ABSTRACT
IL-23/Th17 pathway has been identified to sustain inflammatory condition in several autoimmune diseases and therefore being targeted in various therapeutic and effective approaches. Patients affected with autoimmune myasthenia gravis exhibit a disease effector tissue, the thymus, that harbors ectopic germinal centers that sustain production of auto-antibodies, targeting proteins located in the neuromuscular junction, cause of the organ-specific chronic autoimmune disease. The present study aims to investigate the IL-23/Th17â¯cell pathway in the thymic inflammatory and pathogenic events. We found that thymuses of MG patients displayed overexpression of Interleukin-17, signature cytokine of activated Th17â¯cells. This activation was sustained by a higher secretion of Interleukin-23 by TEC, in addition to the increased expression of cytokines involved in Th17â¯cell development. The overexpression of Interleukin-23 was due to a dysregulation of interferon type I pathway. Besides, Interleukin-17 secreted, and Th17â¯cells were localized around thymic ectopic germinal centers. These cells expressed podoplanin, a protein involved in B-cell maturation and antibody secretion. Finally, production of Interleukin-23 was also promoted by Interleukin-17 secreted itself by Th17â¯cells, highlighting a chronic loop of inflammation sustained by thymic cell interaction. Activation of the IL-23/Th17 pathway in the thymus of autoimmune myasthenia gravis patients creates an unstoppable loop of inflammation that may participate in ectopic germinal center maintenance. To alleviate the physio-pathological events in myasthenia gravis patients, this pathway may be considered as a new therapeutic target.
Subject(s)
Inflammation/immunology , Interleukin-17/metabolism , Interleukin-23/metabolism , Myasthenia Gravis/immunology , Th17 Cells/immunology , Thymus Gland/metabolism , Adolescent , Adult , Cells, Cultured , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Membrane Glycoproteins/metabolism , Middle Aged , Signal Transduction , Thymus Gland/pathology , Young AdultABSTRACT
OBJECTIVES: To analyse the feasibility and effectiveness in humanitarian practice of surgical management of children with single-ventricle heart condition. METHODS: Retrospective study of children with a single ventricle, managed by the association Mécénat-Chirurgie Cardiaque since 1996, with long-term follow-up after their return home. RESULTS: Of the 138 children in our cohort, 119 had one or more surgeries (180 procedures): palliative surgery alone (systemic-pulmonary anastomosis or banding), 41; partial cavo-pulmonary connection, 47; total cavo-pulmonary connection (mean age 8.5 years), 31. Operative mortality is 5.5%. After a mean follow-up of 5.6 years, 18 children (13%) were lost to follow-up. Survival at 10 years is 79% in children receiving surgery (palliative only, 72%; partial cavo-pulmonary connection, 77%; total cavo-pulmonary connection, 97%) versus 29% in children with no surgical intervention. The prognosis is better for tricuspid atresia and double-inlet left ventricle (86 and 83% survival at 10 years) than for double-outlet right ventricle or complete atrio-ventricular canal defect (64 and 68% at 5 years). CONCLUSION: The surgery of the single ventricle in humanitarian medicine allows a very satisfactory survival after one or more surgeries tending towards a total cavo-pulmonary connection as soon as possible.
Subject(s)
Fontan Procedure/methods , Heart Defects, Congenital/surgery , Heart Ventricles/abnormalities , Heart Ventricles/surgery , Child , Child, Preschool , Developing Countries , Female , Follow-Up Studies , Fontan Procedure/statistics & numerical data , France , Heart Defects, Congenital/mortality , Humans , Male , Palliative Care/methods , Relief Work , Retrospective Studies , Risk Factors , Survival Rate/trends , Treatment OutcomeABSTRACT
Prematurity is a recognized risk factor for morbidity and mortality following cardiac surgery. Postoperative and long-term outcomes after cardiac surgery performed in the preterm period are poorly described. The aim of this study was to analyze a population of preterm neonates operated on for critical congenital heart disease (CHD) before 37 weeks of gestational age (wGA) with special attention given to early and late mortality and morbidity. Between 2000 and 2013, 28 preterm neonates (median gestational age (GA) 34.3 weeks) underwent cardiopulmonary bypass (CPB) surgery for critical CHD before 37 wGA; records were retrospectively reviewed. All patients except three with single ventricle physiology had a single-stage anatomic repair. Overall mortality was 43 % (95 % CI 25-62). Risk factors for death were birth weight (p = 0.032) and weight at surgery (p = 0.037), independently of GA, preoperative status, CPB and aortic clamp time. Seven patients, including those with univentricular hearts, died during the postoperative period, and five in the first year after surgery. Median follow-up was 5.9 years (range 1 month-12.8 years). Kaplan-Meier survival rate was 75 % (95 % CI 59-91) at 1 month, and 57 % (95 % CI 39-75) at 1 and 5 years. Eight patients required reoperations after a delay of 2.8 ± 1.3 months; eight had bronchopulmonary dysplasia. At the end of follow-up, nine patients were asymptomatic. One-stage biventricular repair for critical CHD on preterm neonates was feasible. Mortality remained high but acceptable, mainly confined to the first postoperative year and related to small weight. Despite reoperations, long-term clinical status was good in most survivors. Further long-term prospective investigations are necessary to evaluate neurodevelopmental outcomes.
