78
R. Abuanzeh et al. / European Journal of Cardio-Thoracic Surgery
EDITORIAL COMMENT
European Journal of Cardio-Thoracic Surgery 47 (2015) 78–79 doi:10.1093/ejcts/ezu195 Advance Access publication 15 May 2014
Cite this article as: Dark JH. Safe and effective use of the extended donor heart. Eur J Cardiothorac Surg 2015;47:78–79.
Safe and effective use of the extended donor heart John H. Darka,b,* a b
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, UK
* Corresponding author. Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK. Tel: +44-191-2231450; fax: +44-191-2231152; e-mail: [email protected] ( J.H. Dark).
Keywords: Heart transplantation • Organ donor • Donor management • Early donor management
Although an oft-repeated mantra, it does remain absolutely the case that cardiac transplantation is the best, gold standard, treatment for end-stage cardiac failure. Despite the advances in mechanical circulatory support devices (MCSDs), there is still a clear survival advantage from transplantation for most categories of patients [1]. In the current epidemic of heart failure, demand is increasing in all western countries. Although waiting list mortality has fallen as a result of better allocation and particularly MCSDs, the latter just serve to further increase the recipient pool. But on the other side of the coin, the donor hearts for our recipient group are disappearing [2]. Increasingly, organ donors die as a result of intracerebral haemorrhage (as opposed to, for instance, trauma) with cardiovascular comorbidities ranging from untreated hypertension, with left ventricular hypertrophy (LVH), to coronary disease. They are also becoming older, especially in Europe, where the median age of a heart donor is already approaching 45, at least a decade more than in the USA. This age itself has a relative risk of 1.25 for 1-year mortality, compared with the average in the ISHLT registry [3]. A third factor is the fear of primary graft dysfunction. Most early deaths are from sepsis or multiorgan failure, but they are the consequence of failure of the newly implanted heart to pump well. All the bad things in the donor—LVH, age and increased ischaemic time—are related to graft dysfunction. Our challenge is to maximize utilization of donor hearts while avoiding the consequence of poor decisions—a heart that does not function well and kills the recipient. One of the best routes to this end is demonstrated in the paper by Abuanzeh et al. [4] from Manchester in this issue. They have built on research done by the senior author [5], but brought it into routine clinical practice. The principles are well known. Brain stem death has a variety of deleterious effects on the heart, from cathecholamine stress, acute subendocardial ischaemia, right ventricular stretch, loss of vascular tone to inflammatory activation. Circulating proinflammatory cytokines, such as TNF-alpha, have a direct myocardial suppressant effect. In addition, management of the severely brain-injured patient, particularly the maintenance of perfusion pressure with noradrenaline, may worsen the situation. Filling pressures may also be affected by vigorous diuresis, and then diabetes insipidus.
Because of the vulnerability of the right ventricle, right atrial pressures do not give the whole story. The optimization of vascular resistance can only be achieved by measurement of flow in addition to pressure, and with the need to see what is happening on the left side, the pulmonary artery (PA) catheter, used within a simple algorithm, is the best tool. The group in Manchester shows that substantial numbers of hearts that initially fall short of requirements can be improved to a state where they can be used very successfully. If repeated throughout the country, or across a continent, they would have a major impact on transplant numbers. Importantly, albeit in small numbers, this is achieved without jeopardizing outcomes. There are inevitably unanswered questions: One of the advantages is simply the provision of data—accurate figures for flow and pressure. Why cannot all of this be done by the intensive therapy unit (ITU) team managing the donor? There has to be, crucially, an acceptance that the emphasis switches from recovery of the patient towards recovery of organs, once brain death is declared and consent for donation obtained. This may be a difficult change for the ITU team. The incoming, transplant-based clinician can devote all his or her energy to the one patient, and has skills, particularly with the PA catheter, which are increasingly absent in many general or neuro ITUs. But there are obviously circumstances, where all of the input can be achieved locally. Another issue is that of coronary disease. This was only detected by palpation and was the cause of rejection of a third of the unused hearts. It was shown a decade ago that minor, singlevessel palpable disease almost never indicated intralumenal narrowing, and that these hearts can be safely used [6]. For the older donor, angiography has to be a part of assessment. But importantly, there has to be agreement that minor disease is not a contraindication to retrieval. Finally, there is the issue of the timing of retrieval. The heart recovers from much of the insult of brain death, as long as the donor can be stabilized and supported. There is a wealth of literature suggesting that the later after brain death retrieval occurs, the greater the yield of organs. In one large study from the USA, only 20% of donors had hearts used for transplant if the retrieval was within 24 h of brain death. This increased to more than 50% at 36 h [7]. A key to increasing donation rates for hearts, and
R. Abuanzeh et al. / European Journal of Cardio-Thoracic Surgery
REFERENCES [1] Singh TP, Milliren CE, Almond CS, Graham D. Survival benefit from transplantation in patients listed for heart transplantation in the United States. J Am Coll Cardiol 2014;63:1169–78. [2] MacGowan GA, Parry G, Schueler S, Hasan A. The decline of heart transplantation in the UK. BMJ 2011;342:2483.
