Outcome after heart transplantation from older donor age: expanding the donor pool

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1 European Journal of Cardio-Thoracic Surgery 47 (2015) doi: /ejcts/ezu257 Advance Access publication 9 July 2014 ORIGINAL ARTICLE Cite this article as: Prieto D, Correia P, Baptista M, Antunes MJ. Outcome after heart transplantation from older donor age: expanding the donor pool. Eur J Cardiothorac Surg 2015;47: Outcome after heart transplantation from older donor age: expanding the donor pool David Prieto, Pedro Correia, Manuel Baptista and Manuel J. Antunes* Center of Cardiothoracic Surgery, University Hospital and Medical School, Coimbra, Portugal * Corresponding author. Centro de Cirurgia Cardiotorácica, Hospitais da Universidade, Coimbra, Portugal. Tel: ; fax: ; antunes.cct.huc@sapo.pt (M.J. Antunes). Received 12 March 2014; received in revised form 8 May 2014; accepted 20 May 2014 Abstract OBJECTIVES: There has been a progressive expansion of heart donor selection criteria, including higher age limit. We analysed the impact of using hearts from older age donors (>50 years). METHODS: Between November 2003 and December 2012, 228 heart transplantations were performed. Children and patients requiring ventricular assistance prior to transplantation were excluded. Recipients from 26 donors aged 50 years (Group A) were compared with those of 136 donors <40 years (Group B). Patient and donor criteria were identical in both groups. RESULTS: Group A recipients were older than those in Group B (59 ± 11 vs 53 ± 11; P < 0.01), and tended to have more ischaemic cardiomyopathy (50 vs 35%; P = 0.16), be in intensive care (31 vs 27%; P = 0.65) and have longer waiting time (56 ± 49 vs 41 ± 47 days; P = 0.15). There were also significant differences in ischaemic time (65 ± 27 vs 93 ± 35 min; P < 0.01). Thirty-day mortality was similar (3.8 vs 3.7%; P = 0.97). Follow-up was 55 ± 32 months. Actuarial survival at 1, 3 and 5 years was 84 ± 7% for Group A and 90 ± 3, 86 ± 3 and 81 ± 4%, respectively, for Group B (P = 0.85). There were no survival differences between patients younger and older than 60 years, but there was a tendency for decreased survival free from cardiac allograft vasculopathy (CAV) in Group A compared to Group B (at 8 years 65 ± 18 vs 78 ± 7%; P = 0.06). CONCLUSIONS: Parameters of exclusion of donor hearts can and must be adjusted, since the use of selected marginal donors associated with short ischaemic times appears to have no negative impact on morbidity and mortality, more importantly when compared with mortality on the waiting list. Keywords: Heart transplantation Old donors Outcome Allograft vasculopathy INTRODUCTION Cardiac transplantation offers a definitive therapy for patients with end-stage congestive heart failure and leads to greatly improved survival and quality of life. However, this surgical therapy is increasingly limited by a continuous donor organ shortage. Today, a high number of patients on the list do not reach transplantation, living the final part of their life under extremely uncomfortable physical and psychological conditions [1]. This chronic shortage of suitable donor organs and an increasing demand for cardiac transplantation has led to many forms of expansion of donor acceptance criteria [2, 3], including the use of hearts from selected older donors. The upper limit of donor age, initially placed at around the 40-year limit, has been increasing year after year [4, 5]. However, there are still controversial reports on the impact this practice might have in the results of heart transplantation with regard to morbidity and early and late survival [6, 7]. The objective of this study was to investigate post-transplantation outcomes in recipients of older donor hearts in a single centre and to determine if older donor age ( 50 years) is associated with an increased risk of early and late morbidity and mortality, and survival. MATERIALS AND METHODS A retrospective analysis