Subject(s)
Cardiac Surgical Procedures/mortality , Cardiopulmonary Bypass/mortality , Gestational Age , Heart Defects, Congenital/surgery , Postoperative Complications/mortality , Survival Rate , Birth Weight , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cardiopulmonary Bypass/adverse effects , Cardiopulmonary Bypass/methods , Female , Heart Defects, Congenital/mortality , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Male , Postoperative Complications/epidemiology , Pregnancy , Prospective Studies , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease mediated mainly by anti-acetylcholine receptor (AChR) antibodies. The thymus plays a primary role in MG pathogenesis. As we recently showed an inflammatory and antiviral signature in MG thymuses, we investigated whether pathogen-sensing molecules could contribute to an anti-AChR response. METHODS: We studied the effects of toll-like receptor agonists on the expression of α-AChR and various tissue-specific antigens (TSAs) in human thymic epithelial cell (TEC) cultures. As polyinosinic-polycytidylic acid (poly[I:C]), which mimics double-stranded RNA (dsRNA), stimulated specifically α-AChR expression, the signaling pathways involved were investigated. In parallel, we analyzed the expression of dsRNA-signaling components in the thymus of MG patients, and the relevance of our data was investigated in vivo in poly(I:C)-injected mice. RESULTS: We demonstrate that dsRNA signaling induced by poly(I:C) specifically triggers the overexpression of α-AChR in TECs and not of other TSAs. A poly(I:C) effect was also observed on MG TECs. This induction is mediated through toll-like receptor 3 (TLR3) and protein kinase R (PKR), and by the release of interferon (IFN)-ß. In parallel, human MG thymuses also display an overexpression of TLR3, PKR, and IFN-ß. In addition, poly(I:C) injections specifically increase thymic expression of α-AChR in wild-type mice, but not in IFN-I receptor knockout mice. These injections also lead to an anti-AChR autoimmune response characterized by a significant production of serum anti-AChR antibodies and a specific proliferation of B cells. INTERPRETATION: Because anti-AChR antibodies are highly specific for MG and are pathogenic, dsRNA-signaling activation could contribute to the etiology of MG.
Subject(s)
Myasthenia Gravis/genetics , Myasthenia Gravis/immunology , Poly I-C/immunology , RNA, Double-Stranded/immunology , Signal Transduction/genetics , Adolescent , Adult , Animals , Antibody Specificity , Autoantibodies/blood , Autoantibodies/immunology , Autoimmunity/genetics , Autoimmunity/immunology , B-Lymphocytes/immunology , Cells, Cultured , Gene Expression/drug effects , Gene Expression/immunology , Humans , Infant , Interferon Inducers/immunology , Interferon Inducers/metabolism , Interferon Inducers/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Myasthenia Gravis/etiology , Poly I-C/metabolism , Poly I-C/pharmacology , RNA, Double-Stranded/metabolism , RNA, Double-Stranded/pharmacology , RNA, Messenger/genetics , Receptors, Cholinergic/genetics , Receptors, Cholinergic/immunology , Signal Transduction/immunology , Thymus Gland/cytology , Young AdultABSTRACT
OBJECTIVES: The goal of this retrospective multicentre study was to present late surgical outcomes of the treatment of children with double outlet right ventricle (DORV) coming from emerging countries. METHODS: The Mécénat Chirurgie Cardiaque brings to France for surgery selected children with simple and complex congenital diseases, including DORV. The patients are operated on in 9 hospitals that specialize in paediatric cardiac surgery. Data are collected from the Mécénat Chirurgie Cardiaque comprehensive database, with a strict postoperative follow-up. The patients included only those who had biventricular