Improving donor heart preservation

The accompanying paper by Cannata et al. [1] identifies the important challenges for the continuing efforts of cardiac surgeons to improve donor heart preservation. To expand the benefits and spurred by remarkable successes, transplantation has been offered to older and sicker patients and, to increase the donor pool, older hearts have been accepted. As indicated by the accompanying paper, the current methods of donor heart protection and transport have produced impressive results. However, cold storage can delay the recovery of ventricular function, induce at least transient endothelial injury [2] and predispose to late transplant vasculopathy. Therefore, cardiac surgeons have an urgent need to improve donor heart preservation. The success of heart transplantation has encouraged the acceptance of older heart failure patients into transplant programmes. To expand the pool of donor organs, surgeons have increasingly employed older donor organs with good results, as reviewed in this paper. However, a recent report from Milan, by Bruschi et al., [3] demonstrated that the expanded use of older donor hearts was associated with an increased risk of acute graft failure and hospital mortality. In the current report by Cannata et al. [1], they extended those observations and found that the combination of older donors and older recipients was an independent predictor for in-hospital mortality. Both older donors and older recipients have an increased susceptibility to ischaemic injury with delayed recovery of ventricular function. Previous studies have demonstrated that older hearts sustained greater ischaemic injury during cardioplegic arrest [4]. Older recipients have dysfunctional stem cells and a diminished regenerative stem cell response to cardiac injury [5]. Therefore, as suggested by Cannata et al., age is a significant risk factor for both more extensive donor heart injury during storage and transport and diminished reanimation and resuscitation by the recipient. Most surgical investigators believe that modifying the preservation solution will reduce ischaemic injury and hasten the recovery of ventricular function after cardiac transplantation. Unfortunately, as illustrated in this paper, the results have been conflicting. As identified in this paper, a recent review of the registry results suggested that the University of Wisconsin solution produced the best outcomes, but both the Celsior solution and the Custodiol (histidine–tryptophan–ketoglutarate, HTK) solution have been suggested to provide the best donor heart protection. Because aged donor hearts have an increased risk of early graft failure, solutions should be evaluated for these hearts. A recent study demonstrated that the HTK solution provided better protection for aged donor hearts than Celsior [6]. Obviously, no consensus has been reached, suggesting that none of the preservation solutions are clearly superior. The Milan group is entirely correct that the choice of the solution may be left to the surgeon. None of the currently available solutions seem to be better than the others. However, surgical investigators are encouraged to determine which solution provides optimal protection for older donor hearts as suggested by the Pittsburgh group (Lee et al.) [6]. If the currently available preservation solutions do not improve donor preservation, what about additives? Preconditioning is the most powerful endogenous protection from ischaemic injury and multiple additives have been evaluated to induce the preconditioning effect in donor hearts [7, 8]. Unfortunately, none of these additives has been demonstrated to be substantially better than cold storage to prevent ventricular dysfunction after transplantation. Determining the potential benefits of a new approach to donor heart preservation remains challenging, as demonstrated by this study from Milan. The factors influencing early biventricular failure include pulmonary vascular resistance, recipient age and previous cardiac surgery. None of these factors is easily modified with improved methods of donor preservation. In their study, Cannata et al. suggested that with 19 events in 133 patients they had the power to detect a 100% relative increase in early mortality. Because of the inherent variability in the factors influencing the recovery of ventricular function, only multi-institutional and probably multi-national studies will be able to demonstrate the benefits of any new approaches. Large studies are difficult to mount and fund, but they may be necessary to improve donor heart protection. Although alternate storage solutions and multiple donor heart additives have not gained acceptance, the future is not bleak. Perfusion of the donor heart offers the promise to resuscitate and rejuvenate hearts from old donors for implantation into old recipients. Donor blood perfusion was demonstrated to be superior to cold storage [9], but the delivery systems were not ideal. Newer technology is now available. Clinical trials are now proceeding to evaluate perfusion systems for donor heart preservation (such as the PROCEED II trial evaluating the Transmedic Organ Care System or trials evaluating the LifeCradle Sytem from Organ Transport Systems). These new approaches may permit the evaluation and rejuvenation of aged donor hearts which can then be used even in aged recipients. However, the challenges of donor heart perfusion should not be underestimated. As reviewed by the group at the University of Maryland (Collins et al.) [10] ‘the best perfusate and perfusion parameters needed to achieve optimal results remain unclear’. The future of donor heart preservation is bright, but substantial challenges remain. The report from Cannata et al. illustrates the need for improved methods of donor heart preservation and demonstrates that choosing an alternate solution may not be the answer. Perfusion during transport may permit resuscitation and rejuvenation of aged donor hearts.

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