Heart Transplantation In Children Research Articles

Outcomes of heart transplantation in children with heterotaxy syndrome.

End-stage congenital heart disease in children with heterotaxy syndrome might necessitate heart transplantation. Heart transplantation in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction), and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. We aim to examine if heterotaxy syndrome is associated with increased early or late transplantation risks. The United Network for Organ Sharing transplantation database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received heart transplantation. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. After merger, our cohort of 1122 patients was divided to three groups: group heterotaxy (n = 143), group non-heterotaxy congenital (n = 428) and group cardiomyopathy (n = 551). There were differences in the characteristics between the 3 groups, with heterotaxy being comparable to non-heterotaxy congenital group. The waitlist duration was longer for heterotaxy than non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, p < 0.001). Early post-transplant complications were similar for all groups except for operative mortality that was 1% for cardiomyopathy and 4% for heterotaxy and non-heterotaxy congenital, p < 0.001. Post-transplant stay was shorter for cardiomyopathy (57) compared to non-heterotaxy congenital (99) and heterotaxy (89) days, p < 0.001. While rejection prior to discharge was comparable between heterotaxy and CHD groups, it was higher at 1-year for heterotaxy (22%), than non-heterotaxy congenital (19%) and cardiomyopathy (13%), p < 0.001. Survival at 5 years was superior for cardiomyopathy (87%) compared to heterotaxy (69%) and non-heterotaxy congenital (78%), p < 0.001. For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. Despite complexity, heart transplantation in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to other patients with congenital heart disease, the increasing rejection rate at one year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomic and surgical variables that could affect survival.

NT-proBNP for Predicting All-Cause Death and Heart Transplant in Children and Adults with Heart Failure.

Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) concentration is a heart failure (HF) biomarker in adults and children. Its prognostic value for HF-related events has been established only in adults. Therefore, weaimed to test the hypothesis that plasma NT-proBNP concentrations predicted the risk of heart transplantation or death in children with HF. We studied the medical records of 109 children with HF enrolled in the IBM Watson Explorys database and from 150 children enrolled in the Pediatric Cardiomyopathy Registry (PCMR). Nonlinear regression was used to assess the relationship between plasma NT-proBNP concentrations and the risk of events in the two cohorts. All children in the PCMR cohort had dilated cardiomyopathy. The Explorys cohort also included children with congenital cardiovascular malformations. Median plasma NT-proBNP concentrations were 1250pg/mL and 184pg/mL in the Explorys and PCMR cohorts, respectively. The percentage of deaths/heart transplantations was 7%/22%, over 2years in the Explorys cohort and 3%/16% over 5years in the PCMR cohort. Mean estimates of plasma NT-proBNP concentration indicative of half-maximum relative risk for events (EC50 values) at 2 and 5years were 3730pg/mL and 4199pg/mL, respectively, values both close to the mean of 3880pg/mL established for adults with HF. The plasma NT-proBNP concentration is suitable for estimating relative risk of mortality and heart transplantation in children with HF, independent of etiology and shows similar relations to clinical outcomes as in adults, indicating its likely value as a surrogate marker both for adult and pediatric HF.ClinicalTrials.gov Identifiers: NCT00005391 (May 26, 2000), NCT01873976 (June 10, 2013).

(1247) - A Single Institutional Experience of Heart Transplantation in Children with Functional Single Ventricle

(1247) - A Single Institutional Experience of Heart Transplantation in Children with Functional Single Ventricle

Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. This study provides data on anticipated renal trajectory following retransplantation.

Long term results of pediatric heart transplantations - single center experiences.

Heart failure (HF) is characterized by significant mortality in both adults and children. Characteristic of paediatric HF are feeding problems, poor weight gain, exercise intolerance or dyspnoea. These changes are often accompanied by endocrine disorders. The main causes of HF are congenital heart defects (CHD) cardiomyopathies, arrhythmias, myocarditis or heart failure secondary to oncological treatment. Heart transplantation (HTx) is the method of choice for treatment of end-stage HF in paediatric patients. The aim is to summarize single center experience in heart transplantation in children. Between 1988 and 2021 in the Silesian Center for Heart Diseases in Zabrze 122 pediatric cardiac transplantations were performed. In the group of recipients with falling Fontan circulation HTx was performed in 5 children. The study group was evaluated for postoperative course: rejection episodes depending on the medical treatment scheme, coinfections and mortality. 1-, 5- and 10-year survival rate between 1988 and 2001 were 53%, 53% and 50%, respectively. 1-, 5- and 10-year survival rate between 2002 and 2011 was 97%, 90% and 87%; between 2012 and 2021 1-year observation with survival rate 92%. The main cause of mortality both in early and in late period after transplantation was graft failure. Cardiac transplantation in children remains the main method of treatment of end-stage heart failure. Our results at both early and long-term posttransplant period, are comparable to those obtained in the most experienced foreign centers.

