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Page 10 of 17 Singh et al. Vessel Plus 2018;2:33 I http://dx.doi.org/10.20517/2574-1209.2018.28

Table 1. Different types of cytolytic induction therapy available (adapted with permission from Wahlers [92] )
Substance Origin Dosages applied Routes investigated Monoclonal/polyclonal
Antilymphocyte-Globulin ATGAM Horse Various 7-14 days IM Polyclonal
Antithymocyte-Globulin Bieber-ATG Tecelac Rabbit 1, 5-3 mg/kg per day IM/IV Polyclonal
1-10 days
OKT III antibody Mouse 5-10 mg/day IV Monoclonal
4-14 days
BMA 031 antibody Mouse Experimental IV Monoclonal
Anti-LFA antibody Synthetic Experimental IV Monoclonal

negative impact of high nephrotoxic ciclosporinCiclosporin/tacrolimus levels. It effectively allows bridg-
ing of immunosuppression until a steady state is reached for the regular immunosuppression medications.
Most centres use a combination of the abovementioned immunosuppressants to achieve adequate im-
munosuppression. In 2006, Kobashigawa led a trial comparing 3 different immunosuppression regimes,
[95]
micro-emulsion Ciclosporin with MMF, tacrolimus with MMF or tacrolimus with sirolimus .

The 343 heart transplant recipients in this trial were randomized to receive corticosteroids and on of the
mentioned regimes. Cytolytic induction therapy was used for up to 5 days. The primary endpoint of moder-
ate rejection or haemodynamic compromise rejection requiring treatment showed no significant difference
between the three groups at 6 months and 1 year. The probability of treated rejection was significantly lower
in both the tacrolimus groups compared with the micro-emulsion Ciclosporin/mycophenolate mofetil group.
The tacrolimus/sirolimus group had more fungal infections and more impaired wound healing.

On the other hand, recent trials involving combinations with everolimus have shown promising results
[96]
[97]
including reduced cytomegalovirus infections , reduced cutaneous cancer incidence , and CAV attenua-
[98]
tion effects .
CURRENT STATUS OF HEART TRANSPLANTATION
Heart transplantation is considered to be the “gold-standard treatment” for refractory advanced heart
failure in carefully selected patients [99-101] . A major limiting factor of transplantation is the emerging gap
between the number of donors (available grafts) and the number of patients on the waiting list. This issue
[102]
is apparent even in the neighbouring France . The utilization of marginal donors or expanded-criteria
donors has steadily increased over the decades. Part of the decision-making process currently between
physician, surgeon and patient includes discussing the potential options available. Currently, the choices
include continued medical therapy (5% to 10% weekly mortality risk), mechanical circulatory support (10%
to 15% operative risk), or a transplant which may or may not include a clause for marginal organs.

[103]
The “Standard Donor” or “Traditional Criteria” for a donor as suggested by Copeland is as follows: (1)
age < 50 years; (2) echocardiogram showing no important segmental abnormalities or global hypokinesis,
ejection fraction greater than 50%, and normal valves; (3) inotropes less than 15 µg/kg/min of dopamine;
(4) donor to recipient weight ratio 1.5 to 0.7; (5) cold ischemic time less than 4 h; (6) no donor infection; (7)
negative serology for hepatitis B, hepatitis C, and human immunodeficiency Virus; and (8) normal electro-
cardiogram or minor ST-T wave abnormalities, with no conduction system disease.

The rising number of patients listed for heart transplantation has resulted in an increased number of do-
nors from beyond the “standard criteria” pool as a result of the undersupply of available organs. “Marginal
Donors” as they are termed would, under conventional transplant guidelines, be declined as potential or-
[104]
gan donors . Median waiting times in the UK for hearts on the non-urgent list is currently 1280 days and
[105]
26 days for the urgently listed [Figure 1].