repair of DORV with 2 viable ventricles. According to the classification of the Eleventh Revision of the International Classification of Diseases, DORV was defined as a congenital cardiovascular malformation in which both great arteries arise entirely or predominantly from the morphologically right ventricle. RESULTS: From January 1996 to January 2022, a total of 81 consecutive DORV biventricular repair operations were performed. There were 6 subtypes of DORV divided into 2 groups: DORV-committed ventricular septal defect (VSD): DORV-VSD (n = 25), DORV-Fallot (n = 34), DORV-transposition of the great arteries (n = 5); and DORV-non-committed (nc) VSD: DORV-ncVSD-no pulmonary stenosis (PS) (n = 7), DORV-ncVSD-PS (n = 5) and DORV-atrioventricular septal defect (AVSD)-PS (n = 5). Four Fontan patients were excluded. Three patients were lost to follow-up (3.4%). The overall perioperative mortality was 7.4% ± 2.6%, 6/81 (95% confidence interval: 2.8%-15.4%) ranging from 0% in DORV-AVSD-PS to 14% for DORV-ncVSD-no PS. The overall 10-year survival was 86%. The early mortality of DORV-ncVSD at 5.9% ± 2.4% (1/17) was similar to that of DORV-committed VSD at 7.8% ± 2.7% (5/64) (P = 0.79). There was a trend towards an optimal outcome for the arterial switch operation and the DORV-AVSD-PS repair. VSD enlargement was significantly more frequent in DORV-ncVSD at 42% (5/12) (P = 0.001). There were low numbers in the complex groups. The number of Fontan cases was noticeably low. The aorta located entirely on the right ventricle represents the fundamental anomaly and the surgical challenge of DORV. CONCLUSIONS: Overall survival at 10 years was 86%. This study shows a trend towards satisfactory early and late outcomes in BVR of simple DORV with committed VSD, compared to complex DORV with ncVSD.
Subject(s)
Cardiac Surgical Procedures , Double Outlet Right Ventricle , Heart Septal Defects , Pulmonary Valve Stenosis , Transposition of Great Vessels , Child , Humans , Infant , Cardiac Surgical Procedures/adverse effects , Double Outlet Right Ventricle/surgery , Transposition of Great Vessels/surgery , Treatment Outcome , Retrospective StudiesABSTRACT
INTRODUCTION AND OBJECTIVES: Diagnosis, management, and surgical decision-making in children and adults with congenital heart disease are largely based on echocardiography findings. A recent development in cardiac imaging is fusion of different imaging modalities. Our objective was to evaluate the feasibility of computed tomography (CT) and 3-dimensional (3D) transthoracic echocardiography (TTE) fusion in children and adults with congenital heart disease. METHODS: We prospectively included 14 patients, 13 of whom had congenital heart disease, and who underwent both CT and 3D TTE as part of their usual follow-up. We described the steps required to complete the fusion process (alignment, landmarks, and superimposition), navigation, and image evaluation. RESULTS: Median age was 9.5 [2.7-15.7] years, 57% were male, and median body surface area was 0.9 m2 [0.6-1.7]. Congenital heart disease was classified as simple (n=4, 29%), moderate (n=4, 29%), or complex (n=6, 42%). 3D TTE-CT fusion was successful in all patients. Median total time to complete the fusion process was 735 [628-1163] seconds, with no significant difference according to the degree of complexity of the defects. Landmarks were significantly modified in complex congenital heart disease. CONCLUSIONS: We established the feasibility and accuracy of 3D TTE-CT fusion in a population of children and adults with a variety of congenital heart diseases. The simultaneous visualization of many intracardiac structures may help to understand the anatomical features of congenital heart disease without limitations regarding age, weight, or complexity of the congenital defects.