was performed of patients undergoing orthotopic heart transplantation at the Coimbra University Hospital. From November 2003 through December 2012, 228 heart transplantations were performed. Paediatric patients (4%) and patients with cardio-circulatory assistance (extracorporeal membrane oxygenation (ECMO), intra-aortic balloon, mechanical ventilator 3%) immediately before the transplantation or those previously treated with other organ transplantation (1%) were excluded from this study. Patients who received hearts from donors between 40 and 49 years old (n = 48; 23%) were not included in this analysis for the sake of a clearer distinction between groups. Nevertheless, no major differences were found in this particular group regarding patients characteristics or clinical outcomes, when compared with recipients of younger hearts. Donor and patient data were prospectively collected and retrospectively analysed from a dedicated institutional database, inserted in the national registry. Hearts from donors at least 50 years of age (range years; mean 52 ± 2 years) were used in 26 patients (16%). These patients The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 D. Prieto et al. / European Journal of Cardio-Thoracic Surgery 673 (Group A) were compared with 136 patients who received organs from donors <40 years of age (range years; mean 28 ± 7 years Group B). Among the 162 patients analysed, 44 (27%) were in high surgical priority (urgency patients in intensive care and submitted to inotropic perfusion for worsening heart failure). Other patient and donor selection criteria were identical for both groups. Donor procurement All hearts were harvested from beating-heart brain-dead donors. When selecting older donors, special interest was given to the estimated time of ischaemia, the cause of death and the length of admission to hospital and inotropic perfusion in intensive care units (ICUs). Donor assessment was based on clinical and laboratorial evaluation and transthoracic echocardiography, available in all cases. Coronary angiography was generally requested in males older than 45 years and females older than 50 years, or in younger donors with significant risk factors for cardiovascular disease. Less than 10% of the hearts were rejected because of significant coronary disease. Three hearts with palpable plaques but no significant luminal stenosis were used, including one from a patient who received a mammary artery graft. Because a preoperative coronary angiogram was not available at the donor hospital in 8 cases (31%), the segmental analysis by preharvesting echocardiogram and visual and digital inspection of the heart made by the harvesting surgeon helped in making the final decision. Harvesting of the heart was limited to experienced surgeons belonging to the same transplantation team. All allografts were protected by 1 l of cold (4 C) cardioplegic solution (Celsior ), perfused antegrade in the aortic root and immersed in a cold solution of physiological saline (topical hypothermia) during transportation. Surgical technique All transplantations were performed using the bicaval method, under cardiopulmonary bypass and moderate systemic hypothermia (28 C). To shorten ischaemic time, pulmonary vein anastomosis, as a button, and the aortic anastomosis were performed first, immediately followed by unclamping of the aorta. The remaining anastomoses were done under coronary perfusion. For its chronotropic effect, all patients received an infusion of dobutamine (5 µg/ kg) after all the anastomoses were completed. The need for further inotropic support or post-transplantation mechanical assistance was determined after a period of adequate reperfusion, and this decision was based on intraoperative visualization of the heart, haemodynamic signs and transoesophageal echocardiogram (TOE). Of note, concomitant mitral valvuloplasty was performed in 6 donor hearts previously known to have moderate mitral valve disease, 2 in Group A and 4 in