Discussion

Over the last 22 years, there has been a progressive decrease in the number of donor hearts suitable for infant recipients in the UK. However, despite the fact that in recent years, there have been only one third the number of donors as previously, the number of transplants performed is largely unchanged and has even increased slightly from 12 in the first decade studied to 16 in the more recent era in keeping with increased demand. Therefore, the overall strategy in this field to increase the probability of successful transplantation for infants in end-stage cardiac failure has succeeded despite the reduction in suitable donors. We have seen a progressively large decrease in the number of potential donors per year since 2000 with now on average less than 10 suitably sized organs available for infant heart transplants per year. The reasons for this fall in donor numbers are unclear but may be related to a number of factors. A welcome reason is the significant decrease in the number of deaths resulting from road traffic accidents due to implementation of seat belt and car seat legislation as well as more stringent speed controls.4 Negative media publicity in the UK around that time surrounding surgical outcomes and the unauthorised retention of human tissue14 15 could also be postulated to have had an effect. There is currently a move towards increasing public awareness of the need for donor organs through the use of the media, the impact of which remains to be seen.

Referrals for assessment and subsequent listing for cardiac transplantation in infancy have increased substantially in recent years with improved awareness of results of transplantation among affected families and the paediatric cardiologists looking after these patients. In our experience, the majority of cardiac transplants in infancy are performed for cardiomyopathy with patients with congenital heart disease rarely being listed for transplant without previous surgical palliation. Improved results of palliation for single ventricle conditions such as hypoplastic left heart syndrome has led to a delay in these patients requiring consideration for transplant.16

The increased demand on transplant services and the fall in donor numbers in the last decade has required a change in strategy—we are now performing more ABO-incompatible and size-mismatched transplants in order to increase the available donor pool and infants are able to be placed on mechanical support while awaiting transplant. For this reason, despite the fall in donors, the number of transplants carried out in this group has remained relatively steady and even increased over time.

In the infant group, there is the possibility of performing up to a 3:1 size-mismatch transplant without a significant increase in postoperative complications.8 17 The use of larger donors potentially increases the available donor pool, and in our cohort of patients, donors have weighed an average of almost three times as much as recipients in recent years.

Initial work from the Hospital for Sick Children in Toronto in the late 1990s demonstrated the feasibility of ABO blood group incompatible transplantation in infants and showed that this is well tolerated in infants with relatively immature immune systems and low isohaemagluttinin titres.5 6 18 This procedure has now become increasingly adopted outside of Canada and between February 2000 and November 2006; 21 ABO-incompatible cardiac transplants were performed in the UK in children aged 2–40 (median 10) months.7 Seven infants in our institution received ABO-incompatible transplants during the study period, with no episodes of humoural rejection. This practice further widens the available donor pool for smaller infants and younger children and is likely to have a significant effect on waiting times for transplantation both on and off mechanical support.

There is now increasing experience and improved results with mechanical support in the paediatric age group,9 13 and between 1998 and 2008, 48 children were supported in our institution. Veno-arterial ECMO10 19 is a widely accepted means of supporting infants once traditional therapies have failed, although often with high mortality, and has been used in our institution since 1998. Complications on ECMO especially related to anticoagulation, infection and neurological events increase exponentially with time,10 and for this reason, it is no longer looked at as long-term support for infants on the waiting list for cardiac transplantation.

The introduction of the pulsatile VADs, in particular the Excor Berlin Heart, has enabled us to support infants more safely and for longer periods than with ECMO.9 11 12 The incidence of neurological complications on mechanical support varies from 15% to 40% in some series9 20 most often in the form of cerebral infarction due to systemic embolisation. Anticoagulation, especially with warfarin, remains a challenge for smaller infants but has proven to be feasible long-term especially in older children.9 12 In our experience, we have been able to manage selected patients outside of the intensive care setting. One of our listed infants was supported with a biventricular assist device but was able to be explanted and delisted after 120 days of support. Only two patients have died while listed since 2005, and the current mechanical support strategies employed may have led to this decrease in waiting list mortality.

In our experience, there has been a decrease in time spent on the waiting list for those infants successfully transplanted which may not mirror the trend in other age groups. This suggests that the use of ABO and size-mismatched transplants have had a bigger influence on waiting times than the potentially increased support times allowed by the use of mechanical devices. The percentage of patients who died while on the waiting list, however, has increased almost threefold. ECMO is time-limited due to complications of bleeding and infection as outlined above, but there is greater hope for improved outcomes and reduced mortality with the Berlin Heart especially in the infant group. Results in infants <1 year of age with the Berlin Heart in our institution are comparable with results in children aged 1-5 years with no excess respiratory or neurological morbidity.9 International results and in particular those of the Berlin Heart Institute support this with survival of over 70% in infants.

There were a substantial number of patients delisted in the second era of our study. This may reflect a trend towards earlier listing for cardiac transplantation in the context of improved long-term outcomes post-transplant or change in the listing criteria with more infants listed earlier in the course of their disease. There has been a decrease in time from onset of symptoms to listing, and although numbers are relatively small and this was not statistically significant, it may reflect current practice. One does, however, also need to consider whether or not it was appropriate to list these infants in the first place. Five of the six delisted patients in our series had an acute dilated cardiomyopathy, and it is known that in patients who improve, complete recovery of left ventricular systolic function is often delayed to more than a year from presentation.21 This, therefore, has implications for timing of transplantation, and an argument could be made that if waiting times are dramatically reduced, we run the risk of transplanting patients who may otherwise have recovered.

Results of cardiac transplantation continue to improve, with the majority of infants now surviving long term.1 22 23 There has been a significant reduction in postoperative mortality in all series1 2 24 which is mirrored in our results. The significant decrease in post-transplant deaths, especially early, due to improved surgical results, is related to increasing experience, especially with transplantation for congenital heart disease. The International Society for Heart and Lung Transplantation Registry Eleventh Annual Paediatric Report has shown a high 1-year survival of 87% in the years 2000–2006 (improved from 71% in the years 1982–1989) with an overall calculated graft half-life of 15.8 years for patients transplanted in infancy.1 In this age group, there appears to be a higher early mortality post-transplantation but lower late mortality as well as a relative sparing from episodes of rejection and coronary artery vasculopathy.24 One of the problems seen in this group is poor development of the immune system; therefore, these patients are prone to recurrent, often respiratory, infections.25 There does not, however, appear to be an increase in post-transplant lymphoproliferative disease in patients transplanted during infancy.1 2

In conclusion, time spent on the waiting list has decreased in the infant group, but there remains a shortage of donors of smaller organs and mortality while waiting for transplant has gone up significantly. The reduction of donor offers is of major concern, but its effect to date appears to have been partly circumvented by the introduction of ABO-incompatible transplants, size-mismatching and improving results with mechanical support of smaller patients. The significant advances in these strategies has, therefore, enabled service levels to be maintained leading to relatively constant or increasing numbers of successful infant transplants.