Current Cardiology Reviews - Volume 7, Issue 2, 2011

Orthotopic heart transplantation has been performed in pediatric patients for 27 years. Indications changed through the years, showing the increase of patients receiving a heart transplant for congenital heart defects, after having experienced repeated surgical palliations. At present, 1-year survival > 65% can be expected following pediatric heart transplantation. Morbidity other than hypertension is uncommon and catch-up growth and hemodynamic rehabilitation to normal childhood functional status is the likely outcome. The quality of life can be normal. The diagnosis of CHD is a risk factor for mortality in OHT recipients based on the ISHLT data. For mortality within one year from transplant, the relative risk for pediatric OHT patients with CHD is 2.17 for pediatric OHT recipients older than one year. For 5-year mortality, the hazard ratio for CHD patients vs. others has been reported as 1.50. With regards to long term survival data, the ISHLT data reveal improvements over time for all pediatric OHT recipients. An important factor for success in CHD patients is careful patient evaluation prior to OHT. Guidelines have been developed to assist in the assessment of the risk profile of this very heterogeneous patient group. Broadly, both biological and psycho-social factors have to be taken into consideration. Heart transplantation remains the only hope for children with some forms of complex congenital heart disease and some infants and children with failed surgical intervention. In specific cases, OHT may offer a better likelihood of long terms survival than conventional medical and surgical therapy although the shortage of donor organs limits the feasibility of the primary OHT approach. Progress in immunology has enhanced the success rate of long term management of graft rejection. The overall survival after OHT for congenital heart disease has improved compared to all other indications. There is an increasing body of experience with the specific challenges of OHT for congenital heart disease, both as primary treatment option or as rescue after other therapies have failed. These indications to transplant for congenital heart defects, the selection criteria of patients, the related risks and possible complications are still not well defined. For this reason, we propose a text which deals with both the problems of patients suffering from congenital heart disease who are referred to heart transplant programs and the possible future prospects. The review discusses the indications for heart transplantation, various phases of the transplant process, the immunosuppressive treatment and the role of heart transplant in the group of congenital patients.

In this review we have looked at indications for cardiac transplantation in congenital heart disease. An outline of the general principles of the use of transplant as a management strategy both as a first line treatment and following other surgical interventions is discussed. We explore the importance of the timing of patient referral and the evaluations undertaken, and how the results of these may vary between patients with congenital heart disease and patients with other causes of end-stage heart failure. The potential complications associated with patients with congenital heart disease need to be both anticipated and managed appropriately by an experienced team. Timing of transplantation in congenital heart disease is difficult to standardize as the group of patients is heterogeneous. We discuss the role and limitations of investigations such as BNP, 6 minute walk, metabolic exercise testing and self estimated physical functioning. We also discuss the suitability for listing. It is clear that congenital heart patients should not be considered to be at uniform high risk of death at transplant. Morbidity varies greatly in the congenital patient population with the failing Fontan circulation having a far higher risk than a failing Mustard circulation. However the underlying issue of imbalance between donor organ supply and demand needs to be addressed as transplant teams are finding themselves in the increasingly difficult situation of supporting growing numbers of patients with a diverse range of pathologies with declining numbers of donor organs.

Congenital heart disease is one of the major diagnoses in pediatric heart transplantation recipients of all age groups. Assessment of pulmonary vascular resistance in these patients prior to transplantation is crucial to determine their candidacy, however, it is frequently inaccurate because of their abnormal anatomy and physiology. This problem places them at significant risk for pulmonary hypertension and right ventricular failure post transplantation. The pathophysiology of pulmonary vascular disease in children with congenital heart disease depends on their pulmonary blood flow patterns, systemic ventricle function, as well as semilunar valves and atrioventricular valves structure and function. In our review we analyze the pathophysiology of pulmonary vascular disease in children with congenital heart disease and end-stage heart failure, and outline the state of the art pre-transplantation medical and surgical management to achieve reverse remodeling of the pulmonary vasculature by using pulmonary vasodilators and mechanical circulatory support.

Children and adults with congenital heart disease (CHD) can require interventions that result in immunologic alterations that are different than those seen in patients with cardiomyopathies. Patients with CHD can be exposed to heart surgeries, blood products, valved and non-valved allograft tissue, and mechanical circulatory support, all of which can alter the immunologic status of these patients. This change in immunologic status is most commonly manifested as the development of anti-human leukocyte antigen (HLA) antibodies. This review will delineate a) the causes of anti-HLA antibody production (often referred to as allosensitization); b) preventive strategies for anti-HLA antibody production before transplantation; c) treatment strategies for those patients who develop anti-HLA antibodies before transplantation; d) consequences of HLA allosensitization after transplantation; and e) treatment of HLA allosensitization and antibody-mediated rejection after transplantation.

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%. Posttransplant 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.

