Since the first heart transplantation in 1967, improved medical care and immunosuppression have dramatically improved immediate- and long-term outcomes for transplant recipients. While historically, most patients undergoing orthotopic heart transplantation had end-stage ischaemic or dilated cardiomyopathy, the proportion of patients with congenital heart disease (CHD) has increased . However, practitioners remain reluctant to perform heart transplantation in patients with CHD.

In children, because of improvements in diagnosis and treatment, and mostly because of the advances in modern heart surgery, heart transplantation indications have evolved over the past 30 years from a primary indication for treatment of neonates to the treatment of heart failure (HF) in young adults with palliated CHD. Heart transplantation is now rarely considered in the initial management of lesions in children. However, many survivors of infant heart surgery for CHD are not cured, and residual abnormalities in cardiac structure and function predispose adults with congenital heart disease (ACHD) to late-onset HF. Thus, advances in medical and surgical therapy have shifted the problem of heart transplantation to adulthood. Indeed, the number of children transplanted has remained relatively stable over the past 10 years, while the overall proportion of ACHD who are transplanted has increased from 2% in 1992–2003 to 3.3% in 2009–2014, reflecting the growing population of late survivors of CHD surgery .

With 5.1 million Americans affected, HF is the new scourge. Overall survival has improved over time, as a result of advances in medical management . In CHD, HF contributes significantly to late morbidity, and is the leading cause of death, estimated at 26% . Unfortunately, new medical and device therapies developed for adult patients with acquired HF have not been proven to be efficacious for the treatment of HF in patients with CHD . Thus, heart transplantation often remains the only viable treatment option. But ACHD candidates have unique characteristics (complex anatomy, specific physiology, previous interventions, allosensitization) that can make it challenging to perform assessment and clinical management for heart transplantation. While advances in preoperative, operative and postoperative care have been beneficial for most cardiac diseases, such as cardiomyopathy (median survival in 1982–1991, 9.6 years; in 1992–2001, 11.6 years) and coronary artery disease (median survival in 1982–1991, 8.0 years; in 1992–2001, 9.7 years), the median survival for CHD recipients has not improved over the years (median survival in 1982–1991, 14.4 years; in 1992–2001, 13.1 years), and 1-year survival in ACHD recipients remains one of the lowest, ranging from 20% to 32% . There is still a concern over whether it is legitimate to transplant patients whose early outcomes are so alarming in an era of donor shortage, while advances in medical care have led to a reduction in morbidity and mortality in other patients. If ACHD candidates are at such high risk, should we exclude them from the waiting list and invest instead in patients with a better chance of survival to optimize the limited pool of organs? On the other hand, shouldn’t we put these results into perspective?

In the International Society for Heart and Lung Transplantation (ISHLT) registry, CHD is identified as one of the strongest risk factors for 1-year mortality after heart transplantation in adults . In contrast, ACHD recipients have the best conditional survival to 1 year (20.2 years vs. 14.1 years for cardiomyopathy), and the highest overall survival compared with most cardiac diseases resulting in heart transplantation (14.6 years vs. 11.6 years for cardiomyopathy) . ACHD recipients who survive the early postoperative period will have long-term outcomes that are as good as, or even better than, patients with acquired diseases. This early risk reflects the challenges associated with technical difficulties (additional surgical reconstruction procedure, reinterventions for haemostasis) and specific comorbidities, such as pulmonary hypertension, elevated venous pressure, coagulopathy and chronic liver disease. Thus, considering early results should not deprive patients of a treatment that improves their survival and quality of life.