The Role of Multimodality Imaging in Pediatric Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.

Heart Transplantation in Children and Adults With Congenital Heart Disease: 3 Decades of Evolution

Heart transplantation is the treatment of choice for children and adults with congenital heart disease. We report the heart transplant single-center experience. The number of transplantations has increased over the last 3 decades. The Kaplan-Meier survival curves in the first, second, and third decades at 5 and 10 years were 69% and 59%, 62% and 52%, and 66% and 60%, respectively.

Out‐of‐pocket expenses associated with pediatric heart transplantation

Heart transplantation in children is associated with high resource utilization. However, the financial burden on families and the association with patient and demographic factors remains unclear. This study aims to examine out-of-pocket expenses associated with pediatric heart transplantation. An anonymous REDCap survey was distributed to caregivers of children who have undergone heart transplantation using social media, national organizations, and during clinic encounters from May through August 2022. There were a total of 146 respondents. The median monthly out-of-pocket expense was $250 (IQR $75-$500) and 20 respondents (13.7%) reported monthly expenses of >$1000. Families with commercial insurance reported significantly higher out-of-pocket expenses compared to those with government-sponsored insurance (median $350 vs. $100, p < .001). Families with government-sponsored insurance were most happy with their insurance coverage, followed by commercial insurance and then coverage through the Affordable Care Act (p < .001 for all pairwise comparisons). There was no statistically significant difference in overall transplant-related out-of-pocket expenses based on total household income (p = .222). Monthly out-of-pocket expense was not associated with the number of medications, type of immunosuppressants, or post-transplant complications including rejection, PTLD, or CAV (p = NS for all). Cardiac catheterizations and unplanned admissions were reported as the events that incurred the highest out-of-pocket expense. Families of children who have undergone heart transplantation can incur significant out-of-pocket expenses and strategies to mitigate this financial burden should be investigated.

(601) Outcomes of Heart Transplantation in Children with Familial Dilated Cardiomyopathy

(601) Outcomes of Heart Transplantation in Children with Familial Dilated Cardiomyopathy

(82) Outcomes of Heart Transplantation in Children with Previously Palliated Hypoplastic Left Heart Syndrome

(82) Outcomes of Heart Transplantation in Children with Previously Palliated Hypoplastic Left Heart Syndrome

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Contemporary Outcomes of Heart Transplantation in Children with Heterotaxy Syndrome: Sub-Optimal Pre-Transplant Optimization Translates into Early Post-Transplant Mortality.

Patients with heterotaxy syndrome and congenital heart disease (CHD) experience inferior cardiac surgical outcomes. Heart transplantation outcomes are understudied, however, particularly compared to non-CHD patients. Data from UNOS and PHIS were used to identify 4803 children (< 18years) undergoing first-time heart transplant between 2003 and 2022 with diagnoses of heterotaxy (n = 278), other-CHD (n = 2236), and non-CHD cardiomyopathy (n = 2289). Heterotaxy patients were older (median 5yr) and heavier (median 17kg) at transplant than other-CHD (median 2yr and 12kg), and younger and lighter than cardiomyopathy (median 7yr and 24kg) (all p < 0.001). UNOS status 1A/1 at listing was not different between groups (65-67%; p = 0.683). At transplant, heterotaxy and other-CHD patients had similar rates of renal dysfunction (12 and 17%), inotropes (10% and 11%), and ventilator-dependence (19 and 18%). Compared to cardiomyopathy, heterotaxy patients had comparable renal dysfunction (9%, p = 0.058) and inotropes (46%, p = 0.097) but more hepatic dysfunction (17%, p < 0.001) and ventilator-dependence (12%, p = 0.003). Rates of ventricular assist device (VAD) were: heterotaxy-10%, other-CHD-11% (p = 0.839 vs. heterotaxy), cardiomyopathy-37% (p < 0.001 vs. heterotaxy). The 1-year incidence of acute rejection post-transplant was comparable between heterotaxy and others (p > 0.05). While overall post-transplant survival was significantly worse for heterotaxy than others (p < 0.05 vs. both), conditional 1-year survival was comparable (p > 0.3 vs. both). Children with heterotaxy syndrome experience inferior post-heart transplant survival, although early mortality appears to influence this trend, with 1-year survivors having equivalent outcomes. Given similar pre-transplant clinical status to others, heterotaxy patients are potentially under risk-stratified. Increased VAD utilization and pre-transplant end-organ function optimization may portend improved outcomes.

