Survival does not differ by annual center transplant volume-A Pediatric Heart Transplant Society Registry study.

BACKGROUND: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high-risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. METHODS: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan-Meier analysis. RESULTS: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p = .75), in patients with CHD (p = .79) or in patients with cardiomyopathy (p = .23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p = .17, p = .31, and p = .10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p < .0001), though no discernible pattern related to high or low center volume. CONCLUSIONS: Outcomes are similar among transplant centers of all sizes, including for high-risk patient groups with CHD. Future work is needed to understand how patient-specific risk factors may vary among centers of various sizes and whether this influences patient outcomes.

Hypertension: An Important But Reversible Cause of Systolic Dysfunction in a Cohort of Pediatric Patients.

Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. We aimed to describe the presentation and outcomes of pediatric CDHTN and identify clinical features associated with resolution of dysfunction. A single-center retrospective cohort study of patients ≤ 21 years with CDHTN from January 2005-September 2020 was performed. Patients with systolic dysfunction without another cause, blood pressure > 95th percentile, and physician judgment that dysfunction was secondary to hypertension were included. Demographics, clinical characteristics, echocardiographic findings, and outcomes were examined using Fisher's exact and Mann-Whitney U tests. Multiple correspondence analysis was used to explore the relationship of resolution of dysfunction to clinical features. Thirty-four patients were analyzed at a median age of 10.9 (IQR 0.3-16.9) years. Patients were divided into groups < 1 year (n = 12) and ≥ 1 year (n = 22). Causes of hypertension were varied by age, with renovascular disease most common in infants (42%) and medical renal disease most common in older patients (77%). Echocardiography demonstrated mild LV dilation (median LV end-diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.4). Most patients (81%) had resolution of dysfunction, particularly infants (92%). One patient died and one patient was listed for heart transplant. None required mechanical circulatory support (MCS). No clinical features were statistically associated with resolution of dysfunction. Hypertension is an important but reversible cause of systolic dysfunction in children. Patients are likely to recover with low mortality and low utilization of MCS or transplantation. Further studies are needed to confirm features associated with resolution of dysfunction.

Comparison of treatment strategies for neonates with tetralogy of Fallot and pulmonary atresia.

OBJECTIVE: Neonates with tetralogy of Fallot and pulmonary atresia (TOF/PA) but no major aorta-pulmonary collaterals are dependent on the arterial duct for pulmonary blood flow and require early intervention, either by primary (PR) or staged repair (SR) with initial palliation (IP) followed by complete repair (CR). The optimal approach has not been established. METHODS: Neonates with TOF/PA who underwent PR or SR were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Outcomes were compared between PR and SR (IP + CR) strategies. Propensity scoring was used to adjust for baseline differences. The primary outcome was mortality. Secondary outcomes included complications, length of stay, cardiopulmonary bypass and anesthesia times, reintervention (RI), and pulmonary artery (PA) growth. RESULTS: Of 282 neonates, 106 underwent PR and 176 underwent SR (IP: 144 surgical, 32 transcatheter). Patients who underwent SR were more likely to have DiGeorge syndrome and greater rates of mechanical ventilation before the initial intervention. Mortality was not significantly different. Duration of mechanical ventilation, inotrope use, and complication rates were similar. Cumulative length of stay, cardiopulmonary bypass, and anesthesia times favored PR (P ≤ .001). Early RI was more common in patients who underwent SR (rate ratio, 1.42; P = .003) but was similar after CR (P = .837). Conduit size at the time of CR was larger with SR. Right PA growth was greater with PR. CONCLUSIONS: In neonates with TOF/PA, SR is more common in greater-risk patients. Accounting for this, SR and PR strategies have similar mortality. Perioperative morbidities, RI, and right PA growth generally favor PR, whereas SR allows for larger initial conduit implantation.

Management of circulatory failure after Fontan surgery.