Subject(s)
Echocardiography, Three-Dimensional , Heart Defects, Congenital , Child , Adult , Humans , Male , Female , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/surgery , Echocardiography/methods , Heart/diagnostic imaging , Echocardiography, Three-Dimensional/methods , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Children with severe congenital heart disease (CHD) are rarely treated in developing countries and have very little to no chance to survive in their local environment. Mécénat Chirurgie Cardiaque (MCC) flies to France children with CHD from developing countries. This report focuses on the early, mid, and late outcomes of 531 children with severe CHD sent to MCC for surgery from 1996 to 2019. METHODS: The inclusion criteria were based on diagnosis and not on procedure. MCC is present in 66 countries and has developed a robust staff, including 12 permanent employees and 700 volunteers, with 350 host families based in France, 120 local correspondents, and 100 local physicians. Since 1996, MCC has organized a basic training of local pediatric cardiologists yearly, offering a free 1-month training course. Over time, MCC could count on a pool of doctors trained in basic pediatric cardiology. Flights were secured by the Aviation Sans Frontieres Foundation. Nine French centers performed the surgeries. A robust follow-up was conducted in all the nations where MCC operates. RESULTS: The most frequent pathologies were single ventricle (n = 126), double-outlet right ventricle (n = 116), pulmonary atresia with ventricular septal defect (n = 68), transposition of the great arteries with ventricular septal defect and transposition of the great arteries with intact ventricular septum (n = 61), arterial trunk (n = 39), transposition of the great arteries with ventricular septal defect and left ventricle outflow tract obstruction (n = 35), complete atrioventricular septal defect (n = 18), congenitally corrected transposition of the great arteries (n = 16), and so on. The median age was 5.4 years (range, 1 month-26 years). The mean perioperative mortality was 5.5% (29 out of 531) (95% confidence limit, 3.5%-7.4%). The follow-up was 91.3%, with a mean follow-up of 5.1 years. The global actuarial survival at 5, 10, and 15 years was, respectively, 85%, 83%, and 74%. There was a significant higher late mortality for patients surviving only with a Blalock-Taussig shunt (P = .001). CONCLUSIONS: Operating on 531 children with severe CHD from developing nations was achieved with satisfactory early and long-term results. Children with severe CHD are rarely operated on in developing nations. Programs like MCC's offer a viable option to save these children born with severe CHD.
Subject(s)
Cardiac Surgical Procedures , Developing Countries , Heart Defects, Congenital/surgery , Adolescent , Adult , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/mortality , Child , Child, Preschool , Databases, Factual , Female , France , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/mortality , Heart Defects, Congenital/physiopathology , Humans , Infant , Male , Medical Missions , Postoperative Complications/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Young AdultABSTRACT
OBJECTIVES: Anomalous aortic origin of the coronary artery (AAOCA) with an interarterial ± an intramural course is a rare anomaly that carries a high risk of ischaemic events and even sudden death. The unroofing of the intramural course has been adopted as the gold standard surgical treatment. However, some anatomical forms need alternative techniques. METHODS: We reviewed the surgical cohort with AAOCA managed at our institution between 2005 and 2019 and analysed the anatomical and clinical outcomes. RESULTS: Thirty-nine patients underwent surgical interventions. The median age was 14 years (10-26 years). Twenty-eight patients (72%) had right AAOCA, and 11 (28%) had left AAOCA. Thirty-one (80%) patients presented with symptoms. The symptoms were chest pain in 22 patients (56%), syncope in 5 patients (13%), cardiac arrest during exercise in 2 patients (5%), dyspnoea in 6 patients (15%) and dizziness in 13 patients (33%). An ischaemic test was performed in 32 patients: Only 4 patients (10%) had positive results from the ischaemic test. All patients had computed tomography angiography scans to confirm the precise anatomical features of the anomaly. Repair techniques included 30 unroofing procedures (77%) with an associated translocation of the pulmonary artery for 11 patients in our early experience. In 6 patients the unroofing procedure was not feasible because of the absence of an intramural distinct segment or was judged intraoperatively not appropriate. A reimplantation of the anomalous coronary artery was performed in 2 patients (5%); 3 patients had coronary artery bypass grafting procedures (7%); and 3 (8%) had an isolated translocation of the pulmonary artery. There were no early or late deaths. All patients were free of symptoms. Computed tomography angiography scans performed in 31 cases showed a patent, non-restrictive coronary artery ostium. Seventeen patients underwent postoperative ischaemia testing and showed no evidence of ischaemia. CONCLUSIONS: Surgical correction in AAOCA is mandatory both for symptomatic and for asymptomatic patients with evidence of myocardial ischaemia under stress or with a restricted coronary artery segment. Surgical unroofing remains the gold standard but is not appropriate for all forms: alternative techniques should be considered. Surgical results are promising.
Subject(s)
Coronary Vessel Anomalies , Coronary Vessels , Adolescent , Aorta , Chest Pain , Coronary Angiography , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessel Anomalies/surgery , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Humans , Retrospective StudiesABSTRACT
Heart failure is the main cause of death in patients with pulmonary arterial hypertension and congenital heart disease. We used an original approach in a 15-year-old girl with rapidly progressive right heart failure secondary to severe pulmonary arterial hypertension and partial anomalous pulmonary venous return. After surgical congenital heart defect repair on cardiopulmonary bypass, she was weaned off bypass using a central Novalung for 11 days, then started on triple specific pulmonary vasodilator therapy.
