Abstract
Background: Heart transplant from controlled donation after
circulatory death (cDCD) is an emerging strategy that is rapidly
expanding and may help increase the heart donor pool.
Materials and Methods: The use of thoracoabdominal normothermic
regional perfusion (TANRP) with extracorporeal membrane oxygenation
device has allowed to perform cardiac transplantation after cDCD.
Several experiences have been carried out in recent years, however the
maximum cold ischemia time is still unknown. We present a successful
case of heart transplantation using a graft from cDCD from another
hospital with 201 minutes of cold ischemia time, the longest published
in Europe.
Discussion and conclusion: Heart transplant from cDCD could be
a good alternative to brain dead donation. This experience suggests than
nonlocal cardiac donation in controlled asystole could tolerate long
periods of cold ischemia time and break the main barriers in cardiac
donation after circulatory death.
INTRODUCTION
The shortage of donors and the long waiting list for heart
transplantation (HT), have led to search alternatives to brain-dead
donation, reviving interest in controlled donation after circulatory
death (cDCD) programs (1). It is developed using thoracoabdominal
normothermic regional perfusion (TANRP) with extracorporeal membrane
oxygenation (ECMO) devices and preserved in cold storage, allowing to
perform cardiac transplantation without ex-situ perfusion. Most of the
cases reports with this technique were published of donor and recipient
in the same hospital or at a very short distance (2).
Due to the peculiarities of the HT in Canary Islands, Spain, we were
obliged to try to expand our radius of action by accepting donors of the
entire island territory. We present a cDCD cardiac transplant
successfully performed in Gran Canaria, with a donor from La Palma, an
island located 70 minutes away by helicopter (250 kilometres). This
determined a cold ischemia time of 201 minutes, the longest published in
Europe to date with the TA-NRP technique and cold storage.
Case report
A 47-year-old male, with no personal history, admitted to the intensive
care unit (ICU) after severe head injury secondary to a fall from
height. After 33 days, with irreversible catastrophic brain damage, the
responsible medical team in consensus with the family decided to
withdraw life – sustaining therapies (WLST). Evaluated by analytical
studies, electrocardiogram and echocardiography, he was accepted for
cDCD cardiac transplant after obtaining family consent. The usual heart
transplant team went to La Palma hospital, equipped with a portable ECMO
device and all the necessary material to carry out the extraction.
The cDCD process was carried out according to the protocol of our center
approved by the National Transplant Organization, using TANRP with ECMO
devices and cold storage preservation.
The functional warm ischemia time (WIT) defined as the time between
systolic blood pressure < 60 mmHg and the start TANRP was 11
minutes. The PRN–TA time was 15 minutes (see figure 1).
The recipient was a 56-year-old man with advanced heart failure due to
ischemic cardiomyopathy, included 38 days HT waiting list. He was
informed of the peculiarities of the HT, signing a specific informed
consent for HT with cDCD. An orthotopic HT with bicaval technique was
performed. The cold ischemia time was 201 minutes. He was transferred to
the ICU, requiring norepinephrine 0.6 mcg/kg/min, isoprenaline 0.2
mcg/kg/min, and milrinone 0.4 mcg/kg/min which were gradually withdrawn.
He was extubated 30 hours after HT and was discharged to the ward six
days later, where he remained fifteen days more (see table 1). The
transthoracic echocardiogram showed good biventricular function (left
ventricular ejection fraction 67%), without significant valve disease.
After two months of follow-up, the patient is asymptomatic. Two
endomyocardial biopsies were performed with a mild cellular rejection
(grade 1R of the ISHLT 2004), while the coronary angiography done a
month later, showed a slight lesion in the proximal anterior descending
artery.
DISCUSSION
HT from cDCD is estimated to increase exponentially in the following
years, accounting more than 10% HT per year (2). Published data with
cardiac donors in cDCD showed similar short-term results compared with
brain-dead donors, however more studies to assess the long-term impact
are required (3).
After the reinitiation of HT activity from donors in controlled
asystole, different extraction protocols have been used with different
donor acceptance criteria. Most of the Spanish protocols for HT in cDCD
include donors under 55 years old, although the first cases were
restrictive in the inclusion criteria (< 45 years) (4) (5). An
exhaustive cardiac evaluation (including electrocardiogram,
echocardiogram, biomarkers and sometimes coronary angiography) and the
re-evaluation after cessation of circulatory function and the beginning
of TANPR with ECMO device, could allow, as in our case, to expand the
inclusion of donors older than 45 years and probably in the future, also
order than 55 years.
Because it is a recent technique in most of the protocols, it is
recommended that extraction and transplant are performed in the same
hospital, since the maximum cold ischemia time that these hearts can
tolerate is unknown, without increasing the risk graft dysfunction or
morbimortality transplant associated. Although preclinical studies
demonstrated adequate tolerance to ischemia times of less than two hours
(6) (7), the Tennessee group (8) confirms the safety of 225
minutes. However, in this cohort, recipients were younger and, in some
cases, used different cDCD heart transplant protocols (shorter “no
touch” time), compared to our case.
CONCLUSION
In Spain, the longest cold ischemia time published cDCD heart transplant
in adult was 80 minutes. Our case was a cDCD performed in a hospital
located on another island of the Canary Island, which determined the
longest cold ischemia time. This experience suggests that nonlocal
cardiac donation in controlled asystole in adults with PRNTA could
tolerate long periods of cold ischemia, without compromising the
prognosis, at least in the short term.