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• W4313339860 abstract "Of all organs retrieved for transplantation from deceased donors, the heart is the most susceptible to ischemic injury. Moreover, this susceptibility increases with increasing donor age.1 As a consequence, many heart transplant programs place an upper limit on donor age of 60 y or even less. For these reasons, hearts are retrieved from a minority of deceased donors.2 Although the advent of heart transplantation from donation after circulatory death (DCD) donors offers hope of expanding the donor pool,3 the large majority of donors’ hearts are retrieved from heart-beating donation after brain death (DBD) donors. In the latter scenario, hearts are arrested by the administration of 1 L of cold preservation solution. Following retrieval, the heart is placed in a bag containing 1 L of cold crystalloid solution. This bag is then placed in a second bag also containing 1 L of cold solution and then packed in a portable ice box for transport from the donor to recipient hospital.4 This technique has provided reasonably reliable donor heart preservation for periods up to 3 h; however, as the ischemic time increases further, there is a progressive increase in the risk of severe early graft dysfunction and associated mortality.5 Historically, donor heart preservation research largely focused on modifications to the cardioplegia and storage solution with the aims of minimizing ischemic injury, preventing the development of myocardial edema during storage, and preventing reperfusion injury following implantation. Currently, all donor heart preservation solutions rely on profound hypothermia to slow myocardial metabolism. Although myocardial metabolism is slowed‚ it is not arrested. In the absence of oxygen delivery, myocardial viability is maintained via anaerobic metabolism‚ which rapidly depletes high energy stores and results in progressive lactic acidosis. This in turn activates the sodium hydrogen exchanger, resulting in intracellular sodium and then calcium overload. More recently, it has been found that lactic acidosis also activates necroptosis via an acid-sensing ion channel (ASIC1a) in the cardiomyocyte membrane.6 Placing the donor heart in a bag of cold solution and then in a portable ice box is simple but not without its problems. Direct contact of the myocardium with ice can produce freezing injuries with myocyte necrosis and early graft dysfunction. Conversely, poor insulation may allow excessive temperature rise during transport and subject the heart to warm ischemic injury. In this edition of the journal, Zhu and colleagues from Stanford University report their experience with the Paragonix SherpaPak temperature-controlled hypothermic storage system for donor heart preservation and transport.7 Its main stated advantage over traditional static cold storage (SCS) is more precise temperature control during transport with the heart maintained between 4.5° and 6.5° centigrade. The authors switched from SCS to using the SherpaPak system (Paragonix Technologies, Cambridge, MA) in June 2020. They compared the outcomes of the first 62 heart transplant recipients with a historical cohort. Overall, recipients of hearts transported with the SherpaPak device were older‚ and the mean total allograft ischemic time was significantly longer in the SherpaPak group at just over 4 h. Despite these unfavorable baseline characteristics, postoperative requirement for perioperative transfusion of blood products was lower in the SherpaPak group‚ and major clinical outcomes‚ including primary graft dysfunction, hospital length of stay‚ and survival‚ were similar between groups. Although the findings appear promising‚ there are several limitations. Firstly‚ this is a single-center retrospective analysis with small numbers. Furthermore, as acknowledged by the authors, their findings are confounded by the fact that the surgical team modified their surgical implant technique after the introduction of the SherpaPak system (although unrelated to the use of SherpaPak), resulting in a significantly shorter warm ischemic time for donor hearts retrieved with the SherpaPak system. The manufacturer has established an observational postmarket registry (called the Guardian Heart Study, NCT04141605) to monitor the clinical outcomes of heart transplant recipients whose hearts have been retrieved using the SherpaPak system. According to the manufacturer’s website, >1700 heart transplants have been performed using the SherpaPak system across 60 Heart Transplant Units in the United States and Europe. An abstract of the first 383 US patients included in the registry reported lower rates of severe primary graft dysfunction and a trend of improved survival for recipients of hearts retrieved with SherpaPak compared with SCS.8 Unfortunately, the registry shares many of the limitations of the study by Zhu and co-authors. As Zhu and co-authors conclude in their study, an adequately powered randomized multicenter randomized trial is warranted to establish whether the SherpaPak system provides superior donor heart preservation compared with SCS. Given the rapid uptake of SherpaPak, by multiple Transplant Units, such a trial appears quite feasible and would provide more compelling evidence than an observational registry. SherpaPak is recommended for the storage of standard criteria donor hearts for up to 4 h. There are still many donor hearts that are not covered by these recommendations‚ including DCD hearts, hearts from older DBD donors, donor hearts requiring high levels of inotropic support, and those demonstrating impaired global or regional left ventricular function. A study of the use of SherpaPAk in the transport of DCD hearts that have been resuscitated in situ using thoracoabdominal normothermic regional perfusion has been registered on the clinical.gov website (NCT05038943)‚ but no results have as of yet been reported. The other major innovation in donor heart preservation has been in machine perfusion‚ whereby an oxygenated solution is perfused through the heart at either hypothermic or normothermic temperature.9 Normothermic machine perfusion has enabled direct procurement and resuscitation of hearts from DCD donors and may also enable successful transplantation of marginal hearts from brain-dead donors. Initial experience with hypothermic machine perfusion also shows promise‚ suggesting improved preservation of hearts from DBD donors.10 Both technologies are considerably more expensive than SherpaPak, which in turn is substantially more expensive than SCS. Nonetheless, if these innovations in donor heart preservation improve the quality of donors’ hearts and expand the donor pool, thereby making heart transplantation safer and more available to patients with end-stage heart failure, then the expense will be worth it." @default.
• W4313339860 created "2023-01-06" @default.
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• W4313339860 date "2022-12-13" @default.
• W4313339860 modified "2023-10-18" @default.
• W4313339860 title "Cutting the Ice in Donor Heart Preservation" @default.
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