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Singh et al. Myocardial protection in cardiac transplantation

concluded that cardiac muscle specific miRNAs could concentrations, free-radical scavengers, antibiotics,
detect early myocardial injury and possibly predict graft and calculated levels of catecholamines and insulin
dysfunction and recovery post-operatively. alongside oxygenated warm blood with a haematocrit
of 20-25%; thus simulating a more “physiological”
NOVEL THERAPIES environment [71] .

The PROTECT trial [72] was a prospective study of 20
The current standard of care for organ preservation of patients who received donor hearts that had been
hearts post explant is cold preservation (usually in an maintained by the OCS in a perfused and physiologic
icebox). Perfusion of the heart with cold preservative beating state for a mean time of 3.7 h. The graft
solution is then followed by explantation and storage of survival rate of 100% at 30 days and the percentage of
the heart at 4 °C. The choice of cardioplegic solution is cardiac related complications was 23%. Additionally,
primarily based on experience of individual centres. The OCS was associated with earlier recovery with a
generally acceptable time for cold preservation is about shorted ventilation time and shorter ICU stay. The
4 h with ISHLT data suggesting that ischaemic times > PROCEED [73] trial was a 20 patient, single arm, non-
6 h associated with primary graft dysfunction [68] . One
of the contributing factors to primary graft dysfunction randomized, Food and Drug Administration approved
may be suboptimal organ preservation alongside the safety and performance study. This study highlighted
role of ischaemia reperfusion injury. the importance of lactate concentration during OCS
use. Hamed’s group concluded that when using the
Goldsmith et al. [69] group analysed the potential benefits OCS for donor heart maintenance, the final serum
of reducing the ischaemic time (IT). They analysed lactate concentrationis the most powerful predictor of
survival rates beyond 20 years’ post-transplantation. The graft failure post heart transplant with high sensitivity
[74]
study showed that median survival post-transplantation and specificity .
was between 10-11 years. Every additional hour of donor
organ IT, conferred a 25% increased risk of death after PROCEED II [75] was the first prospective, open-label,
heart transplantation in the first year after transplant, multicentre, randomised non-inferiority trial comparing
with a 5% increase thereafter (P < 0.001). On average, OCS to current standard of care (cold hypothermic
recipients surviving a decade post-transplantation could static preservation) at ten heart-transplant centres in
potentially gain 0.4 life-years if IT was reduced to 1 h. the USA and Europe. Eligible adult heart-transplant
This worked out to almost 3 life years saved if IT was candidates were randomly assigned (1:1) to receive
reduced to 1 h if someone had IT > 6 h [69] . donor hearts preserved with either the Organ Care
System or standard cold storage. One hundred and
To overcome this limitation, Hassanein et al. [70] thirty patients were recruited and randomised to
proposed the use of a makeshift continuous perfusion Organ Care System group (n = 67) or the standard
device to permit prolonged storage of allografts. cold storage group (n = 63). The 30-day patient and
graft survival rates were 94% (n = 63) in the Organ
At 2 h of reperfusion, the hearts that were continuously Care System group and 97% (n = 61) in the standard of
perfused had higher LV generated pressures and care (P = 0.45). Eight (13%) patients in the Organ Care
lower lactate levels (myocardial acidosis) compared System group and 9 (14%) patients in the standard
to the controls in cold storage. Based on Hassanein’s cold storage group had cardiac-related serious
findings, the Organ Care System (OCS), a continuous adverse events. The results were consistent with non-
perfusion device developed by TransMedics, Inc., inferiority of OCS vs. standard of care in terms of short
Andover, MA, USA, was then used in two phase 1 trials, term outcomes. Donor hearts in the OCS group had
the prospective multi-centre European trial to evaluate a significantly longer preservation (out-of-body) time,
the safety and performance of the Organ Care System but shorter cold ischemia time compared to standard
for heart transplants (PROTECT) trial based in Europe of care. The longest preservation time with the OCS
and the Prospective Multicentre Safety and Effective- was 9 h and 7 min thought to be due to the extra
ness Evaluation of the Organ Care System Device time needed to instrument the donor heart into the
for Heart Use (PROCEED) trial based in the United Organ Care System circuit and optimise the perfusion
States. The OCS consists of a miniature pulsatile characteristics.
pump with an inbuilt inline heater. It is also permits
monitoring of cardiac output, coronary flow and blood Donation following cardiac death however is a new avenue
pressure via the attached monitor. A specific perfusion which resulted in an increase of available organs. Initially
solution consisting of part crystalloid, part glucose and used primarily for kidney transplantation, donor after
amino acids, physiological extracellular electrolyte circulatory death (DCD) was first split into four categories

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 219