Primary cardiomyopathies in childhood: clinical and diagnostic features (literature review)

Primary cardiomyopathies in childhood are a rare but serious disease that is a common cause of heart failure and the most common reason for heart transplantation in children over one year of age. Over the past decades, the diagnosis of cardiomyopathy has advanced from traditional clinical imaging methods to new genetic and imaging techniques. The article presents a review of the literature data on the modern classification of primary pediatric cardiomyopathies and the features of the clinical course and imaging, which is an integral part of the diagnosis based on the primary morphofunctional phenotype.

Partial heart transplantation can ameliorate donor organ utilization.

The treatment of babies with unrepairable heart valve dysfunction remains an unsolved problem because there are no growing heart valve implants. However, orthotopic heart transplants are known to grow with recipients. Partial heart transplantation is a new approach to delivering growing heart valve implants, which involves transplantation of the part of the heart containing the valves only. In this review, we discuss the benefits of this procedure in children with unrepairable valve dysfunction. Partial heart transplantation can be performed using donor hearts with poor ventricular function and slow progression to donation after cardiac death. This should ameliorate donor heart utilization and avoid both primary orthotopic heart transplantation in children with unrepairable heart valve dysfunction and progression of these children to end-stage heart failure.

Heart transplantation in children and adults with Down syndrome: A single centre experience.

In recent years, rapid advances in cardiac surgery and changes in attitude towards patients with cognitive disability have led to these patients receiving cardiac transplantation. This is a retrospective report describing the experience of four patients with Down Syndrome who received heart transplantation in a single institution. Anthracycline-induced cardiomyopathy was the most common cause of heart failure in this group (3/4). Two patients were bridged to transplantation, one by using a combination of extra-corporeal membrane oxygenation and biventricular assist device and the other by using a durable implantable left ventricular assist device. All the four patients are alive with the longest surviving patient 17 years after transplantation. Against strong hypothetical predictions, we observed no propensity for the development of post-transplant infections or lymphoproliferative disorders. Down Syndrome should not be the sole contraindication to heart transplantation. The decision for transplantation should be on a case-by-case basis provided adequate social support is in place.

The importance of mechanical circulatory support on pediatric waitlist and post heart transplant survival: a narrative review

Background and Objective: While heart transplantation for children with end-stage heart failure has been available for more than 50 years, outcomes on the waitlist and as well as post-transplant outcomes have not always been favorable. Post-transplant survival initially showed marked improvement with better and better immunosuppression regimens. However, waitlist outcomes (as well as those deemed too sick to list) remained unfortunately low. With the introduction of mechanical circulatory support (MCS) in the 1970s, a new hope for the those with end-stage heart failure emerged. This paper will review the past, present and what is on the horizon for MCS as a bridge to heart transplantation in pediatric patients.

Multimodality Imaging to Detect Rejection, and Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients—An Illustrative Review

The three most common modalities of graft surveillance in pediatric heart transplant (HT) recipients include echocardiography, coronary angiography, and endomyocardial biopsy (EMB). The survival outcomes after HT in children have improved considerably in recent years. However, allograft rejection and cardiac allograft vasculopathy remain the leading cause of death or re-transplantation. The routine surveillance by EMB and coronary angiography are invasive and risky. Newer noninvasive echocardiographic techniques, including tissue Doppler imaging (TDI), 2-D speckle tracking echocardiography, CT coronary angiography (CTCA), cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) and invasive techniques such as intravascular ultrasound (IVUS), functional flow reserve (CFR) of coronary arteries, optical coherence tomography (OCT), have emerged as powerful tools which may help early recognition of sub-clinical rejection, response to treatment, early detection, and progression of CAV. The multimodality imaging approach, including noninvasive and invasive tests, is the future for the transplanted heart to detect dysfunction, rejections, and early CAV. This review illustrates noninvasive and invasive imaging techniques currently used or could be considered for clinical use in detecting heart transplant rejection, dysfunction, and CAV in children.

