Preservation of heart function in donors declared ‘circulatory dead’ could improve access to heart transplantation — ScienceDaily

More donated hearts could be suitable for transplant if they are kept functioning inside the body for a short time after the donor’s death, new research has found.

The organs are kept working by restarting local circulation to the heart, lungs and abdominal organs — but, crucially, not the brain — of patients whose hearts have stopped beating for five minutes or more and have been pronounced dead with circulatory criteria (donation after circulatory death or DCD).

It is hoped that this technique could increase the number of usable donated hearts by up to 30% in the future, helping to address the shortage of transplant organs. In 2021, 8,409 heart transplants were reported to the Global Observatory of Donations and Transplants (GODT) from 54 countries. This activity contrasts with the 21,935 patients on the heart waiting list in 2021, of whom 1,511 died while waiting and many others became too ill to receive a transplant.

John Louca, a final year medical student at Gonville & Caius College, University of Cambridge, and first author of the study, said: “Heart transplants are the last line of defense for patients with end-stage heart failure. They are successful — patients who receive a transplant lives on average another 13 to 16 years. The biggest problem they face is actually gaining access to a donor heart: many patients will die before an organ becomes available. So we urgently need to find ways to increase suitability of the donor’s organs”.

Although the first heart transplant performed at the Groote Schuur Hospital in Cape Town (South Africa) in 1967 was obtained from a DCD donor, this technique was abandoned and replaced by heart transplants obtained from donors confirmed dead using neurological criteria (donation after stroke death, or DBD) — in other words, their brain has stopped working completely.

Until recently, heart transplants worldwide were still performed only with organs obtained from DBD donors. However, in recent years, heart transplants from DCD donors have become a clinical reality worldwide thanks to years of research conducted in Cambridge.

DCD is the donation of organs from patients who tragically have a disease that cannot be survived. These patients are usually unconscious in the hospital intensive care unit and are ventilation dependent. Detailed discussions are held between doctors, specialist nurses and the patient’s family, and if the family agrees to organ donation, the process begins.

After the treatment is withdrawn, the heart stops beating and begins to sustain tissue damage. After 30 minutes, it is believed that this damage becomes irreversible and the heart is useless. To prevent this damage, at the time of death these non-beating hearts are transferred to a portable machine known as an Organ Care System (OCS), where the organ is perfused with oxygenated blood and evaluated to see if it is suitable for transplantation.

This technique was pioneered by Royal Papworth Hospital NHS Foundation Trust in Cambridge, whose transplant team performed the first DCD heart transplant in Europe in 2015. Royal Papworth has since become the largest and most experienced DCD heart transplant center in the world.

DCD heart transplantation started simultaneously in Australia, followed by Belgium, the Netherlands, Spain and the USA. According to GODT, 295 DCD heart transplants were performed in these six countries in 2021.

Organ care systems are expensive, costing approximately US$400,000 per machine plus an additional US$75,000 for consumables for each organ perfused. An alternative, and much more cost-effective approach, is known as thoracoabdominal normothermic reperfusion (taNRP). This includes injecting the organ on the spot into the donor’s body and is estimated to cost around $3,000. Its use was first reported in 2016 by a team at the Royal Papworth Hospital.

In a study published in Electronic Clinical Medicine, an international team of clinical scientists and cardiac specialists from 15 major transplant centers worldwide, including the UK, Spain, USA and Belgium, reviewed the clinical outcomes of 157 DCD donor hearts retrieved and transplanted from donors who underwent taNRP. They compared these with results from 673 DBD heart transplants, which represents the ‘gold standard’.

The team found that overall, the use of taNRP significantly increased the donor pool, increasing the number of heart transplants performed by 23%.

Mr Stephen Large, Consultant Cardiothoracic Surgeon at Royal Papworth Hospital and lead researcher, said: “Withdrawing life support from a patient is a difficult decision for both the families and the medical staff involved and we have a duty to honor the wishes of the donor as best we can. Currently, one in ten recovered hearts is rejected, but restoring heart function in situ could help us ensure that more donor hearts find a recipient.”

Survival rates were comparable between DCD and DBD heart transplantation, with 97% of patients surviving for more than 30 days after taNRP DCD heart transplantation, 93% for more than one year, and 84% of patients still alive after five years.

Professor Filip Rega, Head of Clinic at the Department of Cardiac Surgery at UZ Leuven, Belgium, said: “This promising new approach will allow us to offer heart transplantation, a treatment of last resort, to many more patients in need of a new heart. “

The researchers say some of the benefits from taNRP are likely due to the reduced time the heart is deprived of oxygenated blood, known as warm ischemic time, compared to immediate supply (that is, when the heart is immediately removed for transplantation and infused out from the body). The median mean time was 16.7 minutes, significantly shorter than the 30 minutes associated with permanent heart cell damage.

An added advantage of this approach is that it allows medical teams to simultaneously preserve multiple organs, such as the liver, pancreas and kidneys, without the need for multiple external organ-specific perfusion machines. This reduces complexity and cost.

Professor Ashish Shah, Head of the Department of Cardiac Surgery at Vanderbilt University Hospitals, Nashville, USA, said: “Heart transplantation has been and always will be a unique international endeavour. The current study is another example of effective international collaboration and opens a new frontier, not just in transplantation, but in our basic understanding of how all hearts can be saved.”

Dr Beatriz Domínguez-Gil, Director General of the National Transplantation Agency in Spain, said: “The results of this collaborative study bring hope to the thousands of patients who need a heart transplant every year around the world. Its findings reveal that the DCD heart is the taNRP-based transplantation may lead to outcomes at least similar to the gold standard and increase available hearts for transplantation in a way that contributes to the sustainability of health care systems.”

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