Search

In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic "advantages," including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients' post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding "incentives" such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.

Successful infant heart transplantation has now been performed for over 25 years. Assessment of long term outcomes is now possible. We report clinical outcomes for322 patients who received their heart transplant during infancy. Actuarial graft survival for newborn recipients is 59% at 25 years. Survival has improved in the most recent era. Cardiac allograft vasculopathy is the most important late cause of death with an actuarial incidence at 25 years of 35%. Post-transplant lymphoma is estimated to occur in 20% of infant recipients by25 years. Chronic kidney disease grade 3 or worse is present in 31% of survivors. The epidemiology of infant heart transplantation has changed through the years as the results for staged repair improved and donor resources remained stagnant. Most centers now employ staged repair for hypoplastic left heart syndrome and similar extreme forms of congenital heart disease. Techniques for staged repair, including the hybrid procedure, are described. The lack of donors is described with particular note regarding decreased donors due to newer programs for appropriate infant sleep positioning and infant car seats. ABO incompatible donors are a newer resource for maximizing donor resources, as is donation after circulatory determination of death and techniques to properly utilize more donors by expanding the criteria for what is an acceptable donor. An immunological advantage for the youngest recipients has long been postulated, and evaluation of this phenomenon may provide clues to the development of accommodation and/or tolerance.

Background: An increasing number of children are being referred for cardiac transplantation after (1) failing conventional corrective or palliative surgical reconstruction, (2) after stabilization with mechanical circulatory support devices, and (3) when primary graft failure or advanced cardiac allograft vasculopathy are established., Methods: The records of 417 infants and children (age range, 0-18 years) who underwent cardiac transplantation from November 1985 through December 2005 at Loma Linda University Children's Hospital were retrospectively reviewed. The pre-transplantation diagnosis was used to divide patients into 3 groups: primary cardiomyopathy (CM), 103; hypoplastic left heart syndrome (HLHS), 154; and other complex congenital heart disease (CCHD), 160. These groups were compared and analyzed for differences in early and late morbidity and mortality., Results: Operative mortality was significantly lower in the CM group compared with the HLHS (p < 0.02;) and CCHD groups (p < 0.01). Long-term actuarial recipient survival, however, was similar for all groups. The 15-year actuarial survival was 59% for the CM Group, 57% for the HLHS Group, and 50% for the CCHD Group. Actuarial survival after retransplantation is not statistically different from that with primary cardiac transplantation., Conclusion: Although peri-operative survival was lower in infants and children with HLHS and CCHD compared with those with CM, long-term survival has been the same for all groups. Late survival after retransplantation was not statistically different than among those with primary cardiac transplantation.

The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosuppressive therapy. If one could safely and effectively exploit neonatal tolerance for successful xenotransplantation of the heart, the challenge of severe cardiac failure in the newborn infant might be met. We discuss the need, the potential for applying neonatal tolerance in the setting of xenotransplantation and the possibility that other approaches to this problem might emerge. [ABSTRACT FROM AUTHOR]

To evaluate social development of pediatric heart transplant (tx) recipients who have lived 15 or more years after transplantation. Among 498 pediatric patients, age less than 18 years, who underwent heart transplantation, at a single institution, 337 were performed between 1985 and 1998. We identified all who survived more than 15 years and engaged them in a survey regarding employment, education, marital, and social status. One hundred and eighty-three recipients (54.3%; 183/337) have survived greater than 15 years; of these, 150 (81.9%) subjects are alive with age ranging from 15.04 from 28 years (median, 23.6 years). Forty-two patients (23%) are independent, 127 (69%) were living at home, and 14 (8%) have been lost to follow-up. Ninety-nine survivors (66%) responded to the survey study. Currently, five recipients are married. Seventy-four completed high school, 21 are enrolled in high school, and four did not complete high school. Of the 47 recipients who started college, 27 are currently enrolled, 11 graduated, and nine did not finish college. Ninety-four patients have health insurance, 40 are employed, and 31 receive financial assistance for a disability. The majority of recipients of pediatric heart transplantation are able to reach reasonable academic milestones, achieve social well-being, and professional independence. [ABSTRACT FROM AUTHOR]

This review details the indications for heart transplantation in children. Contraindications have evolved from absolute to relative. Controversial issues remain and this paper represents a consensus of more than a dozen centers that have programs that remain active performing pediatric heart transplants. [ABSTRACT FROM AUTHOR]