Subject(s)
Lung Transplantation , Preoperative Care/methods , Pulmonary Arterial Hypertension/therapy , Scimitar Syndrome/therapy , Adolescent , Female , Humans , Pulmonary Arterial Hypertension/complications , Scimitar Syndrome/complicationsABSTRACT
The thymus is involved in autoimmune Myasthenia gravis (MG) associated with anti-acetylcholine (AChR) antibodies. In MG, thymic regulatory T cells (Treg) are not efficiently suppressive, and conventional T cells (Tconv) are resistant to suppression. To better understand the specific role of the thymus in MG, we compared the phenotype and function of peripheral and thymic Treg and Tconv from controls and MG patients. Suppression assays with thymic or peripheral CD4 + T cells showed that the functional impairment in MG was more pronounced in the thymus than in the periphery. Phenotypic analysis of Treg showed a significant reduction of resting and effector Treg in the thymus but not in the periphery of MG patients. CD31, a marker lost with excessive immunoreactivity, was significantly reduced in thymic but not blood resting Treg. These results suggest that an altered thymic environment may explain Treg differences between MG patients and controls. Since thymic epithelial cells (TECs) play a major role in the generation of Treg, we co-cultured healthy thymic CD4 + T cells with control or MG TECs and tested their suppressive function. Co-culture with MG TECs consistently hampers regulatory activity, as compared with control TECs, suggesting that MG TECs contribute to the immune regulation defects of MG CD4 + T cells. MG TECs produced significantly higher thymic stromal lymphopoietin (TSLP) than control TECs, and a neutralizing anti-TSLP antibody partially restored the suppressive capacity of Treg derived from co-cultures with MG TECs, suggesting that TSLP contributed to the defect of thymic Treg in MG patients. Finally, a co-culture of MG CD4 + T cells with control TECs restored numbers and function of MG Treg, demonstrating that a favorable environment could correct the immune regulation defects of T cells in MG. Altogether, our data suggest that the severe defect of thymic Treg is at least partially due to MG TECs that overproduce TSLP. The Treg defects could be corrected by replacing dysfunctional TECs by healthy TECs. These findings highlight the role of the tissue environment on the immune regulation.
Subject(s)
Blood Cells/immunology , Epithelial Cells/physiology , Myasthenia Gravis/immunology , T-Lymphocytes, Regulatory/immunology , Thymus Gland/immunology , Adolescent , Adult , Autoantibodies/metabolism , Cells, Cultured , Child , Coculture Techniques , Cytokines/metabolism , Female , Homeostasis , Humans , Immunomodulation , Infant, Newborn , Male , Receptors, Cholinergic/immunology , Young Adult , Thymic Stromal LymphopoietinABSTRACT
OBJECTIVES: Absent pulmonary valve syndrome is a rare congenital heart disease with severe airway compression due to dilatation of the pulmonary arteries (PAs). We investigated risk factors for death and prolonged mechanical ventilation (>7 days) and a threshold PA size for these outcomes. METHODS: This retrospective 2-centre cohort study included 68 patients with complete repair between January 1996 and December 2015. RESULTS: Median age at repair was 3.9 months (1.3-8.7 months), and median weight was 5 kg (4-7 kg). The mortality rate before hospital discharge was 12%, and the mortality rate at last follow-up was 19%. In multivariable analysis, risk factors for death were higher Nakata index [hazard ratio (HR) 1.001, 95% confidence interval (CI) 1.001-1.002; P < 0.001] and lower SpO2 (HR 1.06, 95% CI 1.02-1.09; P = 0.002). The accuracy of the Nakata index to predict death was excellent (area under the curve at 6 months: 0.92; P = 0.010). A Nakata index above 1500 mm2/m2 predicted mortality at 6 months with a sensitivity of 98% and a specificity of 82%. Twenty-five patients (37%) had prolonged mechanical ventilation. The only multivariable risk factor for prolonged ventilation was lower weight at repair (odds ratio 2.9, 95% CI 1.3-6.7; P = 0.008). Neither PA plasty nor the LeCompte manoeuvre had a protective effect on mortality or prolonged ventilation. A Nakata index above 1500 mm2/m2 remained a risk factor for mortality (P = 0.022) in patients who had a PA plasty or the LeCompte manoeuvre. CONCLUSIONS: In patients with absent pulmonary valve syndrome, the Nakata index predicts mortality with a cut-off of 1500 mm2/m2. Lower weight at repair is the only multivariable risk factor for prolonged ventilation. Neither PA plasty nor the LeCompte manoeuvre had a protective effect on these outcomes.
