There is an urgent need for novel approaches to recovery, preservation and distribution of pediatric donor hearts in an effort to meet the growing demand. Continuous perfusion of donor hearts at normal body temperature has been proposed as a method for optimal preservation of heart function, but also as a method to recover and assess poorly functioning donor hearts so that they could also be used for life-saving transplants. The potential impact of this technology has not been previously examined in the pediatric population, nor have the attitudes of clinicians towards this ground breaking technology. The only commercially available device is not suited for pediatric hearts, thus there is a need for device and method development as well. Our project will examine all three of these issues: feasibility, attitudes and device. We have extensive experience with experimental donor heart preservation using continuous perfusion at room temperature, and therefore are optimally positioned to accomplish the work that has been proposed.

Aim 1: Understand pediatric heart transplant stakeholders’ perspective towards ESHP.

Aim 2: Analyze UNOS data to identify the frequency and reason for organ non-use.

Aim 3: Develop and test an ESHP device that can be used for neonatal to pediatric sized donor hearts.

There is a widening gap between donor organ availability and recipient demand for pediatric heart transplantation. This is compounded by the fact that less than 50% of available hearts are utilized. The primary reasons for non-use included projected long ischemic time, poor donor function, size and blood/HLA mismatch. Increasing utilization is important not only to increase the option for a potential recipient but to decrease waitlist mortality as refusal of a donor heart that is later accepted by another program is associated with a higher waitlist mortality. Ex vivo or ex situ organ perfusion (ESHP) is a method for continuous perfusion of the donor heart, allowing extended outof-body time as well as functional assessment of the organ prior to implant. While there are a number of factors that are considered during the process of evaluating a donor, two particular factors including the function of the donor heart and the distance between the donor center and the transplant center can be potentially mitigated by ESHP. A recent survey of practitioners found that hearts were turned down based on function when the ejection fraction was typically below 50%(1). ESHP would allow for further time to reassess donor function and potentially introduce therapies to improve function. In addition to donor quality, projected ischemic times, including the time to travel, may be a reason for lack of donor utilization. It is well known that the ideal ischemic time for a pediatric donor is less than 4 hours for optimal outcomes at 1, 5 and 10 years posttransplant (ref). This time constraint may be improved by ESHP as it would allow for a longer period of time between organ procurement and transplant without the donor heart sustaining ischemic damage and therefore this could result in an increase in the utilization of donor organs. Ex-situ machine perfusion of organs for transplantation is not a new concept. It has previously been shown that post-transplant kidney function can be improved with machine perfusion, and that this translates to improved clinical outcomes (2). Lung transplant programs across the country, including our own, have been instrumental in demonstrating that ex vivo lung perfusion (EVLP) allows assessment and treatment of marginal lungs from brain dead (BD) donors and lungs from donors after circulatory death (DCD)(3–9). This work has also demonstrated that lungs can be maintained ex vivo for up to 12 hours without sacrificing function, and that indeed function can be improved(10–12). This represents a paradigm shift in the assessment of donor organs: Whereas previously physicians were forced to determine the suitability of organs as they existed in the donor, with the attendant adverse milieu, now physicians have the opportunity to explant organs and perform investigations and interventions ex vivo, in an effort to maximize the number and function of organs that are available for transplantation. Although interest in ESHP technology has grown over the past several years, clinical adoption in adult heart transplant has remained low despite the availability of an investigational device. The Transmedics Organ Care System is the only clinically available system, but it is restricted to use in adult-sized hearts, and cannot be adapted for use in small pediatric or neonatal hearts. Therefore, there is a need for device development to allow the application of ESHP to the pediatric donor heart pool to potentially increase the use of donor hearts. This effort, requires the development of an appropriate device, a clear understanding of the potential impact and an assessment of the attitudes towards ESHP in the pediatric heart transplant community. These points will be addressed in this current study by focusing on the following objectives:

1) Understand pediatric heart transplant stakeholders’ perspectives on ESHP and potential barriers that will need to be overcome to support widespread adoption of the technology.

2) Analyze UNOS data to identify the frequency and reason for organ non-use and utilize donor location to estimate the number of potential sites a donor could be offered to due to ESHP.

3) Develop and test of an ex situ heart perfusion device capable of continuous perfusion of the donor heart at subnormothermic temperature