Background: Few data describe exercise performance after cardiac transplantation during infancy. The aim of this study was to compare the cardiorespiratory response to exercise in healthy subjects with that of subjects who had undergone heart transplantation during infancy to treat hypoplastic left heart syndrome.Methods: Subjects (24 heart transplant recipients and 25 healthy controls) exercised on a treadmill using pediatric ramp protocols. We measured heart rate (HR), blood pressure, and metabolic data. Median age at transplantation was 20 days (range, 4 to 97 days). Age of recipients at exercise testing was 9.7 ± 2.3 years and in healthy subjects was 10.5 ± 1.4 years (p = not significant [NS]).Results: Exercise duration was similar in both groups (10.3 ± 2.0 minutes in recipients vs 11.1 ± 1.5 minutes in healthy subjects, (p = NS). Heart rate at rest was greater in recipients (94 ± 15 beats per minute [bpm] vs 85 ± 11 bpm, p = 0.02). Peak HR also was less in the recipient group (158 ± 15 bpm vs 189 ± 12 bpm, p < 0.001). Peak oxygen consumption was 14% less in the recipients (32.3 ± 5.6 ml/kg/min vs 36.8 ± 5.5 ml/kg/min, p < 0.01). Ventilatory anaerobic threshold was decreased in recipients, 27.6 ± 9.6 vs 32.8 ± 6.0, p < 0.05. Respiratory exchange ratio at peak exercise was equal in both groups (1.06 ± 0.06 vs 1.06 ± 0.08). Oxygen pulse index did not differ significantly, 5.5 ± 1.1 ml/beat/m2 in recipients and 6.1 ± 1.7 ml/beat/m2 in healthy subjects (p = NS).Conclusions: Overall, children who undergo cardiac transplantation in infancy have exercise capacities within the normal range. These recipients have a decreased heart rate reserve that may account for the differences in peak oxygen consumption when compared with healthy subjects. [Copyright &y& Elsevier]

Background: There are few published data regarding the long-term outcome of “large” cardiac allografts in children. This study examines the effect of cardiac graft oversizing on the survival of pediatric patients with congenital heart disease (CHD).Methods: Two hundred ninety-one children, age 1 day to 17 years (median 50 days), with CHD underwent primary cardiac transplantation between 1985 and 2002. Patients were analyzed according to donor-recipient weight ratio (D-R): Group (Gp) I (n = 252) with D-R <2.5 (range 0.59 to 2.49, median 1.4), and Gp II (n = 39) with D-R ≥2.5 (range 2.5 to 4.65, median 2.78). CHD diagnoses included hypoplastic left heart syndrome (138 in Gp I, 13 in Gp II), single ventricle (29 in Gp I, 1 in Gp II) and other (85 in Gp I, 13 in Gp II). Patients with cardiomyopathy were excluded. Pre-transplant cardiac palliation was performed in 36% of Gp I and 15% of Gp II patients. The average graft ischemic times (minutes) were 266 ± 7.5 and 283 ± 18.9 for Gp I and Gp II, respectively (p < 0.2).Results: The operative mortality for Gp I was 10.3% and 10.2% for Gp II (p < 0.99). There was no significant difference between the 2 groups in length of hospital stay (p < 0.15) or duration of ventilator support (p < 0.6) post-transplantation. However, the incidence of open chest was higher (p < 0.003) in Gp II (28%) compared with Gp I (8%). The survival rates for Gp I and Gp II were: 82 ± 2.4% vs 84 ± 5.7% at 1 year; 71 ± 2.9% vs 72 ± 7.2% at 5 years; and 63 ± 3.2% vs 65% ± 7.4 at 10 years.Conclusions: Post-transplant morbidity and short- and long-term survival of pediatric recipients with CHD are not adversely influenced by the use of oversized cardiac allografts. [Copyright &y& Elsevier]

Surgical mortality is high in children with visceral heterotaxy (VH), particularly if atrioventricular valve insufficiency, ventricular dysfunction, or aortic atresia is present. This study reviews the outcome of cardiac transplantation (CT) in infants and children with VH and congenital heart disease who are at high risk for standard palliative or corrective surgery. We reviewed CT outcomes in 29 children with VH, congenital heart disease, atrioventricular valve insufficiency, ventricular dysfunction, and/or aortic atresia. Median age at CT was 3.1 years. Cardiac surgery had been performed in 20 patients (69%) before CT. Follow-up since CT has been 8.5 ± 2.2 years. Outcomes were compared with 45 children who underwent transplantation for dilated cardiomyopathy. Actuarial graft survival in the VH group at 30 days and 1, 5, and 10 years was 100%, 86%, 68%, and 50%, respectively, compared with 100%, 96%, 83%, and 68% in children who underwent transplantation for dilated cardiomyopathy (p = 0.12). Splenic status, cardiac position, age at CT, number of prior cardiac surgeries, or systemic venous anomalies were not predictors of mortality after CT. Cardiopulmonary bypass and graft ischemic times were longer in the VH group; time on the ventilator after CT, length of hospitalization, and rejection, infection, post-transplant lymphoproliferative disease, and transplant coronary artery disease rates were equal. Thus, CT is a viable alternative therapy for high-risk patients with VH, possibly offering improved survival over standard surgical management. [Copyright &y& Elsevier]