Subject(s)
Heart Defects, Congenital , Pulmonary Atresia , Pulmonary Valve , Cohort Studies , Humans , Pulmonary Artery , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Cardiac magnetic resonance (CMR) imaging with velocity encoding along all three directions of flow, known as 4DFlow CMR, provides both anatomical and functional information. Few data are available on the usefulness of 4DFlow CMR in everyday practice. Here, our objective was to investigate the usefulness of 4DFlow CMR for assessing congenital heart disease (CHD) in everyday practice. METHODS: From 2017 to 2019, consecutive patients who underwent 4DFlow CMR were included prospectively at a single high-volume centre. The parameters recommended by an expert's consensus statement for each diagnosis (congenital valvulopathy, septal defect, complex CHD, tetralogy of Fallot, aortic abnormalities) were assessed by two blinded experienced readers. 4DFlow CMRs that provided all recommended parameters were considered successful. Inter-observer and intra-observer agreement were investigated. RESULTS: We included 187 adults and 60 children covering broad ranges of weight (4.5-142â¯kg) and age (0.1-67â¯years). 4DFlow CMR was always the second-line imaging modality, after inconclusive echocardiography, and was successful in 231/247 (91%) patients, with no significant difference between children and adults (54/60, 90%; and 177/187, 95%; respectively; pâ¯=â¯.13). Longer time using 4DFlow CMR at our centre was associated with success; in children, older age was also associated with exam success. There was an about 12-month learning curve in children. The success rate was lowest in neonates. Inter-observer and intra-observer agreement were substantial. CONCLUSION: Our results suggest that 4DFlow CMR usually provides a comprehensive assessment of CHD in adults and children. A learning curve exists for children and the investigation remains challenging in neonates.
Subject(s)
Heart Defects, Congenital , Heart Septal Defects , Adolescent , Adult , Aged , Child , Child, Preschool , Heart , Heart Defects, Congenital/diagnostic imaging , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Young AdultABSTRACT
BACKGROUND: Transcatheter pulmonary valvuloplasty in neonates with pulmonary atresia and intact ventricular septum (PA-IVS) or duct-dependent pulmonary valve stenosis (DD-PVS) has become a reasonable alternative to surgical right ventricle decompression. AIM: To investigate mid-term outcomes following pulmonary valvuloplasty. METHODS: Sixty-five neonates with PA-IVS (n=29) or DD-PVS (n=36) (median age 4 days; mean weight 3.0kg) undergoing pulmonary valvuloplasty were reviewed retrospectively. Procedural data and clinical outcomes were assessed. RESULTS: Pulmonary valvuloplasty was successful in 59 patients (90.8%). Preterm birth, larger tricuspid valve annulus diameter and PA-IVS correlated with procedural failure. Eleven patients (18.6%) required a Blalock-Taussig shunt during early follow-up, despite valvuloplasty. These neonates had smaller tricuspid and pulmonary valve annulus Z-scores (-1.9 vs. -0.8 [p=0.04] and -2.5 vs. -0.9 [P=0.005], respectively) and a higher incidence of "bipartite" right ventricle (P=0.02). Mean follow-up was 5.4±3.3 years. Mortality after successful valvuloplasty was 8.5% (n=5). Among the 54 survivors, biventricular repair was achieved in 52 patients (96.3%), including nine with a previous Blalock-Taussig shunt. The cumulative rate of subsequent surgery (excluding Blalock-Taussig shunt) was 13.7% (95% confidence interval 6.8-26.7%) and 16.4% (95% confidence interval 8.5-30.4%) at 2 and 4 years, respectively. Secondary surgery was significantly more frequent in PA-IVS compared with DD-PVS, and in neonates with a Blalock-Taussig shunt (P=0.003 and 0.01, respectively). CONCLUSIONS: Selected neonates with DD-PVS or PA-IVS managed by transcatheter pulmonary valvuloplasty had a good mid-term outcome. In neonates with a borderline small right ventricle, a hybrid strategy with a supplementary source of pulmonary blood flow can be efficient to achieve biventricular repair.