Immunological differences between heart- and kidney-transplanted children: a cross-sectional study.

Post-transplantation lymphoproliferative disorder is a potentially mortal complication after heart transplantation in children. As the immune system plays a crucial role in the development of lymphoma, we explored the influence of thymus function in relation to immunosuppressive treatment in organ-transplanted children and healthy control subjects. A prospective case-control study was performed at a single centre, in which 36 children who had undergone heart transplantation were compared to two control groups: 34 kidney-transplanted children and 33 healthy age- and sex-matched children. T- and B-lymphocyte subtypes and monocytes were analysed by flow cytometry, and T-cell receptor excision circles were assessed using quantitative polymerase chain reaction. Heart-transplanted children had a lymphocyte profile characterised by reduced or absent thymic function with low numbers of T-cell receptor excision circles and total and naïve T cells, together with immune activation against the allograft. Despite similar immunosuppressive treatment, the kidney-transplanted group showed an activated T-lymphocyte compartment.

‘A new normal’? Ventricular Assist Device implantation and subsequent heart transplant in children and adolescents: A family experience

Ventricular Assist Devices (VAD) are enabling children experiencing severe heart failure, who would have otherwise died, to be bridged to transplant or recovery. Donated Paediatric hearts are in short supply, so the use of VAD is likely to continue to support paediatric patients for the foreseeable future. This study explored the experiences of children and young people (CYP) being supported by VAD and their families. Semi-structured interviews were undertaken with 24 families after transplant (either parents only, parents and CYP together, or CYP only), and two participant observations with families currently living with a child on VAD. This study was conducted at one of two UK Paediatric Heart Transplantation Centres. The data suggest that families adjust to a ‘new normal’ that the heart failure and subsequent medical intervention brings. This involves adjusting to the initial diagnosis and need for VAD implantation; establishing a new life on VAD; the emotional roller coaster that comes with this highly invasive treatment option; and, adapting to a new way of life following transplant. This research adds to the limited available research on the experience of families with a CYP being supported by VAD. The family viewpoint raises important issues about highly invasive treatment, the lived realities of VAD implantation and subsequent transplant, and the forever changed lives post discharge. These perspectives are of great importance when considering the growth of both VAD implantation and paediatric heart transplantations as established therapeutic treatment options.

A Systematic Review Incorporating Meta-Analysis on the Effectiveness of Intravenous Immunoglobulin Versus Corticosteroids in the Treatment of Pediatric Myocarditis

Background: Concerns have been raised about the efficacy of intravenous immunoglobulin and corticosteroids in pediatric myocarditis; however, the relationship between the risk and efficacy of these two therapies in children with myocarditis varies. Methods: A systematic review on seventeen studies was conducted in July 2020, which included 1,960 subjects at the baseline, with 788 receiving intravenous immunoglobulin and 142 receiving corticosteroids. The mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the prognostic role of both treatments using dichotomous and continuous methods with random or fixed-effect models. Results: The use of intravenous immunoglobulin was significantly associated with a lower mortality rate or heart transplantation in children with myocarditis (OR, 0.55; 95% CI, 0.40-0.77, p &lt; 0.001) compared with the control group. However, corticosteroids were not significantly associated with the same parameters (OR, 0.72; 95% CI, 0.31-1.63, p = 0.43). The use of intravenous immunoglobulin was not significantly related to improving left ventricular ejection in children with myocarditis (OR, 2.30; 95% CI, -9.65-14.25, p = 0.71) and so were corticosteroids (MD, 5.17; 95% CI, -0.26-10.60, p = 0.06). Conclusion: The use of intravenous immunoglobulin might have an independent risk relationship with a lower mortality rate or heart transplantation and is recommended in children with myocarditis to prevent complications.