Change of heart
By completing the first non-beating heart transplant in Europe, consultant surgeon Stephen Large could radically reduce the time for those on the donor waiting list. Sarah Holmes discovers the part Freemasons have played in this medical breakthrough
A heart attack in 2008 was the beginning of Huseyin Ulucan’s slow decline into heart failure. By 2014, his condition had deteriorated so severely that he could barely walk. Placed on the transplant list, he joined a long queue of urgent cases. Of the 250 people a year in need of heart transplants in the UK, fewer than half will find a viable organ in time.
While the chance of Ulucan finding a new heart seemed low, everything changed in March 2015 when he was put forward for a bold new transplantation procedure that would reduce the wait for a donor heart from three years to just four months. Traditional transplants only use hearts from donors who have been declared brain-stem dead but still have blood pumping around their bodies. This new procedure used a non-beating heart that had been reanimated in the donor’s body after death.
Using a groundbreaking technique, surgeons kept the heart beating in the donor body for 50 minutes to test its function, before transporting it on a three-hour journey to Papworth Hospital, Cambridgeshire, for transplant into Ulucan. The procedure was the first of its kind to be performed in Europe, and looks set to revolutionise the field by opening up a new supply of donor hearts previously thought unusable.
‘This procedure could increase heart transplantation by 25 per cent in the UK,’ says Stephen Large, the consultant cardiothoracic surgeon (opposite) who oversaw the operation. For three years, he and a research team at Papworth have worked tirelessly to fine-tune the techniques needed to restart and restore a non-beating heart. ‘It means that instead of accepting one in five hearts offered, surgeons will be able to accept two or maybe even three.’
The operation’s success has transformed attitudes towards donation after cardiac death, with Papworth now receiving at least one referral per week. It’s a remarkable feat given the longstanding belief that non-beating hearts become irreparably damaged during the process of death. This breakthrough proves that by re-establishing a fresh supply of blood within 30 minutes of death, the heart can restore its energy supplies enough to start pumping efficiently again.
A £200,000 donation from The Freemasons’ Grand Charity and the Masonic Samaritan Fund allowed Large to establish the project in February 2013, paying for costly organ-care technology as well as the employment of Simon Messer, the cardiothoracic transplant registrar who helped to develop the technique for restarting the heart.
‘It’s difficult to determine whether an organ will function properly once it’s been transplanted. With a heart, it’s even more challenging because it has to be beating,’ says surgeon Charles Akle, a member of the Non-Masonic Grants Committee of The Freemasons’ Grand Charity. ‘The fresher the organ, the better the chance of a successful transplant – there have always been problems with maintaining the quality of a heart, especially one that’s already stopped beating, until it reaches the recipient.’
‘It’s difficult to determine whether an organ will function properly once transplanted. With a heart, it’s even more challenging, because it has to be beating.’ Charles Akle
Keep the rhythm
To this end, the team at Papworth used a revolutionary new technology, the TransMedics Organ Care System, to give the donor heart a steady supply of warm blood. Known as normothermic perfusion, this technique keeps the heart beating as it would inside the body after it’s been removed, so it doesn’t suffer further damage during the journey to the recipient. It’s an essential support system for non-beating hearts, which have already suffered a prolonged lack of blood supply and wouldn’t survive the traditional method of preserving donor organs on ice.
‘TransMedics really takes the heat out of the situation,’ says Large. ‘It allows us to travel greater distances with a “live” heart, and gives us the time to properly assess whether a donor organ is being matched with the right recipient.’
In Ulucan’s operation, the decision to continue with the transplant fell to Steven Tsui, the clinical director of transplantation at Papworth. Watching him mull over his thoughts while the donor heart pumped away on the TransMedics was, Large admits, the most nerve-shredding moment of the procedure.
‘After years of research, that was the final hurdle,’ he recalls. ‘I said to him, “You need to wrestle with your demons here, but this I’m sure is a great heart.” ’ Within minutes, it was being stitched into its recipient and just four weeks later, Ulucan was back at home enjoying his new lease of life. ‘That’s an outstanding recovery by any standard. It must have been a phenomenal heart,’ says Large.
Opening up the donor pool
Without the support of the Freemasons, Large’s research could never have translated into the successful clinical programme it is today. ‘One of the greatest challenges of research is realising the funds to do it,’ says Large. ‘Competition is fierce, and translational programmes like this struggle to attract funding from the Medical Research Council.’
As both a researcher and fund-giver, Charles also understands the challenge. ‘We get pulled in so many different directions at the Grand Charity. It’s impossible to prioritise one research project over another. They are all worthy,’ he says. ‘But we do tend towards applications with a more methodological process, something that’s likely to have a good result that can be developed to benefit other conditions.’
Large’s funding application ticked all the boxes.
‘It provided an immediate and flexible solution for heart transplantation that opened up the donor pool,’ says Charles. ‘It also laid the groundwork for further research into preserving donor organs for as long as possible.’
For Large, the research is only just beginning. ‘Snipping out dodgy organs and stitching in new ones is a replacement therapy. It’s up to the next generation to find out why organs deteriorate and how we can regenerate them organically. I just wish I had another lifetime to see it, because that will be such fun.’
‘A great challenge of research is realising the funds to do it. Competition is fierce, and programmes like this struggle to attract funding from the Medical Research Council.’ Stephen Large
Developed in the US, the TransMedics Organ Care System pumps warm, oxygenated, nutrient-rich blood through a heart, allowing it to keep beating from the moment it’s removed from the donor until it’s implanted in the recipient. A transparent chamber fixed to the top of the machine allows surgeons to watch the attached organ pump blood as it would in a body. Dubbed the ‘heart-in-a-box’, it has also been used to transplant livers and lungs.
Freemasons support novel infection prevention research for patients with liver failure
With more than 50% of patients suffering from liver failure dying prematurely from typically non-life-threatening infections, The Freemasons’ Grand Charity has donated £15,000 to support vital medical research that is aiming to dramatically reduce this terrible statistic.
Dr Antoniades has been appointed by the Medical Research Council (MRC Clinician Scientist Fellowship) to understand why patients with liver failure fail to develop an inadequate immune response to infections that can then lead to fatal sepsis. The aim is to develop novel treatments that will reduce the burden of infection and premature death in patients with liver disease.
Based between Imperial College London and the Liver Intensive Care Unit, King’s College London, Dr Antoniades’s team have already discovered that by inhibiting the activity of a protein found in saliva called SLPI (secretory leukocyte protease inhibitor) in liver failure patients, their natural immune response is able to function as it would in a healthy person.
Dr Antoniades said: 'Our findings indicate that SLPI is a critical mediator of excessive anti-inflammatory responses in liver failure patients which explains their susceptibility to sepsis/infection. Further study of therapeutic options to inhibit the activity of SLPI in the management of sepsis in liver failure is urgently needed.'
The Major Grants Scheme is just one of the initiatives driven by The Freemasons’ Grand Charity which donates around £2.5 million to national charities every year. This particular research project has also been supported by Rosetrees Trust, major funders of life-changing medical research projects.