Group B, as another gesture to expand the numbers of donors. dose-adjusted to blood levels assessed by monoclonal fluorescence polarization immunoassay), mycophenolate mofetil (1 g twice daily) and steroids (125 mg of methylprednisolone intravenously every 8 h for 3 days postoperatively), followed by prednisone (0.8 mg/kg/day during the first week and then tapered off in the subsequent 4 weeks to 0.2 mg/kg per day). Right ventricular endomyocardial biopsies were performed on a routine protocol or when it was considered to be clinically necessary. Diagnosis of acute cardiac rejection was made according to the International Society for Heart and Lung Transplantation (ISHLT) criteria (2004 classification), and was treated if equal to or greater than 2R, with pulse doses of intravenous methylprednisolone (500 mg) for 3 days, and optimization of the dose of oral immunosuppressive drugs. Early postoperative allograft performance was evaluated by echocardiograms, repeated during every outpatient visit and right catheterization, according to the protocol. Coronary angiograms were performed at yearly intervals, or more frequently if clinically indicated. All coronary angiograms were reviewed by a cardiologist and cardiac surgeon, and compared with the previous film to detect the presence of any new luminal irregularities, stenosis or pruning of vessels. Cardiac allograft vasculopathy (CAV) was defined based on the following: new lesions resulting in partial obstruction of major graft vessels or concentric and diffuse narrowing of the whole vessels, including their branches. When that was possible, at post-mortem examination, the heart was inspected for evidence of vessel obstruction or irregularities, ischaemic damage and acute cardiac rejection or infarction. Postoperative care and follow-up The postoperative care was given in a dedicated ICU in the surgical centre and short-term postoperative complications were monitored by the surgical team. Prophylactic antibiotic therapy was discontinued in patients with no sign of infection 4 days after transplantation. For patients with donor CMV positive/recipient CMV positive and for donor CMV negative/recipient CMV positive (low risk), a pre-emptive therapy and monitoring with weekly antigenaemia or PCR-DNA was used. Prophylaxis for high-risk patients covered a minimum of 3 months post-transplantation with Valganciclovir (450 mg twice daily, adjusted for renal function and results of antigenaemia). Patients in whom the first post-transplantation cardiac catheterization showed elevated pulmonary pressure were treated with calcium antagonists, angiotensin-converting enzyme inhibitors and oral sildenafil. Discharge from hospital was usually planned for the 10th 12th day after transplantation. All patients were followed up (end of study follow-up, December 2013) in the outpatient department of the surgical centre by the surgeons, assisted by one dedicated internal medicine specialist. Routine follow-up examinations included echocardiogram, electrocardiogram, blood and serum biochemistry, thorax radiography, titration of serum levels of immunosuppressive drugs and monitoring for cytomegalovirus infection. TX & MCS Immunosuppression and rejection monitoring Routine induction therapy consisted of mycophenolate mofetil (1 g), methylprednisolone sodium succinate (500 mg) and baxilisimab (20 mg) administered pre- and during transplantation. After transplantation, we used a calcineurin inhibitor (mostly cyclosporin, Statistical analysis Continuous variables were reported as mean ± standard deviation (SD) and were compared using Student s t-test for normally distributed continuous variables and the Mann Whitney U-test for non-