Subject(s)
Balloon Valvuloplasty/methods , Cardiac Catheterization/methods , Heart Defects, Congenital/therapy , Pulmonary Atresia/therapy , Pulmonary Valve/abnormalities , Age Factors , Balloon Valvuloplasty/adverse effects , Balloon Valvuloplasty/mortality , Cardiac Catheterization/adverse effects , Cardiac Catheterization/mortality , Databases, Factual , Female , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/mortality , Heart Defects, Congenital/physiopathology , Hemodynamics , Humans , Infant, Newborn , Male , Pulmonary Atresia/diagnostic imaging , Pulmonary Atresia/mortality , Pulmonary Atresia/physiopathology , Pulmonary Circulation , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/physiopathology , Recovery of Function , Retrospective Studies , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: We sought to describe early and late outcomes in a large surgical series of patients with anomalous aortic origin of coronary arteries. METHODS: We performed a retrospective multicentre study including surgical patients with anomalous aortic origin of coronary arteries since 1991. Patients with isolated high coronary takeoff and associated major congenital heart disease were excluded. RESULTS: We collected 156 surgical patients (median age 39.5 years, interquartile range 15-53) affected by anomalous right (67.9%), anomalous left (22.4%) and other anatomical abnormalities (9.6%). An interarterial course occurred in 86.5%, an intramural course in 62.8% and symptoms in 85.9%. The operations included coronary unroofing (56.4%), reimplantation (19.2%), coronary bypass graft (15.4%) and other (9.0%). Two patients with preoperative cardiac failure died postoperatively (1.3%). All survivors were discharged home in good clinical condition. At a median follow-up of 2 years (interquartile range 1-5, 88.5% complete), there were 3 deaths (2.2%), 9 reinterventions in 8 patients (5 interventional, 3 surgical); 91.2% are in New York Heart Association functional class ≤ II, but symptoms persisted in 14.2%; 48.1% of them returned to sport activity. On Kaplan-Meier analysis, event-free survival at follow-up was 74.6%. Morbidity was not significantly different among age classes, anatomical variants and types of surgical procedures. Furthermore, return to sport activity was significantly higher in younger patients who participated in sports preoperatively. CONCLUSIONS: Surgical repair of anomalous aortic origin of coronary arteries is effective and has few complications. Unroofing and coronary reimplantation are safe and are the most common procedures. The occurrence of late adverse events is not negligible, and long-term surveillance is mandatory. Most young athletes can return to an unrestrained lifestyle.
Subject(s)
Abnormalities, Multiple/surgery , Aorta, Thoracic/abnormalities , Aorta, Thoracic/surgery , Coronary Vessel Anomalies/surgery , Adolescent , Adult , Cardiology , Europe , Female , Humans , Male , Middle Aged , Retrospective Studies , Societies, Medical , Time Factors , Treatment Outcome , Vascular Surgical Procedures/methods , Young AdultABSTRACT
BACKGROUND: Anomalous aortic origin of coronary arteries (AAOCA) is a rare abnormality, whose optimal management is still undefined. We describe early outcomes in patients treated with different management strategies. METHODS: This is a retrospective clinical multicenter study including patients with AAOCA, undergoing or not surgical treatment. Patients with isolated high coronary take off and associated major congenital heart disease were excluded. Preoperative, intraoperative, anatomical and postoperative data were retrieved from a common database. RESULTS: Among 217 patients, 156 underwent Surgical repair (median age 39â¯years, IQR: 15-53), while 61 were Medical (median age 15â¯years, IQR: 8-52), in whom AAOCA was incidentally diagnosed during screening or clinical evaluations. Surgical patients were more often symptomatic when compared to medical ones (87.2% vs 44.3%, pâ¯<â¯0.001). Coronary unroofing was the most frequent procedure (56.4%). Operative mortality was 1.3% (2 patients with preoperative severe heart failure). At a median follow up of 18â¯months (range 0.1-23â¯years), 89.9% of survivors are in NYHAâ¯≤â¯II, while only 3 elderly surgical patients died late. Return to sport activity was significantly higher in Surgical patients (48.1% vs 18.2%, pâ¯<â¯0.001). CONCLUSIONS: Surgery for AAOCA is safe and with low morbidity. When compared to Medical patients, who remain on exercise restriction and medical therapy, surgical patients have a benefit in terms of symptoms and return to normal life. Since the long term-risk of sudden cardiac death is still unknown, we currently recommend accurate long term surveillance in all patients with AAOCA.
