Novel and Emerging Technologies (NET) Grant
Mr Steven Tsui, Papworth Hospital NHS Foundation Trust, Cambridge
There are not enough donor hearts for everyone that needs a heart transplant. This project will test whether a combination of machine perfusion before and after donor heart retrieval can restore the function of donor hearts that would otherwise be rejected by transplant teams. If proven to work, this approach would increase the numbers of suitable donor hearts available so that more patients with severe heart failure can benefit.
It is almost 50 years since the first successful human heart transplant and it remains the gold standard treatment for severe heart failure. The increasing demand for heart transplants, however, vastly outstrips the limited number of usable donor hearts. In 2014/15, there were 547 patients in the UK on the heart transplant waiting list but only 180 heart transplants were carried out.
Worryingly, less than 3 in 10 of all the donor hearts made available from ‘donation after brain death’ (DBD) are transplanted. This is due mainly to the harmful effects of brain death on the donor heart leaving it too damaged to be transplanted.
The aim of this project is to limit the injury to donor hearts after brain death, so that more are available for transplantation. This would give more patients on the heart transplant waiting list the chance to undergo this life-saving operation.
How the donor heart gets damaged:
The process of brain death in the donor has many harmful effects on the heart. Also, in order to maintain an adequate blood flow to the other vital organs in the donor, intensive care doctors often have to use powerful drugs to drive these already injured hearts to work harder. This causes further damage.
After a donor heart has been removed from the body of the donor, it is placed in a ‘cool box’ packed with ice and transported to the recipient hospital to be transplanted. The heart receives no oxygen during this time and deteriorates further. This makes it hard for the transplant surgeon to be confident that after it has been transplanted, the donor heart will function well enough to keep the recipient alive. In fact, as many as one in three of the carefully selected donor hearts that are transplanted go on to develop so-called ‘primary graft failure’. This is a devastating complication where the newly transplanted donor heart does not work properly and this is the leading cause of death in recipients during the early period after transplant surgery.
At Papworth Hospital in Cambridge, Mr Tsui and his team have recently set up a world-leading ‘donation after circulatory determined death’ (DCD) heart transplant programme. These DCD hearts are very different to DBD donor hearts in that they have suffered even more damage and have already arrested in the donor. Over the decades, cardiac surgeons have dismissed the possibility of transplanting hearts from DCD donors. By using a mechanical circulatory support system, called ‘ECMO’, the team has been able to restore good function in a high proportion of DCD hearts. To avoid further injury to these carefully reconditioned DCD hearts during transportation, they are placed in a specially designed machine, instead of a cool box with ice. This technique is known as machine perfusion which provides the donor heart with warm blood enriched with oxygen and nutrients continuously.
This project will use the same approach to recondition and retrieve injured DBD hearts that are rejected by transplant teams. By using ECMO to provide blood flow to vital organs in the DBD donors, the need to use powerful drugs to drive the donor heart might be avoided while allowing the injured donor hearts to rest and recover. Once retrieved from the donor body, machine perfusion will maintain the recovering DBD hearts during transportation to avoid further injury.
This exciting research may lead to better use of valuable donor hearts, fulfilling the wishes of more donors and their families who have generously offered organs for transplantation. Above all, it would give more patients who are dying from severe heart failure the chance of a life-saving heart transplant.