[3] Lund L, Edwards LB, Kucheryavaya AY, Dipchand AI, Benden C, Christie JD et al. The registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report—2013; Focus Theme: Age. J Heart Lung Transplant 2013;32:951–64. [4] Abuanzeh R, Hashmi F, Dimarakis I, Khasati N, Machaal A, Yonan N et al. Early donor management increases the retrieval rate of hearts for transplantation in marginal donors. Eur J Cardiothorac Surg 2015;47:72–7. [5] Venkateswaran RV, Steeds RP, Quinn DW, Nightingale P, Wilson IC, Mascaro JG et al. The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial. Eur Heart J 2009;30:1771–80. [6] Abid Q, Parry G, Forty J, Dark JH. Concurrent coronary grafting of the donor heart with left internal mammary artery: 10 year experience. J Heart Lung Transplant 2002;21:812–4. [7] Inaba K, Branco BC, Lam L, Salim A, Talving P, Plurad D et al. Organ donation and time to procurement: late is not too late. J Trauma 2010;68: 1362–6.
TX & MCS
probably for all organs, across Europe, is to delay retrieval until there is recovery from the storm surrounding brain death. This requires education of the public, of the intensive care community and the transplant teams. But coupled with the sort of approach taken by the Manchester group, the benefits for our recipients could be substantial and lasting.
79
R. Abuanzeh et al. / European Journal of Cardio-Thoracic Surgery
EDITORIAL COMMENT
European Journal of Cardio-Thoracic Surgery 47 (2015) 78–79 doi:10.1093/ejcts/ezu195 Advance Access publication 15 May 2014
Cite this article as: Dark JH. Safe and effective use of the extended donor heart. Eur J Cardiothorac Surg 2015;47:78–79.
Safe and effective use of the extended donor heart John H. Darka,b,* a b
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, UK
* Corresponding author. Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK. Tel: +44-191-2231450; fax: +44-191-2231152; e-mail: [email protected] ( J.H. Dark).
Keywords: Heart transplantation • Organ donor • Donor management • Early donor management
Although an oft-repeated mantra, it does remain absolutely the case that cardiac transplantation is the best, gold standard, treatment for end-stage cardiac failure. Despite the advances in mechanical circulatory support devices (MCSDs), there is still a clear survival advantage from transplantation for most categories of patients [1]. In the current epidemic of heart failure, demand is increasing in all western countries. Although waiting list mortality has fallen as a result of better allocation and particularly MCSDs, the latter just serve to further increase the recipient pool. But on the other side of the coin, the donor hearts for our recipient group are disappearing [2]. Increasingly, organ donors die as a result of intracerebral haemorrhage (as opposed to, for instance, trauma) with cardiovascular comorbidities ranging from untreated hypertension, with left ventricular hypertrophy (LVH), to coronary disease. They are also becoming older, especially in Europe, where the median age of a heart donor is already approaching 45, at least a decade more than in the USA. This age itself has a relative risk of 1.25 for 1-year mortality, compared with the average in the ISHLT registry [3]. A third factor is the fear of primary graft dysfunction. Most early deaths are from sepsis or multiorgan failure, but they are the consequence of failure of the newly implanted heart to pump well. All the bad things in the donor—LVH, age and increased ischaemic time—are related to graft dysfunction. Our challenge is to maximize utilization of donor hearts while avoiding the consequence of poor decisions—a heart that does not function well and kills the recipient. One of the best routes to this end is demonstrated in the paper by Abuanzeh et al. [4] from Manchester in this issue. They have built on research done by the senior author [5], but brought it into routine clinical practice. The principles are well known. Brain stem death has a variety of deleterious effects on the heart, from cathecholamine stress, acute subendocardial ischaemia, right ventricular stretch, loss of vascular tone to inflammatory activation. Circulating proinflammatory cytokines, such as TNF-alpha, have a direct myocardial suppressant effect. In addition, management of the severely brain-injured patient, particularly the maintenance of perfusion pressure with noradrenaline, may worsen the situation. Filling pressures may also be affected by vigorous diuresis, and then diabetes insipidus.