Since the first ligation of patent ductus arteriosus, physicians who specialize in the treatment of CHD have constantly pushed the boundaries of what is possible to save the lives of “their” children, by being more and more inventive, using prostaglandin to dilate the ductus, palliating the univentricular heart, switching the great arteries, transferring the coronary arteries in neonates or opening and replacing valves by catheterism. More and more children who would otherwise have died of their complex CHD have reached adulthood as a result of these medical advances. Thus, those adult patients and their physicians are used to risky and uncertain therapeutic choices, believing, irrationally sometimes, that everything is possible. Unexpectedly, this group of patients with the most complex anatomy also represents those at the highest risk of severe HF and at higher risk of death after heart transplantation. Single ventricle and systemic right ventricle are the most common conditions among ACHD patients undergoing heart transplantation . Even if it is not unanimously recognized, the prevalence of complex ACHD recipients is increasing, reflecting trends in the general population . The effect of these trends on heart transplantation outcomes has been studied in a recently published article . A total of 100 of 2257 heart transplantations (4.4%) were performed in 97 ACHD patients between 1988 and 2012. According to the 32nd Bethesda Conference , 74% had a diagnosis of great complexity. Thirty-three patients died within 30 days of heart transplantation or before being discharged, and 1-year survival was low (64%) despite a large degree of experience in the three centres. Survival rates also did not improve over time, which may be explained by the changing profile of CHD recipients. Although the proportion of complex ACHD has not changed significantly in the recent era, ACHD recipients now have more advanced disease, as evidenced by a greater proportion of inotrope-dependent or United Network for Organ Sharing status 1 patients, and by the increasing number of preoperative assist devices; this might reflect the longer time lag for ACHD patients between advanced HF and listing, often because of the challenge in defining symptomatic HF in ACHD. Improvements in the management of heart transplantation recipients are offset by the increasing severity of the ACHD recipients’ condition. In the study by Cohen et al. , the number of biventricular patients with failing systemic right ventricle increased significantly in the recent era, as a result of an increasing incidence of transposition of the great arteries with atrial switch. The distribution of underlying CHD that will require heart transplantation in the future will certainly change again, as strategies in paediatric cardiology and cardiac surgery have changed and are still changing, as evidenced by the arterial switch operations performed in transposition of the great arteries. Meanwhile, the prevalence of survivors of univentricular palliation with total cavopulmonary connection will increase and, in particular, those with a single right ventricle might appear on the waiting list, as children with hypoplastic left heart syndrome are now palliated by the Norwood procedure .

The growing number of ACHD recipients only reflects the tip of the iceberg. Given the increasing prevalence of complex ACHD and the growing burden of HF, it is surprising that still so few ACHD undergo heart transplantation. Heart transplantation is the only way to “get out of the deadlock of HF” in ACHD patients. Obviously, all efforts should be made to improve short-term results. Because of the donor shortage, the real challenge in the coming years will be to find alternative therapies to treat the increasing number of patients who now die from HF, and who might otherwise be candidates for heart transplantation. The recent American statements on HF, transplantation and mechanical circulatory support in CHD highlighted the limited data to guide the diagnosis and treatment of HF in the ACHD population . The evidence for transposing established HF therapy to ACHD is lacking. But above all, the gap between CHD and non-CHD patients is increasing in the field of mechanical circulatory support, with only 3% of ACHD patients receiving an assist device at the time of heart transplantation ; as a bridge to transplantation, it may decrease the incidence of recipient comorbidities, such as renal dysfunction, mechanical ventilation and malnutrition, and allow for rehabilitation. Unfortunately, technical difficulties and anatomical considerations compromise the use of mechanical support devices in CHD populations: most devices are not designed for implantation in a morphologic left ventricle, and even less in a univentricular physiologic heart. Also, numerous previous surgical interventions make re-entry risky. Regrettably, the use of mechanical circulatory support in acquired heart disease results in a more complex management of priorities on the waiting list, disadvantaging the CHD population. Thus, designing mechanical support devices that are suitable for this heterogeneous population and as a destination therapy is the new Holy Grail in the field of HF.

The requirement for heart transplantation in CHD is likely to increase; as the majority of affected children now survive into adulthood and may develop HF. Heart transplantation is an extraordinary treatment for an ordinary and common situation. As in the past, significant and innovative progress will be necessary to put an end to the new burden of HF in CHD.