Subject(s)
Coronary Vessel Anomalies/diagnosis , Coronary Vessel Anomalies/therapy , Disease Management , Internationality , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
Thymic epithelial cells are one of the main components of the thymic microenvironment required for T-cell development. In this work, we describe an efficient method free of enzymatic and Facs-sorted methods to culture human medullary thymic epithelial cells without affecting the cell phenotypic, physiologic and functional features. Human medulla thymic epithelial cells (mTECs) are obtained by culturing thymic biopsies explants. After 7 days of primo-culture, mTECs keep their ability to express key molecules involved in immune tolerance processes such as autoimmune regulator, tissue-specific antigens, chemokines, and cytokines. In addition, the cells sensor their cultured environment and consequently adjust their gene expression network. Therefore, we describe and provide a human mTEC model that may be used to test the effect of various molecules on thymic epithelial cell homeostasis and physiology. This method should allow the investigations of the specificities and the knowledge of human mTECs in normal or pathological conditions and therefore discontinue the extrapolations done on the murine models.
ABSTRACT
OBJECTIVES: Adults with congenital heart disease in need of heart surgery frequently present with significant comorbidity. Furthermore, additional technical difficulties often related to redo operations increase the risk for postoperative mortality and morbidity. Hence, next to the type of the procedure, additional procedure-dependent and procedure-independent factors have to be considered for risk evaluation. The recently proposed grown-ups with congenital heart disease (GUCH) mortality and morbidity scores account for these additional risk factors. We sought to validate their predictive power in a large population operated in a single centre. METHODS: Data of all consecutive patients aged 18 years or more, who underwent surgery for congenital heart disease between 2005 and 2016, were collected. Mortality was defined as hospital mortality or mortality within 30 days following surgery. Morbidity was defined as occurrence of one or more of the following complications: renal failure requiring dialysis, neurologic deficit persisting at discharge, atrioventricular block requiring permanent pacemaker implantation, mechanical circulatory support, phrenic nerve injury and unplanned reoperation. The discriminatory power of the GUCH scores was assessed using the area under the receiver operating characteristics curve (c-index, including 95% CI). RESULTS: Eight hundred and twenty-four operations were evaluated. Additional procedure-dependent and procedure-independent factors, as defined in the GUCH scores, were present in 165 patients (20.0%) and 544 patients (66.0%), respectively. Hospital mortality and morbidity was 3.4% and 10.0%, respectively. C-index for GUCH mortality score was 0.809 (0.742-0.877). C-index for GUCH morbidity score was 0.676 (0.619-0.734). CONCLUSIONS: We could confirm the good predictive power of the GUCH mortality score for postoperative mortality in a large population of adults with congenital heart disease.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Decision Support Techniques , Heart Defects, Congenital/surgery , Adolescent , Adult , Age Factors , Aged , Cardiac Surgical Procedures/mortality , Comorbidity , Female , France/epidemiology , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/mortality , Hospital Mortality , Humans , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young AdultABSTRACT
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ABSTRACT
BACKGROUND: The adult congenital heart surgery (ACHS) score was derived from The Society of Thoracic Surgeons Congenital Heart Surgery Database. The score was validated with data for 1,603 operations and reached a good predictive power. We sought to evaluate its predictive power for 1,654 operations performed in two European centers. METHODS: Data of all consecutive patients aged 18 years or more who underwent surgery for congenital heart disease between 2004 and 2013 at center 1 (n = 830) and between 2005 and 2016 at center 2 (n = 824) were collected. Mortality was defined as hospital mortality or mortality within 30 days after surgery. The discriminatory power of the ACHS score was assessed using the area under the receiver-operating characteristics curve (c-index). RESULTS: During the examined 13-year period, 1,639 operations of 43 different procedural groups were eligible for scoring. The most frequent procedures were closure of atrial septal defect (n = 175, 10.7%), repair of partial anomalous pulmonary venous connection (n = 117, 7.1%), and aortic valve replacement (n = 112, 6.8%). Hospital mortality was 3.1%. The procedures with the highest mortality were heart transplantation (3 of 11, 27.3%), mitral valve replacement (9 of 39, 23.1%), and systemic venous stenosis repair (2 of 9, 22.2%). The c-index for the ACHS mortality score was 0.760 (0.750 in center 1 and 0.772 in center 2). CONCLUSIONS: The ACHS score reached similar, good predictive power in two different centers. The score is a useful tool to analyze surgical outcomes and to support individual decision making.