Because of the vulnerability of the right ventricle, right atrial pressures do not give the whole story. The optimization of vascular resistance can only be achieved by measurement of flow in addition to pressure, and with the need to see what is happening on the left side, the pulmonary artery (PA) catheter, used within a simple algorithm, is the best tool. The group in Manchester shows that substantial numbers of hearts that initially fall short of requirements can be improved to a state where they can be used very successfully. If repeated throughout the country, or across a continent, they would have a major impact on transplant numbers. Importantly, albeit in small numbers, this is achieved without jeopardizing outcomes. There are inevitably unanswered questions: One of the advantages is simply the provision of data—accurate figures for flow and pressure. Why cannot all of this be done by the intensive therapy unit (ITU) team managing the donor? There has to be, crucially, an acceptance that the emphasis switches from recovery of the patient towards recovery of organs, once brain death is declared and consent for donation obtained. This may be a difficult change for the ITU team. The incoming, transplant-based clinician can devote all his or her energy to the one patient, and has skills, particularly with the PA catheter, which are increasingly absent in many general or neuro ITUs. But there are obviously circumstances, where all of the input can be achieved locally. Another issue is that of coronary disease. This was only detected by palpation and was the cause of rejection of a third of the unused hearts. It was shown a decade ago that minor, singlevessel palpable disease almost never indicated intralumenal narrowing, and that these hearts can be safely used [6]. For the older donor, angiography has to be a part of assessment. But importantly, there has to be agreement that minor disease is not a contraindication to retrieval. Finally, there is the issue of the timing of retrieval. The heart recovers from much of the insult of brain death, as long as the donor can be stabilized and supported. There is a wealth of literature suggesting that the later after brain death retrieval occurs, the greater the yield of organs. In one large study from the USA, only 20% of donors had hearts used for transplant if the retrieval was within 24 h of brain death. This increased to more than 50% at 36 h [7]. A key to increasing donation rates for hearts, and
R. Abuanzeh et al. / European Journal of Cardio-Thoracic Surgery
REFERENCES [1] Singh TP, Milliren CE, Almond CS, Graham D. Survival benefit from transplantation in patients listed for heart transplantation in the United States. J Am Coll Cardiol 2014;63:1169–78. [2] MacGowan GA, Parry G, Schueler S, Hasan A. The decline of heart transplantation in the UK. BMJ 2011;342:2483.
[3] Lund L, Edwards LB, Kucheryavaya AY, Dipchand AI, Benden C, Christie JD et al. The registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report—2013; Focus Theme: Age. J Heart Lung Transplant 2013;32:951–64. [4] Abuanzeh R, Hashmi F, Dimarakis I, Khasati N, Machaal A, Yonan N et al. Early donor management increases the retrieval rate of hearts for transplantation in marginal donors. Eur J Cardiothorac Surg 2015;47:72–7. [5] Venkateswaran RV, Steeds RP, Quinn DW, Nightingale P, Wilson IC, Mascaro JG et al. The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial. Eur Heart J 2009;30:1771–80. [6] Abid Q, Parry G, Forty J, Dark JH. Concurrent coronary grafting of the donor heart with left internal mammary artery: 10 year experience. J Heart Lung Transplant 2002;21:812–4. [7] Inaba K, Branco BC, Lam L, Salim A, Talving P, Plurad D et al. Organ donation and time to procurement: late is not too late. J Trauma 2010;68: 1362–6.
TX & MCS
probably for all organs, across Europe, is to delay retrieval until there is recovery from the storm surrounding brain death. This requires education of the public, of the intensive care community and the transplant teams. But coupled with the sort of approach taken by the Manchester group, the benefits for our recipients could be substantial and lasting.
79
