Clinical Trial Summary
Heart transplantation is the gold standard treatment for advanced heart failure, with a
survival rate >60% at 10 years. Heart transplantation activity has tended to decline
significantly in France since 2017, with -5% of transplants per year according to the Agence
de la Biomédecine report (La Plaine-Saint-Denis, France, https://rams.agence-biomedecine.fr).
Graft selection criteria have been extended over the past two decades, in particular the
average donor age, which currently exceeds 50 in France. These donors with extended criteria
are more exposed to the risk of acquired coronary lesions. The current indications for donor
coronary angiography are age >55 or >45 with at least two cardiovascular risk factors, but it
is performed in only a third of these cases. Coronary angiography would increase the chances
of graft acceptance by 9%.
At the same time, some heart transplants are rejected for lack of a complete functional
evaluation, or because they present moderate left ventricular dysfunction. In
catecholaminergic stress cardiomyopathy, left ventricular dysfunction is reversible, but its
recovery kinetics are difficult to predict. Ex vivo resuscitation of these grafts on a
perfusion machine could enable functional recovery and acceptance of these grafts for
transplantation. This approach could also be applied to other cardiac grafts harvested from
donors with extended criteria, such as prolonged cardiac arrest.
Graft preservation on ex vivo perfusion machines has enjoyed considerable growth over the
past decade. The Organ Care System (OCS, TransMedics, Andover, USA) is currently the only
transportable perfusion machine available and marketed for clinical use, with experience of
over 1,000 transplants worldwide. OCS technology is based on isolated ex vivo perfusion of
the heart with normothermic blood in Langendorff mode (retrograde aortic perfusion). This
transportable platform enables metabolic evaluation of the graft based on the concentration
of circulating lactate in the perfusate, a criterion of viability and "transplantability".
The aims of this alternative method to static hypothermic preservation of heart grafts are
threefold: 1) to extend the preservation time of the heart graft; 2) to assess graft
viability prior to transplantation; 3) to resuscitate a heart graft harvested after
controlled circulatory arrest (Maastricht 3).
Since February 2019, 31 heart grafts have been placed on OCS in France thanks to the
implementation of an ex vivo perfusion program at the Lille and Rennes teaching hospitals,
and the Marie Lannelongue Hospital. Our preliminary results have recently been accepted for
publication. In this research project, we propose to analyze in real time the quality of
coronary perfusion using vasculoscopy on isolated human hearts placed on OCS, and to put this
anatomical and functional assessment into perspective with the results of heart
transplantation.
Indeed, vasculoscopy is an innovative non-invasive imaging approach that has never before
been applied in the cardiovascular field. We aim to validate this technology in the
assessment of myocardial perfusion quality of the machine-perfused graft awaiting
transplantation, by correlating the signal obtained with perfusion parameters on OCS
(coronary flow, mean aortic pressure, arterial and venous lactate) as well as with transplant
outcomes (primary graft failure rate, recipient survival rate at one month post-transplant).
Myocardial perfusion parameters have never been correlated with heart transplantation
outcomes to date.