3 674 D. Prieto et al. / European Journal of Cardio-Thoracic Surgery Table 1: Demographic and clinical profile of recipients in Groups A and B Recipient Global Donors 50 Donors <40 P-value Group A Group B Recipient age (years, mean ± SD) 54 ± ± ± 11 <0.01 Age range (minimum maximum) Age 60 years (%) 64 (40%) 18 (69%) 46 (34%) <0.01 Gender (male) 128 (79%) 22 (85%) 106 (78%) 0.44 Follow-up (years) 4.6 ± ± ± 2.6 <0.01 Wait-list time (days) 44 ± ± ± BMI mean (kg/m 2 ) 24 ± 3 24 ± 3 24 ± Diabetes 36 (22%) 7 (27%) 29 (21%) 0.53 Essential hypertension 59 (36%) 10 (39%) 49 (36%) 0.81 Dyslipidaemia 74 (46%) 16 (64%) 58 (43%) 0.05 Prior cardiac surgery 49 (30%) 11 (42%) 38 (28%) 0.14 Ischaemic cardiomyopathy 61 (38%) 13 (50%) 48 (35%) 0.16 Dilated cardiomyopathy 63 (39%) 9 (35%) 54 (40%) 0.63 Peripheral vascular disease 57 (35%) 12 (46%) 45 (33%) 0.20 Carotid stenosis 8 (5%) 2 (8%) 6 (4%) 0.48 Cardiac index (l/min/m 2 ) 1.9 ± ± ± Trans-pulmonary gradient (mmhg) 9.5 ± ± ± Pulmonary vascular resistance (UW) 3.4 ± ± ± VO 2 max (ml/kg/min) 14 ± 6 13 ± 2 14 ± Bilirubin (mg/dl) 1.2 ± ± ± Glomerular filtration rate (ml/min) 61 ± ± ± Creatinine level (mg/dl) 1.4 ± ± ± High urgency 44 (27%) 8 (31%) 36 (27%) 0.65 Values in bold indicate statistical significant difference. SD: standard deviation; BMI: body mass index; VO 2 : maximal oxygen consumption; UW: Wood units. normally distributed continuous variables. Normality was accessed by the Kolmogorov Smirnov and Shapiro Wilk tests. Categorical variables were reported as percentages and were compared using χ 2 tests or Fisher s exact test when appropriate. Actuarial survival and event-free survival were plotted using the Kaplan Meier method and the two groups were compared using log-rank analysis. Statistical significance was defined as a two-tailed probability value of P < Data were analysed using the statistical package program SPSS (version 19, SPSS, Inc., Chicago, IL, USA). RESULTS The demographic and clinical data on the patients in the two study groups are detailed in Table 1. The mean age of the recipients was 59 ± 11 vs 53 ± 11 years (P < 0.01). There was no gender difference between the two groups (male 85 vs 78%; P = 0.44). Time on the waiting list was 56 ± 49 vs 41 ± 47 days (P = 0.15). Follow-up extended up to 10 years, with a mean of 39 ± 34 months in the older donor group and 59 ± 31 months in the younger group (P < 0.01). There were no significant differences in the prevalence of risk factors: diabetes mellitus, 27 vs 21%; ischaemic cardiomyopathy, 50 vs 35%; peripheral vasculopathy 46 vs 33%; except for dyslipidaemia 64 vs 43% (P = 0.05). All are recognized as important risk factors involved in the development of the CAV. inotrope requirement for the donor, defined as a sustained need for dopamine 15 µg/kg/min or noradrenaline 1.5 µg/kg/min or inotrope dependency prolonged for more than 1 week, was not different in the two groups (Table 2). There were clear differences among the causes of death of the donor. The main cause in Group A was cerebral vascular accident (69 vs 28%), whereas traumatic cranial injury was more frequent in Group B (31 vs 66%). Surgery and intensive care unit The mean ischaemic time was 89 ± 35 min, with a significant difference between groups (65 ± 26 vs 93 ± 35 min; P < 0.01). In Group A, 58% of the patients had an ischaemic time shorter than 60 min. In comparison, 72% of patients in Group B suffered an ischaemia longer than 60 min, as given in Table 3. Postoperative mechanical ventilation was prolonged in Group A (23 ± 40 vs 18 ± 16 h), but this did not reach statistical significance. Primary graft dysfunction, defined as high-dose inotrope requirement (dobutamine 10 µg/kg/min), lasting for more 24 h or associated with another inotropic and/or mechanical circulatory support (ECMO), was not significantly different between groups (7 vs 11%). Rejection and other morbidity Donors The average age of the donors was 52 ± 2 vs 28 ± 7 years (P < 0.01). No gender differences were found between the two groups. High The main causes of significant morbidity are detailed in Table 4. Acute cellular rejection (ISLHT R) occurred in 30 patients (19%), 12% in Group A and 20% of Group B (P = 0.32). The incidence of acute humoural rejection was similar (4 vs 3%).