With improvement in survival after Fontan surgery resulting in an increasing number of older survivors, there are more patients with a Fontan circulation experiencing circulatory failure each year. Fontan circulatory failure may have a number of underlying etiologies. Once Fontan failure manifests, prognosis is poor, with patient freedom from death or transplant at 10 years of only about 40%. Medical treatments used include traditional heart failure medications such as renin-angiotensin-aldosterone system blockers and beta-blockers, diuretics for symptomatic management, antiarrhythmics for rhythm control, and phosphodiesterase-5 inhibitors to decrease PVR and improve preload. These oral medical therapies are typically not very effective and have little data demonstrating benefit; if there are no surgical or catheter-based interventions to improve the Fontan circulation, patients with severe symptoms often require inotropic medications or mechanical circulatory support. Mechanical circulatory support benefits patients with ventricular dysfunction but may not be as useful in patients with other forms of Fontan failure. Transplant remains the definitive treatment for circulatory failure after Fontan, but patients with a Fontan circulation face many challenges both before and after transplant. There remains significant room and urgent need for improvement in the management and outcomes of patients with circulatory failure after Fontan surgery.

Comparison of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot.

BACKGROUND: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention. OBJECTIVES: This study sought to perform a balanced multicenter comparison of staged repair (SR) (initial palliation [IP] and subsequent complete repair [CR]) versus primary repair (PR) treatment strategies. METHODS: Consecutive neonates with sTOF who underwent IP or PR at ≤30 days of age from 2005 to 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. The primary outcome was death. Secondary outcomes included component (IP, CR, PR) and cumulative (SR): hospital and intensive care unit lengths of stay; durations of cardiopulmonary bypass, anesthesia, ventilation, and inotrope use; and complication and reintervention rates. Outcomes were compared using propensity score adjustment. RESULTS: The cohort consisted of 342 patients who underwent SR (IP: surgical, n = 256; transcatheter, n = 86) and 230 patients who underwent PR. Pre-procedural ventilation, prematurity, DiGeorge syndrome, and pulmonary atresia were more common in the SR group (p ≤0.01). The observed risk of death was not different between the groups (10.2% vs 7.4%; p = 0.25) at median 4.3 years. After adjustment, the hazard of death remained similar between groups (hazard ratio: 0.82; 95% confidence interval: 0.49 to 1.38; p = 0.456), but it favored SR during early follow-up (<4 months; p = 0.041). Secondary outcomes favored the SR group in component analysis, whereas they largely favored PR in cumulative analysis. Reintervention risk was higher in the SR group (p = 0.002). CONCLUSIONS: In this multicenter comparison of SR or PR for management of neonates with sTOF, adjusted for patient-related factors, early mortality and neonatal morbidity were lower in the SR group, but cumulative morbidity and reinterventions favored the PR group, findings suggesting potential benefits to each strategy.

Cytotoxic T-Lymphocyte-Associated Protein 4 Haploinsufficiency-Associated Inflammation Can Occur Independently of T-Cell Hyperproliferation.

Located contiguously on the long arm of the second chromosome are gene paralogs encoding the immunoglobulin-family co-activation receptors CD28 and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). CD28 and CTLA4 share the same B7 ligands yet each provides opposing proliferative signals to T cells. Herein, we describe for the first time two unrelated subjects with coexisting CD28 and CTLA4 haploinsufficiency due to heterozygous microdeletions of chromosome 2q. Although their clinical phenotype, multi-organ inflammatory disease, is superficially similar to that of CTLA4 haploinsufficient autoimmune lymphoproliferative syndrome type V (ALPS5) patients, we demonstrate our subjects' underlying immunopathology to be distinct. Unlike ALPS5 T cells which hyperproliferate to T-cell receptor-mediated activation and infiltrate organs, T cells from our subjects are hypoproliferative and do not. Instead of T cell infiltrates, biopsies of affected subject tissues demonstrated infiltrates of lineage negative lymphoid cells. This histologic feature correlated with significant increases in circulating type 3 innate lymphoid cells (ILC3s) and ILC3 cytokines, interleukin 22, and interleukin-17A. CTLA4-Ig monotherapy, which we trialed in one subject, was remarkably effective in controlling inflammatory diseases, normalizing ILC3 frequencies, and reducing ILC3 cytokine concentrations.