Программа трансплантации сердца в эпоху механической поддержки кровообращения: опыт Республики Казахстан
C 2012 по 2016 г. выполнено 42 пересадки сердца. Выживаемость к 12 мес составила 80%.
С учетом особенностей Казахстана разработана программа дистанционной доставки и консервации сердца с помощью системы сохранения органов (OCS-Transmedics - Organ Care System).
В статье дано сравнение этой методики с холодовой консервацией донорского сердца.
5-летний опыт авторы расценивают как довольно успешный.
Ключевые слова:дистанционная пересадка, механическая поддержка кровообращения сердца, консервация сердца
Клин. и эксперимент. хир. Журн. им. акад. Б.В. Петровского. 2017. № 3. С. 49-53.
Статья поступила в редакцию: 25.05.2017. Принята в печать: 15.06.2017.
Technical advances in the field of left ventricular
assist devices (VAD) offer solutions that are not
only about survival but also about improving the quality of patients’ life in time of donor scarcity
. Possibly, VADs can replace heart transplantation
(HTx) in the future, especially with the advancement
of new technologies in the field of medicine . But
today, HTx is the treatment of choice for patients with
end-stage heart failure [3-5].
The first open-heart surgery in Kazakhstan was
performed in 1958. Prior to 2011, there were no
mechanical circulatory support and HTx programs.
Patients with severe heart failure could only receive medical treatment. In 2011 new National Research Cardiac Surgery Center (NRCSC) in Astana,
Kazakhstan, was first in the country to establish
mechanical circulatory support program. The Center
provides VAD support to all regions of our country.
From November 2011 to April 2017, 226 patients
underwent implantation of 232 VADs at NRCCS. In
2012 we initiated heart transplantation program in
Kazakhstan. Between 2012 and 2017, 51 patients
with heart failure underwent heart transplantation,
and we used the TransMedics (Transmedics, Inc., Andover, MA, USA) Organ Care System (OCS) for donor
heart preservation in 43 cases. So, before performing
the first HTx we implanted approximately 50 VADs
Kazakhstan is the 9th largest country in the world,
for donor hearts to be transplanted from distant regions to our Center they often need to be transported
up to 2000 km . There are currently two methods
for ex vivo preservation of donor hearts: standard cold
storage and a system for ex vivo heart perfusion. The TransMedics OCS is a portable ex vivo organ perfusion
and monitoring system that was designed to preserve donor hearts in near-physiologic functioning
state . This method decreases the risk of time-dependent ischemic injury that usually takes place during standard cold storage. At some institutions usage
of the OCS is now standard of care . This report describes the initial experience and clinical results of the
first five years of the HTx program in Kazakhstan.
In this study we performed a prospective descriptive analysis of 42 patients underwent heart
transplantation from 2012 to 2016. We used OCS in
34 (81%) cases.
All the data were collected at NRCSC. Perfusion
and cardiac function parameters were continuously
monitored and the donor heart was perfused in the
The primary outcome was cumulative survival.
Secondary outcomes evaluated included freedom
from graft failure and incidence of adverse events.
We also collected data on perioperative parameters
including OCS perfusion measures. Post-operative parameters of interest were time in intensive care unit
(ICU), extracorporeal membrane oxygenation (ECMO)
duration (if used) and Tissue Doppler Imaging (TDI)
on days 3, 7. Eligible recipients were on the waiting
list for HTx at our center. All patients provided written informed consent to be involved in the study and
to allow their data to be used for this analysis. We
defined total preservation time as the heart perfusion
time while in the OCS. Total ischemic time was defined as time from donor heart explantation to recipient implantation.
In the OCS “Transmedics” (Fig. 2), oxygenated
blood is pumped into the aorta, perfusing the coronary arteries . The coronary sinus flow then passes
through the tricuspid valve (as both the superior and
inferior vena cava are sutured closed) and is ejected
by the right ventricle into a pulmonary artery cathe
ter, and returned to the blood reservoir. After the donor has been heparinized, a portion of the normo-thermic blood (500-750 ml) is retrogradely collected
for blood cardioplegia. The donor blood (1200-
1500 ml) is collected prior to antegrade cardioplegia
and aortic cross-clamping and is used to prime the
perfusion module. A portion of the normothermic
blood (500-750 ml) is used for short-acting cardioplegia. The aorta and pulmonary artery of the donor heart are cannulated and the heart is connected
to the OCS device. Then, the heart is reanimated to
normal sinus rhythm. Pulsatile flow is generated
by a diaphragmatic pump, and an integrated plate
heater maintains normothermia . The pump flow
and solution flow rates of the OCS are adjusted to
maintain the mean aortic pressure between 60 and
90 mm Hg, and coronary blood flow between 650 and
850 ml/min. Throughout the perfusion process with
the OCS, arterial and venous lactate samples are taken
every 30 min from the system perfusate to assess the
adequacy of perfusion. The samples are analysed with
a handheld lactate analyser (i-Stat, Abbott Diagnostics, East Windsor, NJ, USA). Upon arrival at our Center, the donor heart is arrested with approximately
one liter of blood cardioplegia and is disconnected
from the OCS for implantation into the recipient.
