Risk factors for 1-year allograft loss in pediatric heart transplant patients using machine learning: An analysis of the pediatric heart transplant society database.

BACKGROUND: Pediatric heart transplant patients are at greatest risk of allograft loss in the first year. We assessed whether machine learning could improve 1-year risk assessment using the Pediatric Heart Transplant Society database. METHODS: Patients transplanted from 2010 to 2019 were included. The primary outcome was 1-year graft loss free survival. We developed a prediction model using cross-validation, by comparing Cox regression, gradient boosting, and random forests. The modeling strategy with the best discrimination and calibration was applied to fit a final prediction model. We used Shapley additive explanation (SHAP) values to perform variable selection and to estimate effect sizes and importance of individual variables when interpreting the final prediction model. RESULTS: Cumulative incidence of graft loss or mortality was 7.6%. Random forests had favorable discrimination and calibration compared to Cox proportional hazards with a C-statistic (95% confidence interval [CI]) of 0.74 (0.72, 0.76) versus 0.71 (0.69, 0.73), and closer alignment between predicted and observed risk. SHAP values computed using the final prediction model indicated that the diagnosis of congenital heart disease (CHD) increased 1 year predicted risk of graft loss by 1.7 (i.e., from 7.6% to 9.3%), need for mechanical circulatory support increased predicted risk by 2, and single ventricle CHD increased predicted risk by 1.9. These three predictors, respectively, were also estimated to be the most important among the 15 predictors in the final model. CONCLUSIONS: Risk prediction models used to facilitate patient selection for pediatric heart transplant can be improved without loss of interpretability using machine learning.

COVID-19 diagnosis and testing in pediatric heart transplant recipients.

Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of infection, COVID-19 is well tolerated in this population (5% admission from home; 0% mortality). A suppressed immune system does not significantly inhibit an antibody response in pediatric heart transplant recipients (>70% antibody seroconversion) and appears to persist, similar to those without transplantation (>90 days). Routine testing for COVID-19 via PCR and antibody testing enhances the ability to detect COVID-19 infection in asymptomatic patients and may help reduce unintended transmission to more susceptible individuals.

Utility of preprocedure checklists in the congenital cardiac catheterization laboratory.

OBJECTIVE: Preprocedure meetings have become more commonplace in medicine but are not performed routinely in the cardiac catheterization laboratory. We sought to create, implement, and evaluate a preprocedural meeting in the form of a checklist for the cardiac catheterization laboratory. Staff attitudes and perceptions toward safety and sense of teamwork were also analyzed. DESIGN: All procedures performed in the cardiac catheterization laboratory on patients with structural heart disease from January 2010 to February 2012 were retrospectively reviewed for demographics, procedural details, and reported complications. A checklist was introduced to the preprocedure protocol at the halfway point, and patients were divided into pre- and postchecklist cohorts. Anesthesia and cardiac catheterization laboratory staff were surveyed at the beginning and end of the study period regarding attitude toward safety, team climate, and the impact of errors. RESULTS: Total number of procedures (prechecklist, n = 371; postchecklist, n = 370) and demographics were similar among groups. Complication rates were equivalent pre- and postchecklist, but there was a greater proportion of interventional cases and higher median complication level in the postchecklist group. Cardiac catheterization laboratory staff reported improved awareness of being briefed with the checklist. Anesthesia differed from cardiac catheterization staff in perception of communication as well as team and safety climate. CONCLUSIONS: A preprocedure checklist for congenital cardiac catheterization cases is easy to perform and serves to update cardiac catheterization laboratory staff. Anesthesia and cardiac catheterization staff had different perceptions of safety and teamwork climate. Further studies are needed to determine if this briefing could lead to better communication among services and ultimately reduce complications.

Occlusion of Sano conduit with the Amplatzer vascular plug: a reliable method for staged elimination of accessory pulmonary blood flow in single ventricle palliation.

BACKGROUND: Staged palliative surgery is often required to regulate pulmonary and systemic blood flow in children with complex congenital heart disease. Accessory sources of pulmonary blood flow have been utilized to provide satisfactory pulmonary blood flow after Glenn anastomosis in select patients. Prolonged exposure to increased flow can lead to elevated pulmonary arterial pressures and volume loading of the ventricle, potentially limiting candidacy for Fontan completion. OBJECTIVE: To review the feasibility, technique, and outcome of transcatheter closure of the Sano conduit utilizing the Amplatzer Vascular Plug (AVP). METHODS: All patients who underwent device closure of the Sano conduit with an AVP were reviewed retrospectively. Patient demographics, indications, procedural details, and patient outcomes were reviewed. Hemodynamic changes before and after occlusion of the Sano conduit were compared. A P value < 0.05 was considered significant. RESULTS: Between 2005 and 2009, 11 male patients underwent Sano occlusion with an AVP. Average weight was 8.8 ± 2.2 kg. The Sano was occluded from both antegrade (n = 6) and retrograde (n = 5) approaches. Arterial saturation and mean pulmonary artery pressure both decreased significantly after Sano occlusion [86.9 ± 4.9% to 82.6 ± 4.9% (P < 0.001) and 14.1 ± 5 mm Hg to 12.8 ± 4 mm Hg (P < 0.05), respectively]. Conduit diameter averaged 3.6 mm (range 3.1-4.4) 13 months after Stage I palliation. The conduit was closed using a 6 mm AVP in nine patients and a 4 mm AVP in the other two. The ratio of AVP size to conduit diameter was 1.5 ± 0.27. There were no procedural complications and all patients at least 2 years of age have undergone Fontan completion. CONCLUSIONS: The Sano conduit can be left open in select patients who do not tolerate closure after Glenn anastomosis. It can be closed safely and effectively using the AVP. © 2010 Wiley-Liss, Inc.

