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.