4 D. Prieto et al. / European Journal of Cardio-Thoracic Surgery 675 Table 2: Clinical data of donors in Groups A and B Donor Global A B P-value Donor age (years) 32 ± ± 2 28 ± 7 <0.01 Gender, male 35 (22%) 6 (23%) 29 (21%) 0.84 Inotropic dependence >1 week 9 (6%) 2 (8%) 7 (5%) 0.60 Mechanical assistance >1 week 21 (13%) 3 (12%) 18 (13%) 0.81 Donor female/recipient male 26 (16%) 4 (15%) 22 (16%) 0.92 Total sex mismatch 51 (32%) 6 (23%) 45 (33%) 0.31 Cause of death Ischaemic cerebral accident 2 (1%) 1 (4%) 1 (1%) 0.19 Haemorrhagic cerebral accident 54 (33%) 17 (65%) 37 (27%) <0.01 Brain trauma 98 (61%) 8 (31%) 90 (66%) <0.01 Values in bold indicate statistical significant difference. Table 3: Surgery data Surgery Global A B P-value Total ischaemic time (min) 89 ± ± ± 35 <0.01 CPB time mean (min) 98 ± ± ± Time to extubation (h) 19 ± ± ± Inotropic requirement 17 (11%) 2 (8%) 15 (11%) 0.61 Mechanical assistance 7 (4%) 1 (4%) 6 (4%) 0.90 Haemorrhage 6 (4%) 2 (8%) 4 (3%) 0.24 Mitral valvuloplasty 6 (4%) 2 (8%) 4 (3%) 0.24 Values in bold indicate statistical significant difference. CPB: cardiopulmonary bypass. Table 4: Incidence of rejection and other significant morbidity Characteristics Global A B P-value No rejection (0R) a 63 (39%) 8 (31%) 55 (40%) 0.35 Acute cellular rejection 2R a 23 (14%) 2 (8%) 21 (15%) 0.30 Acute cellular rejection 3R a 8 (5%) 1 (4%) 7 (5%) 0.78 Rejection 2R a, before 12 months 26 (16%) 2 (8%) 24 (18%) 0.21 Humoural rejection 5 (3%) 1 (4%) 4 (3%) 0.81 Cardiac allograft vasculopathy 13 (8%) 3 (12%) 10 (7%) 0.47 NODAT b 23 (14%) 3 (12%) 20 (15%) 0.67 Pneumonia 6 months 20 (12%) 3 (12%) 17 (13%) 0.89 Infections 12 months 25 (15%) 4 (15%) 21 (15%) 0.99 TX & MCS a ISHLT (2004). b New-onset diabetes after transplantation (NODAT) within the first year after heart transplantation. The incidence of new onset diabetes after transplantation (NODAT) in the first year post-transplantation was not different (12 vs 15%) between the groups. There was also no difference in the incidence of serious infections, which required hospitalization and intravenous antibiotic treatment, the most frequent being bacterial pneumonia. Mortality and survival There were six deaths (4%) within the first month posttransplantation (cerebrovascular accident, 4; heart failure, 1; allograft rejection, 1). There were no statistically significant differences in the distribution of the causes of early death and the incidence

5 676 D. Prieto et al. / European Journal of Cardio-Thoracic Surgery Table 5: Incidence and causes of mortality Mortality Global A B P-value Global mortality 35 (22%) 5 (19%) 30 (22%) 0.75 Hospital mortality 6 (4%) 1 (4%) 5 (4%) 0.97 Mortality <6 months 16 (10%) 3 (12%) 13 (10%) 0.76 Mortality <1 year 18 (11%) 4 (15%) 14 (10%) 0.45 Cause of death Cardiac 5 (3%) 1 (4%) 4 (3%) 0.81 Vascular 10 (6%) 2 (8%) 8 (6%) 0.73 Malignant tumour 5 (3%) 0 (0%) 5 (4%) 0.32 Neuropsychiatric 3 (2%) 0 (0%) 3 (2%) 0.45 Infection 9 (6%) 1 (4%) 8 (6%) 0.68 of primary graft failure between groups (Table 5). The distribution of causes of late and total deaths (29 patients; 18%) was similar between groups. As illustrated in Fig. 1, 6-month (89 ± 6 vs 90 ± 3%), 1-year (84 ± 7 vs 90 ± 3%), 3-year (84 ± 7 vs 86 ± 3%) and 5-year (84 ± 7 vs 81 ± 4%) survivals for Group A versus Group B patients were not significantly different (P = 0.85). Survival of patients 60 years and older receiving older donor hearts was similar compared with the same age recipients of younger donor hearts (1-year, 83 ± 9 vs 87 ± 5% and 3-year, 83 ± 9 vs 82 ± 6%, P = 0.47) (Fig. 2). There was a tendency for a greater incidence of CAV in patients with older donors (12 vs 7%) and the 5-year survival free from CAV was decreased in this group (82 ± 13 vs 95 ± 2%; P = 0.04), as shown in Fig. 3. DISCUSSION This work is part of a systematic analysis we are conducting to evaluate the outcomes and respective factors of our heart transplantation programme initiated in November In the ensuing 10 years, 258 patients were transplanted, representing approximately two-thirds of the procedures performed in our country during this period [8]. Here, we wanted to measure the impact of utilizing older donor hearts as a measure to help offset organ shortage. Although Portugal is, in this respect, blessed by a legal presumed donor consent situation, this world-wide phenomenon also affects us. The use of the so-called marginal donors is now generally accepted and widespread. Classically, the