Maintaining heart function in donors declared 'dead by circulatory
criteria' could improve access to heart transplantation

Date:
March 16, 2023
Source:
University of Cambridge
Summary:
More donated hearts could be suitable for transplantation if they
are kept functioning within the body for a short time following
the death of the donor, new research has concluded.


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FULL STORY ==========================================================================
More donated hearts could be suitable for transplantation if they are
kept functioning within the body for a short time following the death
of the donor, new research has concluded.


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

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

John Louca, a final year medical student at Gonville & Caius College, University of Cambridge, and the study's first author, said: "Heart
transplants are the last bastion for patients with end-stage heart
failure. They are successful -- patients who receive a transplant live
on average a further 13 to 16 years. The biggest problem they face
is actually getting access to a donated heart: many patients will die
before an organ becomes available. That's why we urgently need to find
ways to increase the suitability of donor organs." Though 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 brain death,
or DBD) -- in other words, their brain has stopped functioning entirely.

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 carried out in Cambridge.

DCD is the donation of organs by patients who tragically have a
non-survivable illness. These patients are typically unconscious
in intensive care in hospital and dependent on ventilation. Detailed discussions between doctors, specialist nurses and the patient's family
take place and if the family agree to organ donation, the process starts.

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

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

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

Organ Care Systems are expensive, costing around US$400,000 per
machine plus an additional $75,000 for consumables for each perfused
organ. An alternative, and much more cost-effective approach, is known
as thoraco-abdominal normothermic reperfusion (taNRP). This involves
perfusing the organ in situ in the donor's body and is estimated to cost
around $3,000. Its use was first reported in 2016 by a team at Royal
Papworth Hospital.

In a study published in eClinical Medicine, an international team of
clinical scientists and heart specialists from 15 major transplant
centres worldwide, including the UK, Spain, the USA and Belgium, looked
at clinical outcomes of 157 DCD donor hearts recovered and transplanted
from donors undergoing taNRP.

They compared these with the outcomes from 673 DBD heart transplants,
which represents the 'gold-standard'.

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

Mr Stephen Large, Consultant Cardiothoracic Surgeon at Royal Papworth
Hospital and chief investigator, said: "Withdrawing life support from
a patient is a difficult decision for both the families and medical
staff involved and we have a duty to honour the wishes of the donor as
best we can. At present, one in ten retrieved hearts is turned down,
but restoring function of the heart in situ could help us ensure 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 following taNRP DCD heart transplant, 93% for more
than a year and 84% of patients still alive after five years.

Professor Filip Rega, Head of Clinic at the Department of Cardiac Surgery,
UZ Leuven, Belgium, said: "This promising new approach will allow us
to offer heart transplantation, a last resort treatment, to many more
patients in need of a new heart." The researchers say that some of the benefits from taNRP are likely thanks to the reduced amount of time the
heart was not receiving oxygenated blood, known as its warm ischaemic
time, when compared to direct procurement (that is, when the heart is
removed immediately for transplant, and perfused outside the body). The
median average time was 16.7 minutes, significantly less than the 30
minutes associated with permanent damage to the heart cells.

An added benefit to this approach is that it allows medical teams to simultaneously preserve several organs, such as the liver, pancreas and kidneys, without the need of several organ-specific external machine
perfusion devices. This decreases complexity and costs.

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 uniquely international
effort. 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 rescued."
Dr Beatriz Domi'nguez-Gil, Director General of the National Organisation
of Transplantation in Spain, said: "The results of this collaborative
study bring hope to thousands of patients in need for a heart transplant
every year throughout the world. Its findings reveal that DCD heart transplantation based on taNRP can lead to results at least similar to
the gold standard and increase hearts available for transplantation in
a manner that contributes to the sustainability of health-care systems."
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========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
text of this story is licensed under a Creative_Commons_License. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. John Louca, Marco O"chsner, Ashish Shah, Jordan Hoffman, Francisco
Gonza'lez Vilchez, Iris Garrido, Mario Royo-Villanova, Beatriz
Domi'nguez-Gil, Deane Smith, Leslie James, Nader Moazami, Filip
Rega, Janne Brouckaert, Johan Van Cleemput, Katrien Vandendriessche,
Vincent Tchana-Sato, Diawara Bandiougou, Marian Urban, Alex Manara,
Marius Berman, Simon Messer, Stephen Large, Nirav Patel, Rohan
Sanghera, Constantinos Kapetanos, Antonio Rubino, Sai Bhagra,
Luis-Alberto Martinez-Marin, Jordan Allen, Chindu John, Daniel
Normington, Steven Tsui, Aravinda Page, Vanessa Chow, William
McMaster, Alicia Pe'rez- Blanco, Elisabeth Torres, Jose' Cuenca,
Fernando Mosteiro, Marta Farrero, Elena Sandoval, Manuela Camino,
Juan Ja'urena, Fabrizio Sbraga, Eva Oliver, Antonio Quintana,
Vincente Morant, Belen Este'banez, A'lvaro Rocafort, Manuel Cobo,
Francisco Nistal, Manuel Go'mez-Bueno, Marina Pe'rez-Redondo, Arne
Neyrinck, Diethard Monbaliu, Laurens Ceulemans. The international
experience of in-situ recovery of the DCD heart: a multicentre
retrospective observational study. eClinicalMedicine, 2023; 58:
101887 DOI: 10.1016/j.eclinm.2023.101887 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230316140928.htm

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