的方法将被提出： 用血型作为工具变量来估计移植的好处。 第三个目的是证明优先考虑致敏患者的好处。 分配方案可以设计为提高优先级并减少敏感的等待时间。 患者在等待时间和人口水平的生存方面，这些计划的回报将 将使用模拟建模进行估计，并确定最佳优先级方案。 这项工作将在著名的研究机构斯坦福大学进行， HT研究领导者的家。它伴随着一个培训计划，利用密切的指导 以及斯坦福大学充足的资源，为学员提供相关的职业发展技能。

Project summary/abstract Demand for heart transplant (HT) in the United States (US) far exceeds the supply of donor organs. Each year, more than 500 patients on the waitlist die or become too sick for transplant. Outcomes are especially poor for patients with high levels of sensitization – the presence of preformed antibodies rendering one incompatible with potential donors. To reduce waitlist mortality, it is essential to narrow the gap between donor heart supply and demand while maintaining fairness. The current study will inform efforts to do so in a series of three aims. The first aim is to show the feasibility and benefits of higher donor heart utilization, that is, the proportion of candidate hearts that are used for transplant. Average donor heart utilization in the US is ~30%. Utilization is higher in Europe and at more “aggressive” centers within the US, who nonetheless achieve acceptable post-transplant outcomes. The current study will use simulation modeling to evaluate hypothetical scenarios in which all US HT centers achieve the same utilization rates as 1) “aggressive” US centers and 2) Europe. Outcomes of interest will include wait times and survival, measured on a population-level. The second aim is to identify patients who would – and would not – benefit from transplant. The hypothesis being tested is that many on the waitlist would fare as well or better with medical or mechanical device therapy in lieu of transplant. Delisting such patients would help alleviate the supply-demand gap, but identifying this subset is challenging. One approach uses multivariate risk scores to measure a patient’s potential benefit from transplant. The current study will systematically test the reliability of post-HT survival scores in historical cohorts. Suspecting their reliability to be poor, an alternative approach will be presented: to estimate the benefit to transplant using blood type as an instrumental variable. The third aim is to demonstrate the benefits of prioritizing sensitized patients. Allocation schemes can be designed that boost priority and reduce waiting times for sensitized patients. The payoff to such schemes, in terms of wait times and population-level survival, will be estimated using simulation modeling and an optimal prioritization scheme will be identified. This work will be conducted at Stanford University, a renowned research institution and home to leaders in HT research. It accompanies a training plan that draws on close mentorship and Stanford’s ample resources to equip the trainee with pertinent and career-advancing skills.