upper age limit for heart donation was years, but there is no definitive reason why selected older donor hearts cannot be used if structurally normal. This includes additional surgical steps, such as limited mitral valvuloplasty, which was performed in 6 patients in this series, thus contributing to additional donor usage. Generally, patients who received older donor hearts did not have significantly higher rates of postoperative complications than those who received younger hearts and the causes of death late after transplantation, including acute rejection, sepsis and heart failure, were similar between groups. However, the major lesson from our study comes from comparison of survival of the two groups. The 1-year survival was 84 ± 7 vs 90 ± 3%, respectively, for Groups A and B(P = 0.85). Especially important, survival of older patients (>60 Figure 1: Global survival for patients (Pts) of Groups A and B (P = 0.85, log rank). years) receiving older donor hearts was similar to that of recipients of the same age group receiving younger donor hearts. Analysing the clinical profile of the donors in our series, some significant differences were found, especially in the cause of death, ischaemic time, recipient s age and degree of emergency. By protocol, older donor hearts were predominantly implanted in older recipients (59 ± 11 vs 53 ± 11 years; P < 0.01), which could be expected to have an impact on survival. In Group A, the donor main cause of death was CVA (65%), whereas brain trauma prevailed in Group B (66%). CVA may be a surrogate for more generalized cardiovascular disease, including coronary atherosclerosis. Although we managed to obtain a coronary angiography and confirmed the absence of coronary disease in the majority of the donors, small branch disease is difficult to diagnose [9]. Our overall short ischaemic time (89 ± 35 min), partly resulting from the technique used (see above), may be responsible for

6 D. Prieto et al. / European Journal of Cardio-Thoracic Surgery 677 Figure 2: Survival of recipients aged >60 years of Group A and B (P = 0.47, log rank). Pts: patients. Figure 3: Survival free from cardiac allograft vasculopathy (P = 0.17). Pts: patients. reducing the differences in operative and postoperative outcomes, especially during the first month after transplantation [10]. And ischaemic time was significantly lower in Group A, because we deliberately selected older donors from emergency units closer to our centre. As a rule, local donors led to ischaemic times inferior to 45 min and longer distance (mean 120 km) donors to <90 min. In fact, in 58% of patients of Group A, the ischaemic time was <60 min. Some series have demonstrated prolonged donor ischaemic time to be associated with significantly reduced postoperative biventricular function and increased requirement for inotropic support within the first few days post-transplantation. Multiinstitutional studies concluded that prolonged donor ischaemic time was an independent risk factor for early mortality after transplantation [11]. Conclusions were, however, derived from the confluence of data from many institutions, where there may be significant differences in management strategies and experiences. In fact, the results of a single large-institution experience could be confounded by results from smaller centres with significant mortality rates [12]. The overall significance of ischaemic time is also emphasized by the ISHLT registry, which identifies it as an important cause of mortality at 1 year following cardiac transplantation [1]. It appears that the greatest risk from using hearts from older donors is limited to the first month after transplantation [13]. Therefore, efforts should be made to reduce coincident risks. Thus, recipients receiving hearts from older donors should only receive these allografts if the ischaemic time can presumably be short. In any case, one should bear in mind that the survival of transplantation candidates who received hearts from older donors is much superior to that of those who were never transplanted. Hence, it is a worthwhile method to expand the pool of donors [14]. But careful selection of recipients and donors is fundamental. It has been suggested that the risk of development of CAV is greater in older donor cases. A potential explanation for the increased likelihood of the development of CAV is the aetiology of brain death in the donor, said to be especially relevant in trauma