**8. Post-operative ECMO use in heart transplantation**

Indications for the use of ECMO mechanical circulatory support following a heart transplant include the occurrence of hyperacute graft rejection, post-operative bleeding, severe vasoplegia, and primary graft dysfunction.

Hyperacute rejection occurs within minutes to hours following a heart transplant, results from an antibody-mediated rejection (AMR) in response to HLA donor specific antibodies, and results in rapid damage to the graft with deposition of C4d complement. The diagnosis of antibody mediated rejection was previously, made in cases of graft dysfunction in the absence of cellular rejection. Recently, the requirement of histological evidence of antibody mediated injury was included [52, 53]. This inclusion helps to differentiate hyperacute rejection from non-immunological causes (NIC) of graft dysfunction. Notably, transplant guidelines recognize that AMR may occur when neither donor specific antibodies nor C4d deposition is present. Both AMR and NIC may present with severe pulmonary edema, profound coagulopathy, and biventricular failure. With current practice of HLA matching, hyper-acute rejection due to AMR has become rare [54, 55]. There are still instances of hyperacute graft dysfunction in orthotopic heart transplantation in the presence of non-HLA antibodies. These have been attributed to anti-angiotensin type I receptor antibodies [56].

The entities of vasoplegia and PGD after orthotopic heart transplantation have significant overlap with both conditions having a common factor of severely reduced afterload. It is possible that either entity may be complicated by the other for example, the increased capacity of the vascular system resulting from loss of vascular tone and attendant vasodilation as seen in vasoplegia may, in the presence of a denervated heart and loss of cardioaccelerator response, lead to ineffective cardiac output and resulting fall in afterload. The resulting cardiovascular collapse leads to failure of coronary perfusion and other end-organs. PGD which may result from myocardial stunning, leading to inadequate cardiac output which is beyond the capacity of the initial vasoconstrictive response to maintain cardiac afterload. The report of increase in PGD with longer ischemic time supports the second theory [57, 58]. A third possibility is autonomic dyssynergia between the denervated cardioaccelerator beta 1 supply to the heart and the vasoconstrictive alpha supply to the vascular system.

Regardless of the pathogenesis, the use of a VA-ECMO in patients with severe primary graft dysfunction and/or vasoplegia following heart transplantation is recommended in situations of escalating inotropes and poor ventricular function [59–61]. VA-ECMO empties the right heart, allows systemic circulatory support and increases afterload makes this modality an appropriate technology for the management of PGD and vasoplegia. Pressure dynamics following institution of VA ECMO may result in failure of the passive aortic valve to open due to the continuous pressurization of the aorta above the left ventricular pressure. This could result in LV stasis and thrombosis [62]. Failure of left ventricular emptying may result in distension and increased wall tension, decrease of subendocardial perfusion and perpetuate the graft failure [63]. The target should be to prevent rather than treat ECMO related complications in the post-transplant period.