Cardiac allograft vasculopathy in pediatric heart transplant recipients.

Metabolic parameters for coronary allograft vasculopathy (CAV) have not been well defined in children. CAV (by angiography or autopsy) was studied in 337 heart recipients on a cyclosporine-based steroid-sparing regimen. Freedom from CAV for all was 79% at 10 years. Fifty-nine patients (18%) developed CAV at a mean of 6.5 +/- 3 years post-transplant. First year rejections were significantly higher in CAV, mean 2.3 vs. 1.4, P = 0.003, odds ratio (OR) 1.8. Rejection with hemodynamic compromise beyond 1 year post-transplant was associated with CAV, P < 0.001, OR 8.4. There was no significant correlation among human leukocyte antigen DR (HLA DR) mismatch, pacemaker use or homocysteine levels and the development of CAV. Maximum cholesterol and low density lipoprotein (LDL) levels were not significantly different. Neither diabetes nor hypertension was significant predictors of CAV on multivariate logistic regression analysis. In conclusion, frequent and severe rejection episodes may predict pediatric CAV. Neither glucose intolerance nor lipid abnormalities appeared to alter risk for CAV in this population.

The impact and outcome of transplant coronary artery disease in a pediatric population: a 9-year multi-institutional study.

BACKGROUND: Transplant coronary artery disease (TCAD) limits survival in heart transplant recipients; however, its incidence in children is unknown. The purpose of this study was to determine the angiographic incidence of TCAD, potential risk factors, and outcomes in a large pediatric cohort. METHODS: From January 1993 to December 1, a total of 1,222 children, aged newborn to 17 years, underwent primary cardiac transplantation at 20 institutions. A total of 2,049 coronary angiograms were performed in 751 patients. All angiograms were graded for coronary disease and results were submitted to the Pediatric Heart Transplant Study database. We analyzed time-related freedom from graded severity and events from coronary disease, and we examined risk factors. RESULTS: The incidence of angiographic abnormalities at 1, 3, and 5 years was 2%, 9%, and 17%, respectively; however, moderate-to-severe disease occurred in only 6% at 5 years, compared with 15% in the adult transplant database (p <0.0001). The major risk factors were older recipient and donor age. Two or more episodes of rejection in the 1st year correlated with coronary disease (p = 0.05). Overall freedom from graft loss caused by primary TCAD was 99%, 96%, and 91% at 1, 5, and 9 years after heart transplantation, respectively. Death or graft loss occurred within 2 years of diagnosis in patients with severe disease; 24% of patients with any coronary disease died within 2 years. CONCLUSIONS: The incidence of TCAD in children is smaller than the incidence in adults, but increases with age. Graft loss is infrequent in children; however, severe coronary disease correlates with poor prognosis.

Scoring system to determine need for balloon atrial septostomy for restrictive interatrial communication in infants with hypoplastic left heart syndrome.

BACKGROUND: Restrictive interatrial communication (IAC) causes morbidity and mortality in infants with hypoplastic left heart syndrome awaiting cardiac transplantation. We sought to create a scoring system, based on echocardiographic and clinical findings, to serve as a guide for determining the need for balloon atrial septostomy (BAS). METHODS: We retrospectively reviewed echocardiograms of 44 infants with hypoplastic left heart syndrome. Infants were studied from the time of admission to the final end-point of transplantation, Norwood procedure, or death. Seventeen infants underwent BAS for clinical indications of oxygen saturation <80% in room air. Data collected included age at BAS, maximum velocity (V(max)), and IAC diameter throughout the clinical course. We assigned higher IAC scores to smaller IAC diameter, greater V(max) through the IAC, and lower oxygen saturation value. The minimum score was 3, and the maximum score was 9. RESULTS: Only 10% of infants with a score <6 at presentation required BAS, whereas 67% of those with scores > or =6 required BAS. Higher IAC scores at presentation were associated with earlier need for BAS (p = 0.04). CONCLUSIONS: The IAC scoring system can serve as a reliable clinical guide for identifying infants with hypoplastic left heart syndrome who are likely to require BAS for relief of critically restrictive IAC while awaiting cardiac transplantation.

Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients.

BACKGROUND: Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection. METHODS: Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient's immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine. RESULTS: A total of 1108 biopsies were performed in 269 children with a mean follow-up of 5 +/- 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1). on 3-drug immunosuppressive therapy; (2). with a recipient age >1 year; and (3). with a relatively lower cyclosporine level. CONCLUSIONS: These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up.

Usefulness of cardiac transplantation in children with visceral heterotaxy (asplenic and polysplenic syndromes and single right-sided spleen with levocardia) and comparison of results with cardiac transplantation in children with dilated cardiomyopathy.

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.