cases [15, 16]. Another hypothesis may be a reflection of age-related endothelial dysfunction and recipient cardiovascular risk factors. Cause of death and age may have a relationship beyond expected. Stroke (CVA) is associated to increased age and to other known diseases, mainly hypertension, which will mark, to a greater or lesser degree, the future of the graft. Group A recipients had more ischaemic heart disease, diabetes, hypertension, dyslipidaemia, peripheral vascular disease and carotid stenosis. This is consistent with a higher prevalence of CAV with its multifactorial genesis. Hence, aggressive treatment of hypertension and hypercholesterolaemia may contribute to a lower incidence of CAV. However, with our poor knowledge of the evolution of this disease in older donors, we think it would be prudent to utilize the newer therapies available to prevent rejection (mammalian target of rapamycin inhibitor) in this setting [17]. Among the 162 patients analysed, 44 (27%) with inotropic dependence were placed on high priority, and this rate was 31% of the donor older group. These candidates for transplantation were hospitalized in intensive care for worsening heart failure which would lead them to a rapid end [18, 19]. Hence, they were clearly beneficiaries of the method. Most would have otherwise never reached transplantation if not simply excluded from the waiting list [20, 21]. An added advantage is that, in this way, more young recipients received hearts from younger donors. It should be noted that patients under mechanical or ventilatory assistance were deliberately excluded from this study, which also accounts for the relatively low incidence of high-urgency patients in the study group. We feel that, as special care must be taken when choosing older donors, the recipients must also be carefully TX & MCS

7 678 D. Prieto et al. / European Journal of Cardio-Thoracic Surgery selected for this purpose. We find this as part of the explanation of the good clinical outcome observed. STUDY LIMITATIONS This is a retrospective study, which can always be subject to bias. Ideally, a matching should be made between both groups for important baseline clinical characteristics to draw more powerful conclusions. Unfortunately, the number of patients in the older donor group is not sufficiently large to perform such a study. Nevertheless, we believe that the data presented are sufficient to vindicate the policy of using selected donors older than the age limit usually included in transplantation protocols. CONCLUSION Age has often been a factor for excluding donors. This study, however, shows that donors should not be excluded based solely on age. There was no difference in long-term survival among the recipients of older hearts compared with those who received hearts from younger donors, although there were more patients who developed CAV in the former group. The potential benefits on survival of recipients who received hearts from older donors must be compared with those who never reached transplantation because of lack of donors and so died while waiting. Therefore, our data support the concept that heart transplantation with older donor hearts should be considered, albeit cautiously, in view of the scarcity of organs. However, variables such as donor stability, inotropic use, ischaemic time, left ventricular function and high urgency for transplantation should be considered in the decision to accept these donors. Furthermore, these donors need not be reserved exclusively for older recipients because younger patients may also benefit. We emphasize the association of short ischaemic times with the use of older donors to achieve good clinical outcomes. While stressing the importance of this practice, we also acknowledge the potential difficulty in extrapolating this strategy to other centres with different logistics. Conflict of interest: none declared. REFERENCES [1] Lund LH, 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 J Heart Lung Transplant 2013;32: [2] Jeevanandam V, Furukawa S, Prendergast TW, Todd BA, Eisen HJ, McClurken JB. Standard criteria for an acceptable donor heart are restricting heart transplantation. Ann Thorac Surg 1996;62: [3] Brock MV, Salazar JD, Cameron DE, Baumgartner WA, Conte JV. The changing profile of the cardiac donor. J Heart Lung Transplant 2001;20: [4] Blanche C, Kamlot A, Blanche DA, Kearney B, Magliato KE, Czer L et al. 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