Optimizing donor hearts through machine perfusion

Improving the quality of experimental donor hearts by optimizing machine perfusion of the heart

Cardiac failure (CF) is an epidemic disease, affecting 26 million people worldwide. For patients with end-stage CF heart transplantation is the golden standard, but the availability of donor hearts is limited. Until recently, heart donation was only possible in brain death donors. Using heart perfusion outside the body (Ex-Situ Heart Perfusion [ESHP]), donor hearts can also become available from Donation in Circulatory Death [DCD] donors, which may potentially double the donor pool. Increasing the donor pool will have a positive effect on survival, quality of life and the contribution to the economic process of patients with end-stage CF. Also, a drop in the use of very expensive assist devices can be achieved and organ quality before transplantation can be improved which reduces the risk of complications, which all result in a cost reduction. Since the budget for health care costs in the Netherlands is frozen, reducing the cost of treatment while generating better outcomes is beneficial for our society. XVIVO perfusion is a company with extensive experience in organ perfusion, although the optimal perfusion approach for the heart has to be established. UMC Utrecht contributes their experience in heart donation, transplantation and regeneration. Together we can determine the optimal approach with regard to temperature, perfusion solution, driving pressure, oxygen fraction and type of oxygen carrier to use DCD hearts through ESHP. The main goal is to develop an ESHP protocol with 24-hour perfusion after DCD donation which does not result in significant cardiac injury or dysfunction during the ESHP interval and provide a platform for regenerative therapy. An experimental DCD heart donation setup is used with slaughterhouse pig hearts and experimental mice hearts. The end result of this project is an optimal perfusion approach of DCD hearts that can be directly implemented in the clinical setting.

Heart failure is a growing health problem that affects an increasing number of people. For patients with severe heart failure, a heart transplant is often the only treatment option. Unfortunately, there are not enough donor hearts available. Until recently, only hearts from brain-dead donors could be used for transplantation. Thanks to a new technique that keeps the heart warm and supplied with oxygen outside the body, it is now possible to also use hearts from donors who died after circulatory arrest. More available donor hearts mean that more patients can receive a life-saving transplant, improving both survival and quality of life. This project was a collaboration between the University Medical Center Utrecht (UMC Utrecht) and the company XVIVO, combining expertise in heart transplantation and organ preservation.

Heart failure is a significant cause of illness and death globally. In the Netherlands alone, over 250,000 individuals live with heart failure, and this number is anticipated to rise due to an aging population. Heart transplantation is a highly effective treatment; however, every year, many patients die while awaiting a suitable donor organ. Innovation is crucial for expanding the donor pool and reducing waiting times.

In this project, researchers developed a method to preserve hearts from circulatory death donors for up to 24 hours outside the body under oxygenated conditions. This approach was tested using pig hearts, which are similar in size and function to human hearts. The hearts remained in good condition during preservation and could be successfully transplanted afterwards. The study also revealed new insights into the biological changes that occur in the heart during preservation. These findings help identify biomarkers that can be utilized in clinical settings to select donor hearts of the highest quality. This innovation paves the way for safer and more widely available heart transplantation

Summary
Patients with end-stage cardiac failure are best treated by a heart transplantation, but the availability of donor hearts is limited. The donor pool can be enlarged by using hearts from Donation after Circulatory Death donors in combination with machine perfusion of the heart which will be optimized in this project.
Technology Readiness Level (TRL)
2 - 4
Time period
43 months