The arterial switch operation has excellent early outcomes. Although the majority of patients are growing into healthy adults, a small subset require reoperation for pulmonary stenosis as well as ...neoaortic root dilatation and neoaortic valve regurgitation, especially as follow-up increases. Challenging subgroups include patients with anomalous coronary anatomy, concomitant aortic arch obstruction, Taussig-Bing anomaly, ventricular septal defect, and low operative weight, and patients with an intact interventricular septum who present late.
Mucosal‐associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non‐lineage‐specific (surrogate) markers such as ...anti‐TRAV1‐2, CD161, IL‐18Rα and CD26. The development of MR1‐Ag tetramers now permits the specific identification of MAIT cells based on T‐cell receptor specificity. Here, we compare these approaches for identifying MAIT cells and show that surrogate markers are not always accurate in identifying these cells, particularly the CD4+ fraction. Moreover, while all MAIT cell subsets produced comparable levels of IFNγ, TNF and IL‐17A, the CD4+ population produced more IL‐2 than the other subsets. In a human ontogeny study, we show that the frequencies of most MR1 tetramer+ MAIT cells, with the exception of CD4+ MAIT cells, increased from birth to about 25 years of age and declined thereafter. We also demonstrate a positive association between the frequency of MAIT cells and other unconventional T cells including Natural Killer T (NKT) cells and Vδ2+ γδ T cells. Accordingly, this study demonstrates that MAIT cells are phenotypically and functionally diverse, that surrogate markers may not reliably identify all of these cells, and that their numbers are regulated in an age‐dependent manner and correlate with NKT and Vδ2+ γδ T cells.
This study uses MR1 tetramers to enumerate and phenotypically characterize human blood MAIT cells, and subsets thereof based on CD4 and CD8 expression. Furthermore MR1 tetramers are compared to the commonly used mAb‐based MAIT cell identification techniques.
Background Studies on long-term outcomes of the arterial switch operation (ASO) for transposition of the great arteries (TGA) are uncommon. Thus, we sought to determine the long-term outcomes for ...patients after ASO performed at a single institution over a 25-year period. Methods From 1983 to 2009, 618 patients underwent the ASO for TGA and were reviewed retrospectively. Results Overall early mortality was 2.8%. Risk factors for early death on multivariate analysis were resection of left ventricular outflow tract obstruction at time of ASO ( p = 0.001), weight less than 2.5 kg at time of ASO ( p < 0.001), associated aortic arch obstruction ( p = 0.043), and the need for postoperative extracorporeal membrane oxygenation ( p < 0.001). Mean follow-up time was 10.6 years (range 2 months to 26.1 years). Late mortality was 0.9%. Reintervention was significantly higher ( p < 0.001) in patients with ventricular septal defect or arch obstruction versus those without them (25.2% and 23.4% vs 5.9% at 15- year follow-up). Risk factors for late reintervention were left ventricular outflow tract obstruction at time of ASO ( p < 0.001) and a greater circulatory arrest time ( p < 0.001). Freedom from at least moderate neoaortic valve regurgitation for the entire cohort was 98.7% (95% confidence interval 96.8 to 99.5%) at 20 years. Mild neoaortic regurgitation was seen in 25.6% of patients at mean follow-up. All patients were free of arrhythmia and heart failure symptoms at last follow-up. Conclusions The ASO can be performed with good long-term results. Patients with associated ventricular septal defect and aortic arch obstruction warrant close follow-up.
Abstract Background Single-ventricle palliation (SVP) for children with unbalanced atrioventricular septal defect (uAVSD) is thought to carry a poor prognosis, but limited data have been reported. ...Methods We performed a retrospective review of children with uAVSD who underwent SVP at a single institution. Data were obtained from medical records and correspondence with general practitioners and cardiologists. Results Between 1976 and 2016, a total of 139 patients underwent SVP for uAVSD. A neonatal palliative procedure was performed in 83.5% of these patients (116 of 139), and early mortality occurred in 11.2% (13 of 116). Ninety-four patients underwent stage II palliation, with an early mortality of 6.4% (6 of 94). Eighty patients (57.6%) underwent Fontan completion, with an early mortality of 3.8% (3 of 80). Interstage mortality was 11.7% (12 of 103) between stages I and II and 17.0% (15 of 88) between stage II and Fontan. Long-term survival was 66.5% (95% confidence interval CI, 57.9%-73.9%) at 5 years, 64.4% (95% CI, 55.5%-72.0%) at 15 years, and 57.8% (95% CI, 47.5%-66.8%) at 25 years. Survival post-Fontan was 94.9% (95% CI, 86.9%-98.0%) at 5 years, 92.0% (95% CI, 80.6%-96.8%) at 15 years, and 82.4% (95% CI, 61.5%-92.6%) at 25 years. Risk factors associated with death or transplantation were aortic atresia (hazard ratio HR, 5.3; P = .03) and hypoplastic aortic arch (HR, 2.5; P = .02). Atrioventricular valve operations were required in 31.7% of the patients (44 of 139), with 31.8% of them (14 of 44) requiring a further operation. Conclusions Children undergoing SVP for uAVSD have substantial mortality, with <60% survival at 25 years. However, survival of children who achieve Fontan completion is better than has been reported previously.
