Heart Transplantation From Donation After Circulatory Death Donors

Donation after circulatory death (DCD) has emerged over the last decade as an increasingly used pathway to deceased organ donation. This has led to substantial increase particularly for renal transplants. Although livers, lungs, and pancreata have been used from DCD donors, there has been concern on detrimental effects of warm ischemia on extrarenal organs. The 1 organ that has been left behind almost entirely in this increasingly important area of deceased organ donation is the heart as being most susceptible to ischemic injury. In addition, as implied by the older term “nonheart-beating donation,” it is the arrest of the heart that leads to cessation of the circulation, and until recently, it has not been possible to assess either the severity or the reversibility of the ischemic injury which inevitably affects the heart in the DCD setting. Furthermore, the unfortunate widespread use of the medicolegally incorrect term “donation after cardiac death” has created the false impression even in the minds of many health professionals that the heart “dies” during withdrawal of life support and that this is critical to the determination of death of the donor. How then is it possible to reanimate and transplant a “dead” heart? The medical and legal definition of death after withdrawal of life support is irreversible cessation of the circulation. Jurisdictions vary in the observation time that is legally required before cessation of the circulation can be assessed as being irreversible. Most jurisdictions have legislated an observation time of 5 minutes before death can be declared after cessation of circulation; however, some have determined this to be as short as 2 minutes in line with the original Pittsburgh Protocol1 and more recent international consensus guidelines.2 Under these circumstances, the heart is no different than any other transplantable organ. It has stopped functioning but remains viable for a short period of time after death of the donor. Where it differs from other organs is in its greater susceptibility to the unavoidable warm ischemic injury that occurs during withdrawal of life support and during the interval between circulatory arrest and delivery of myocardial preservation solution. This early clinical experience has demonstrated that distant retrieval and transplantation of hearts from DCD donors is feasible. Several groups including our own have been investigating the possibility of transplanting hearts from DCD donors.3-7 Heart transplantation from DCD donors is not new. The donors for the first human heart transplants performed in the late 1960s belonged to what would currently be defined as Maastrich Category 4 DCD donors.8,9 During this early era, donors and recipients were colocated in the same hospital so that the ischemic insult to the donor heart beyond that which occurred during withdrawal of life support was kept to a minimum. The enactment of brain death legislation effectively brought this practice to an end; however, the reemergence of the controlled (Maastrich Category III) DCD donation pathway for other organs has led to a renewed interest in heart transplantation from these donors. More recently, 3 hearts were procured from DCD donors and successfully transplanted into infant recipients in Denver.10 As with the historical DCD heart transplants, these transplants were performed with donor and recipient colocated in adjacent theatres in the same hospital. Given that most deceased organ donors are multiorgan donors with multiple potential recipients often located across wide geographical distances, it would seem both, unethical and logistically impractical in the current era, to consider moving potential DCD donors to recipient transplant centers. In approaching the challenge of developing a successful clinical heart transplant program from DCD donors, there are 3 critical steps that need to be achieved: first, to develop a strategy which can be administered after death and which enhances the tolerability of the DCD heart to warm ischemic injury; second, to develop a preservation strategy that prevents further injury to the heart during transport between donor and recipient hospitals; and third, to develop a technique that enables the viability of the heart to be assessed before committing the recipient to transplant surgery. Several groups have demonstrated that it is possible to “post-condition’ the DCD heart by modifying the initial flush solution, thereby increasing the heart's tolerance to warm ischemia.4,7 As with other organs, there is active research investigating machine perfusion of the heart using both hypothermic crystalloid solutions and normothermic blood-based perfusion. Both approaches have been shown to be superior to cold storage in preclinical models.5,7,11,12 A clear advantage of normothermic ex vivo perfusion is that it allows the viability of the DCD heart to be assessed before heart transplantation.11 An additional advantage is that there already exists a normothermic ex vivo perfusion device that has been approved for clinical use that has undergone extensive clinical evaluation in the preservation of standard and extended criteria hearts retrieved from donors who have undergone brain death.13 In translating the promising results of preclinical studies into the clinic, it is essential that recovery of hearts from human DCD donors not compromise the recovery of other transplantable organs. This can only be achieved through active collaboration between the local organ donation service, cardiothoracic, and abdominal organ retrieval teams. In our own jurisdiction, revision of existing DCD retrieval guidelines14 and a subsequent public forum involving key stakeholders were instrumental in the development of a protocol for retrieval of the heart together with other organs from the DCD donor. At its current stage, normothermic ex vivo perfusion requires up to 1.5 L of donor blood that need to be drained before the administration of any abdominal organ preservation solutions. We have found in our preclinical studies and in clinical cases to date that this can be achieved within 90 seconds in the absence of antemortem heparin.15 Although the removal of donor blood may briefly delay the administration of preservation solutions for other organs, it does help to decongest the intra-abdominal organs. Several groups have reported successful reanimation of hearts from human DCD donors both in vivo and ex vivo.16-18 In July 2014, Dhital and colleagues performed the first distant retrieval and transplantation of a human DCD heart.15 The transplanted heart demonstrated delayed graft function but within a week, the heart function was normal. Three further DCD heart transplants have since been performed with all recipients making a rapid recovery. The initial 3 cases have been the subject of a report recently published in the Lancet.15 All cases were retrieved from donor hospitals remote from the transplant center with 3 cases requiring air transport. In the first 3 cases, the lungs, liver, and kidneys were also retrieved from the same donor and successfully transplanted, whereas only the heart and kidneys were retrieved from the fourth case. This early clinical experience has demonstrated that distant retrieval and transplantation of hearts from DCD donors is feasible. In our own program, we have currently limited DCD donors to those younger than 40 years with no known history of heart disease and in the absence of major chest trauma. To date, all donors have been young men in their 20s. We expect our acceptance criteria to broaden with increasing experience as has occurred with other organs transplanted from DCD donors. At this point, we have extended warm ischemic times up to 30 minutes. Research in this area will be exciting and understanding mechanisms in more detail may help to push limits here furthermore. Many other questions remain, and these will no doubt be addressed in future studies but for now a threshold has been crossed. Heart transplantation from DCD donors is a clinical reality and has the potential to increase the availability of hearts for transplantation substantially.