The time during which a donor organ is not supplied with blood during transport from the donor to the recipient is known as the ischaemia time and is a decisive factor for the success of a heart transplant. This is because of all the organs that can be removed from a deceased person for donation, the heart suffers the most rapid damage if it is not supplied with blood.
Until now, donor hearts have usually been flushed with a preservative solution at around four degrees Celsius and transported in cool boxes (‘static cold storage, SCS’). This minimises tissue damage. Nevertheless, the ischaemia time for donor hearts should not exceed four hours if possible. The choice of a suitable organ for people on the waiting list is therefore limited.
Development of the ‘HOPE’ system
A new system has been developed in Sweden that should largely remove the restrictions on organ transplants. The principle is known as ‘hypothermic oxygenated machine perfusion (HOPE)’ and consists of a transport device and a special preservation solution. The device - slightly larger than a moving box - contains a cooling system, a circulating pump and an oxygenator.
Before transport, the device is filled with a newly developed nutrient and preservative solution containing red blood cells, hormones, proteins and human albumin, among other things. After removal from the donor body, the heart is connected to the circulatory pump and continuously flushed with the solution during transport. The heart muscle cells are continuously supplied with fresh oxygen with the help of the oxygenator in the ‘heart box’. This circuit is cooled to a constant eight degrees Celsius for additional preservation of the organ.
Use in the international study
After extensive testing, the system was approved for use in humans as part of an international study and will be used for the first time in Germany at Deutsches Herzzentrum der Charité in autumn 2021.
In addition to the DHZC, 14 other centres from eight European countries took part in this study comparing ‘HOPE’ with static cold storage (SCS). A total of 229 patients were admitted between 25 November 2020 and 19 May 2023. Of these, 204 patients received a heart transplant and were included in the primary analysis.
Primary endpoint and results
The participants were randomly assigned to one of the two treatment groups. As the ‘primary endpoint’, i.e. the main factor for comparing the two methods, the researchers defined the occurrence of at least one of the following serious events within 30 days of transplantation: primary graft dysfunction (PGD, in simple terms, inadequate function of the donor organ immediately after transplantation), acute cellular rejection, graft failure or the death of the patient.
These serious events occurred in 19% of patients in the HOPE group compared to 30% in the SCS group, indicating a risk reduction of 44%. Particularly striking was the reduction in primary graft dysfunction, which occurred in 11% of patients in the HOPE group compared to 28% in the SCS group.
In addition, it was shown that other serious complications also occurred less frequently in the HOPE group: 65% of patients in this group reported such events, compared to 70% in the SCS group.
Evaluation and outlook
The results of the study, which have now been published in the British journal ‘The Lancet’, show that the HOPE method could represent a promising alternative to traditional static cold storage for the preservation of donor hearts.
DZHK scientist and heart surgeon Prof. Christoph Knosalla, the surgical head of the transplant programme at Deutsches Herzzentrum der Charité and - together with his DHZC colleague Dr Felix Hennig - one of the authors of the study, considers the results to be very encouraging: ‘The possibility of transporting donor organs without damage over significantly longer periods of time could significantly increase the number of donor organs available for our patients on the waiting list. In addition, we could accept organs that we currently have to reject because they would not survive even shorter transports without oxygen supply undamaged due to various circumstances.’
The scientists are also hoping for better protection of the donor heart, adds Christoph Knosalla, ‘especially if the removal of the diseased organ from the recipient is particularly time-consuming, for example after mechanical circulatory support or previous opera
The long-term benefits of the HOPE technology will be determined in further studies, and CE certification of the system by the authorities throughout Europe is expected before the end of this year.
‘The recognisable progress is already so great that we hope that we will be able to use this system regularly for long transport times and complex recipient situations for our waiting patients as soon as it is CE-certified,’ concludes Knosalla.
Original publication: Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial (Rega et al., 2024)
Source: press release DHZC (in German only)