Abstract Objective The surgical indication, timing, strategy, and surgical technique for anatomic correction of congenitally corrected transposition of the great arteries are challenging. We ...evaluated the long-term results at The Royal Children's Hospital Melbourne. Methods Review of 32 successive anatomic corrections between 1996 and 2015. Results Twenty-one double-switch (66%), 6 Senning/Bex-Nikaidoh (19%), and 5 Senning/Rastelli (16%) procedures were performed (median age, 1.9 years). Median follow-up was 5.4 years with 4 deaths and 1 heart transplant. Cumulative incidence of late reoperation was 8%, 29%, and 59% at 1, 5, and 10 years, respectively. Twenty-six patients had full follow-up with native hearts. Nineteen had normal left ventricle (LV) function. Late LV dysfunction, mostly mild, was not related to needing a pacemaker ( P = .4) or a pulmonary artery band (PAB) ( P = .08). Previous PAB was linked to the need for aortic valve surgery or neoaortic regurgitation moderate or greater ( P = .03). Six required Senning revision. The introduction of the Shumacker modification of the Senning has generated stable pulmonary venous pathways. Six patients developed postoperative iatrogenic atrioventricular block dependent on a permanent pacemaker. Conclusions Anatomic correction is a surgical challenge. It provides excellent functional outcomes in survivors with a significant need for reoperation and a definite risk of death or transplantation. Normal LV function should be expected in most patients. LV dysfunction was not linked to PAB or pacemaker requirement but surgery without LV training had better long-term LV function. The Shumacker modification provided stable venous pathways. Iatrogenic atrioventricular block remains a challenge.
We aimed to assess the long-term outcomes of children with isolated congenital aortic stenosis who underwent primary aortic valve repair.
Records of all children (n = 111) with isolated congenital ...aortic stenosis who underwent primary aortic valve repair between 1980 and 2016 were reviewed. An optimal operative outcome consisted of a residual left ventricular outflow tract peak systolic gradient <35 mm Hg and trivial or less aortic insufficiency.
Median age at surgery was 0.4 years (interquartile range, 1 month-7.9 years) and median weight at surgery was 7.0 kg (interquartile range, 3.7-25.0 kg). Fifty-two patients (46.8%; 52/111) underwent aortic valve repair with the use of patch material. Early mortality was 0.9% (1/111). Late mortality was 0.9% (1/110). Freedom from aortic valve reoperation was 52.1% (95% CI, 38.7-63.8) at 10 years. Freedom from aortic valve replacement was 67.9% (95% CI, 55.4-77.5) at 10 years. An optimal outcome was achieved in 48 patients (43.2%; 48/111). At 10 years, freedom from aortic valve reoperation was 78.2% (95% CI, 63.1-87.8) in patients with an optimal outcome, compared with 39.4% (95% CI, 22.8-55.6) in those with a suboptimal outcome (P = .03). Tricuspid aortic valve was associated with a suboptimal outcome (P = .01).
Aortic valve repair achieves relief of congenital aortic stenosis with very low early mortality and excellent long-term survival, even in neonates. Although nearly half of the patients required aortic valve reoperation by 10 years, two-thirds of the patients remain free from aortic valve replacement. An optimal outcome was more commonly achieved with bicuspid aortic valves compared with tricuspid aortic valves.
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Despite in-depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals governing postnatal maturation of the human heart.
Single-nucleus RNA ...sequencing of 54 140 nuclei from 9 human donors was used to profile transcriptional changes in diverse cardiac cell types during maturation from fetal stages to adulthood. Bulk RNA sequencing and the Assay for Transposase-Accessible Chromatin using sequencing were used to further validate transcriptional changes and to profile alterations in the chromatin accessibility landscape in purified cardiomyocyte nuclei from 21 human donors. Functional validation studies of sex steroids implicated in cardiac maturation were performed in human pluripotent stem cell-derived cardiac organoids and mice.
Our data identify the progesterone receptor as a key mediator of sex-dependent transcriptional programs during cardiomyocyte maturation. Functional validation studies in human cardiac organoids and mice demonstrate that the progesterone receptor drives sex-specific metabolic programs and maturation of cardiac contractile properties.
These data provide a blueprint for understanding human heart maturation in both sexes and reveal an important role for the progesterone receptor in human heart development.
We sought to determine the influence of coronary artery anatomy on mortality in more than 1000 children undergoing the arterial switch operation.
All patients who underwent an arterial switch ...operation were identified from 2 hospital databases and reviewed retrospectively. Coronary anatomy was recorded from operative reports using the Leiden classification.
An arterial switch operation was performed in 1033 children between 1983 and 2013. Coronary anatomy was normal in 697 patients (67%). The most common type of anomalous coronary anatomy was the circumflex coronary artery arising from sinus 2 (in 152 patients 15%). Forty-seven patients (4.5%) had all coronary arteries arising from a single sinus. Of these 47 patients, 34 patients (3.3%) had a true single coronary artery. Fifty-two patients (5.0%) had an intramural coronary artery. Overall early mortality was 3.3% (34 out of 1033 patients) over the 30-year period. Early mortality was 3.0% (21 out of 697) for patients with normal coronary anatomy and 3.9% (13 out of 336) for any type of anomalous coronary anatomy. Early mortality was 3.3% (5 out of 152) for patients with the circumflex coronary artery arising from sinus 2, 6.4% (3 out of 47) for patients with all coronary arteries arising from a single sinus, and 5.9% (2 out of 34) for patients with a true single coronary artery. Early mortality for patients with intramural coronaries was 1.9% (1 out of 52). No coronary pattern was found to be a risk factor for mortality.
Patients with anomalous coronary artery anatomy had higher rates of early mortality after the arterial switch operation but this was not statistically significant. Coronary artery reoperations were rare.
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