Transplantation and preoperative care proceeded according to the standard procedures of our Center.
Descriptive analysis was performed by presenting
the mean±SD for continuous data. Outcome measures
used were all-cause mortality using Kaplan-Meier
survival curves. Statistical analyses were performed
using SPSS Statistics version 22.
The recipient and donor characteristics are
shown in Tables 1, 2. There were 8 instances where
recipients had a different blood type than their
donors. The median (range) age of patients with a transplanted heart is 40±14 (17-63) years. 71.4%
(n=30) of recipients were males. 42.82% of transplanted patients had left VAD implantation prior to
the HTx, and 2 (4.76%) of them had right VAD implantation. The average waiting time of transplantation was 275±443 days (2-1610). All patients
received immunosuppressive therapy consisting of
induction therapy - anti-thymocyte immunoglobulin and the basic therapy: calcineurin inhibitors, mycophenolic acid preparations and glucocorticoids.
Mean ex vivo perfusion time in the OCS was
266.5±86.7 min. The longest preservation time
in the OCS was 7.5 hours. Mean total preservation
time was significantly longer in the OCS group than
in the standard cold storage group (Fig. 3). However, mean total ischemia time was significantly
shorter in the OCS group than in the standard cold
storage group. Mean venous lactate at the start of
perfusion was 2.8±0.7 mmol/l. At the end of perfusion, the mean venous lactate was 7.1±1.1 mmol/l.
All the donor hearts had stable perfusion and metabolic characteristics in the OCS (Fig. 4). Three,
seven days TDI results were normal in all recipients
(Table 3). Mean ICU stay was 15±22 days (range:
2-122). Mean time on ECMO for the 23 (54.76%)
patients were 3.6±2.4 days. Mean length of stay at
Center after operation was 29.7±12.5 days.
Kaplan-Meier survival estimates for all patients
after HTx were 90% after 3 months, 82% after six
months and 80% after twelve months (Fig. 5). Survival rate of patients in OCS group was slightly different from standard cold storage group recipients’
survival (Fig. 6). In total, 8 patients (7 cases from
OCS group, 1 - standard group) died (19%): before
30 days - 1 patient, 60 days - 2 patients, and more
than 60 days - 5 patients.
In the early postoperative period after HTx
11 (26.1%) patients had the following complications: 13 (30%) - resternotomy due to bleeding,
3 (7%) - sepsis, 1 (2.3%) - stroke, 2 (4.7%) - lymphorrhea from groin area, 2 (4.7%) - heart rhythm
disturbances, and 6 patients (14.3%) had pneumonia. There was no graft rejection.
Kazakhstan is a large country with low population
density (6.4 persons/km2). Prior to 2011 year there
were no VAD and HTx programs in our country. The
reasons of undeveloped HTx program were donor deficit, huge territory, and mentality of people. In 2011
the NRCSC launched the surgical heart failure treatment program in Kazakhstan with starting of the VAD
implantation. VAD program was the trigger to development of HTx program in our country.
Currently, we are the sole HTx center in a large
country and therefore, donor hearts often need to be transported over long distances (more than
2000 km). Despite the prolonged mean preservation time, the patients from OCS group had a shorter
mean ischemia time than the standard cold storage
group. The OCS prolongs out of body time to at least
8 hours, expanding possibilities for organ procurement from distant sites. In Australia, a donor heart
was successfully transplanted after 10.5 h on the
OCS . We initiated this study to investigate a
new method of heart preservation in this context.
Also, the using of ex vivo perfusion system is good
option for redo recipients, when additional time is
needed to perform cardiolysis. The ability of the OCS
to reanimate hearts from donors after cardiac death
might present a new pool of donor hearts for transplantation .
In our small cohort, survival and incidence of adverse events were acceptable compared with the experience of other centers [10-11], and demonstrate
the feasibility of the OCS. Other outcomes such as OCS
perfusion measures, lactate trends and length of ICU
stay were all within the expected range for our Center.
Hamed et al.  defined a cut-off value of ending lactate 4.9 mmol/l as the most powerful predictor
of graft failure after HTx. In our study we use donor
hearts with the venous lactate at the end of perfusion more than 5 mmol/l, due to the severe shortage
of donor organs. We commonly use ECMO after HTx,
during the postoperative recovery period to reduce
the adverse effects of roller cardiopulmonary bypass.
In conclusion, our analysis has several limitations
including lack of randomization and a small cohort
of patients. Children are not eligible to be heart donors in Kazakhstan under current laws, therefore, we
rarely perform HTx in children because of the low possibility of appropriate adult donor hearts becoming
available. Our observations, while preliminary, show
that OCS could be a safe method for myocardial protection in distant procurement and preservation of
donor hearts. Further research in this direction will
be helpful to understand outcomes in different clinical subgroups.
Source of Funding: This work was supported by
the Government of Kazakhstan.
Declaration of interest: none declared.
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