Parallel advancements in surgical technique, preoperative and postoperative care, as well as a better understanding of physiology in patients with duct-dependent pulmonary or systemic circulation and a functional single ventricle, have led to superb results in staged palliation of most complex congenital heart disease (CHD) [1]. The Fontan procedure and its technical modifications have resulted in markedly improved outcomes of patients with single ventricle anatomy [2,3,4]. The improved early survival has led to an exponential increase of the proportion of Fontan patients surviving long into adolescence and young adulthood [5]. Improved early and late survival has not yet abolished late mortality secondary to myocardial failure, therefore increasing the referrals for cardiac transplantation [6]. Interstage attrition [7] is moreover expected in staged palliation towards completion of a Fontan-type circulation, while Fontan failure represents a growing indication for heart transplantation [8]. Heart transplantation has therefore become the potential “fourth stage” [9] or a possible alternative to a high-risk Fontan operation [10] in a strategy of staged palliation for single ventricle physiology. Heart transplant barely accounts for 16% of pediatric solid organ transplants [11]. The thirteenth official pediatric heart transplantation report- 2010 [11] indicates that pediatric recipients received only 12.5% of the total reported heart transplants worldwide. Congenital heart disease is not only the most common recipient diagnosis, but also the most powerful predictor of 1-year mortality after OHT. Results of orthotopic heart transplantations (OHT) for failing single ventricle physiology are mixed. Some authors advocate excellent early and mid-term survival after OHT for failing Fontan [9], while others suggest that rescue-OHT after failing Fontan seems unwarranted [10]. Moreover, OHT outcome appears to be different according to the surgical staging towards the Fontan operation and surgical technique of Fontan completion [12]. The focus of this report is a complete review of the recent literature on OHT for failing single ventricles, outlining the clinical issues affecting Fontan failure, OHT listing and OHT outcome. These data are endorsed reporting our experience with OHT for failing single ventricle physiology in recent years.

Heart transplantation is an accepted therapeutic modality for end-stage congenital heart disease for both biventricular and univentricular anomalies. Many transplant centers have pushed the limits of transplantation to include patients with high pulmonary vascular resistance, high panel reactive antibodies, positive cross-matches, and ABOincompatibility. Excellent results have been possible, particularly with the development of improved diagnostic and therapeutic algorithms to prevent and treat rejection, infection, and post-transplant lymphoproliferative disease. Late graft failure and chronic rejection remain vexing problems. The vast majority of patients with biventricular congenital heart disease have undergone prior cardiac surgical procedures. Indications for transplantation in this subgroup are primarily progressive refractory heart failure following prior cardiac surgical reconstructive procedures. Contraindications to transplantation mimic those for other forms of end-stage heart disease. A determination of pulmonary vascular resistance is important in listing patients with biventricular congenital heart disease for heart transplantation. Modifications in the implant technique are necessary and vary depending on underlying recipient anatomy. Risk factors for perioperative outcomes in patients with biventricular congenital heart disease include the need for reoperation, the degree of anatomic reconstruction necessary during the implant procedure, and the degree of antibody sensitization, in addition to a number of other recipient and donor factors. Postoperative outcomes and survival are very good but remain inferior to those with cardiomyopathy in most series. In conclusion, patients with end-stage biventricular congenital heart disease represent a complex group of patients for heart transplantation, and require careful evaluation and management to ensure optimal outcomes.

Approximately one in one hundred children is born with congenital heart disease. Most can be managed with corrective or palliative surgery but a small group will develop severe heart failure, leaving cardiac transplantation as the ultimate treatment option. Unfortunately, due to the inadequate number of available donor organs, only a small number of patients can benefit from this therapy, and mortality remains high for pediatric patients awaiting heart transplantation, especially compared to adults. The purpose of this review is to describe the potential role of mechanical circulatory support in this context and to review current experience. For patients with congenital heart disease, ventricular assist devices are most commonly used as a bridge to cardiac transplantation, an application which has been shown to have several important advantages over medical therapy alone or support with extracorporeal membrane oxygenation, including improved survival to transplant, less exposure to blood products with less immune sensitization, and improved organ function. While these devices may improve wait list mortality, the chronic shortage of donor organs for children is likely to remain a problem into the foreseeable future. Therefore, there is great interest in the development of mechanical ventricular assist devices as potential destination therapy for congenital heart disease patients with end-stage heart failure. This review first discusses the experience with the currently available ventricular assist devices in children with congenital heart disease, and then follows to discuss what devices are under development and may reach the bedside soon.

The successful delivery of optimal peri-operative care to pediatric heart transplant recipients is a vital determinant of their overall outcomes. The practitioner caring for these patients must be familiar with and treat multiple simultaneous issues in a patient who may have been critically ill preoperatively. In addition to the complexities involved in treating any child following cardiac surgery, caretakers of newly transplanted patients encounter multiple transplant-specific issues. This chapter details peri-operative management strategies, frequently encountered early morbidities, initiation of immunosuppression including induction, and short-term outcomes.

Background & Objectives: As more heart transplant recipients survive into late adolescence, research addressing long-term psychosocial and neurodevelopmental outcomes is imperative. The limited literature available suggests risk for psychosocial difficulties and lower cognitive, academic, and neuropsychological functioning. This paper reviews topic-related literature and provides preliminary data examining psychosocial and neuropsychological functioning of adolescents who received their heart transplant during infancy. Method: This paper offers a literature review AND presents preliminary data from studies conducted through Loma Linda University Children's Hospital (LLUCH). Study one examined psychosocial functioning and quality of life of adolescent infant heart transplant recipients. In study two, cognitive, academic, and neuropsychological data were analyzed. Results: Study 1: Overall psychosocial functioning fell in the Average range, however, a significant percentage of participants presented with difficulties on one or more of the psychosocial domains. Quality of life was also within normal limits, though concerns with general health and bodily discomfort were noted. Study 2: Cognitive functioning was assessed to be Below Average, with 43-62% of the participants demonstrating significant impairments. Neuropsychological functioning yielded significant weakness on language functioning, and mild weakness on visual-motor integration and executive functioning. Conclusion: While the majority of the participants demonstrate psychosocial resiliency, a subgroup present with difficulties suggesting the need for intervention. Cognitive/neuropsychological functioning suggests poorer functioning with patterns similar to other high-risk pediatric populations. These results are preliminary and further research on long-term psychosocial and neuropsychological development of pediatric heart transplant recipients is needed to better understand and ameliorate developmental trajectories.