Long-term incidence of arrhythmias in extracardiac conduit Fontan and comparison between systemic left and right ventricle.

AIMS: The extracardiac conduit-Fontan (ECC) has become the preferred technique for univentricular heart palliation, but there are currently no data on the incidence of long-term arrhythmias. This study investigated the incidence of arrhythmias and relation to single ventricle morphology in the long-term follow-up (FU) in ECC. METHODS AND RESULTS: All patients with ECC performed in our Centre between 1987 and 2017 were included (minimum FU 5 years). Of 353 consecutive patients, 303 [57.8% males, aging 8-50 (median 20) years at last FU] were considered and divided into two groups depending on left (194 in Group 1) or right (109 in Group 2) ventricular morphology. Eighty-five (28%) experienced ≥1 arrhythmic complications, with early and late arrhythmias in 17 (5.6%) and 73 (24.1%) patients, respectively. Notably, late bradyarrhythmias occurred after 6 years in 21 (11%) patients in Group 1, and in 15 (13.8%) in Group 2 [P = 0.48]. Late tachyarrhythmias occurred in 55 (18.2%) patients after 12 years: 33 (17%) in Group 1 and 22 (20.2%) patients in Group 2 [P  = 0.5]. Ventricular tachycardias (VT) were documented after 12.5 years in 14 (7.2%) patients of Group 1 and 15 (13.8%) of Group 2 [P = 0.06] with a higher incidence in Group 2 during the FU [P = 0.005]. CONCLUSION: Extracardiac conduit is related to a significant arrhythmic risk in the long-term FU, higher than previously reported. Bradyarrhythmias occur earlier but are less frequent than tachyarrhythmias. Interestingly, patients with systemic right ventricle have a significantly higher incidence of VT, especially in a very long FU.

Corrigendum: Case Report: Epstein-Barr virus and constrictive pericarditis-an unusual combination.

[This corrects the article DOI: 10.3389/fped.2023.1215928.].

Double-Outlet Left Ventricle: Case Series and Systematic Review of the Literature.

Double-outlet left ventricle (DOLV) is an abnormal ventriculo-arterial connection characterized by the origin of both great arteries from the morphological left ventricle. The aim of our paper is to describe the morphological and imaging features of DOLV and to assess the prevalence of the associated malformations and their surgical outcomes. METHODS From 2011 to 2022, we retrospectively reviewed the electronic case records of patients diagnosed with DOLV at the Bambino Gesu Children's Hospital. A systematic search was developed in MEDLINE, Web of Science, and EMBASE databases to identify reports assessing the morphology and outcomes of DOLV between 1975 and 2023. RESULTS: Over a median follow-up of 9.9 years (IQR 7.8-11.7 y), four cases of DOLV were identified at our institution. Two patients were diagnosed with (S,D,D) DOLV subaortic VSD and pulmonary stenosis (PS): one patient had (S,D,D) DOLV with doubly committed VSD and hypoplastic right ventricle, and another patient had (S,D,L) DOLV with subaortic VSD and PS (malposition type). Pulmonary stenosis was the most commonly associated lesion (75%). LITERATURE REVIEW: After systematic evaluation, a total of 12 reports fulfilled the eligibility criteria and were included in our analysis. PS or right ventricular outflow tract obstruction was the most commonly associated lesion (69%, 95% CI 62-76%). The most common locations of VSD were subaortic (pooled prevalence: 75%, 95% CI 68-81), subpulmonary (15%, 95% CI 10-21), and doubly committed (7%, 95% CI 4-12). The position of the great arteries showed that d-transposition of the aorta was present in 128 cases (59% 95% CI 42-74), and l-transposition was present in 77 cases (35%, 95% CI 29-43).

Pediatric airway compression in aortic arch malformations: a multidisciplinary approach.

Background: Aortic arch malformations (AAMs) should be suspected in the presence of persistent respiratory symptoms despite medical treatment or feeding problems at the pediatric age. Aim: We report a descriptive cohort of patients with AAMs and the local management protocol applied. Methods: A total of 59 patients with AAM were retrospectively reviewed. Three groups were identified: double aortic arch (DAA), group 1; complete vascular ring (non-DAA), group 2; and anomalous origin of the innominate artery (IA), group 3. Results: Prenatal diagnosis was available for 62.7% of the patients. In all, 49.2% of children were symptomatic. There was a significantly different prevalence of respiratory symptoms within the three groups: 73.7% in group 1, 24.2% in group 2, and 100% in group 3 (p-value: <0.001). Surgery was considered in the presence of symptoms in patients with DAA and in those with reduction of the tracheal section area greater than 50%. A total of 52.5% of the patients underwent surgical repair (median age 6 months). The median follow-up interval was 21.9 months. Respiratory symptoms improved in most symptomatic patients. Conclusions: No specific protocols are available for the management of patients with AAMs. Conservative treatment seems to be reasonable for asymptomatic patients or those with airway stenosis less than 50%. A close follow-up is necessary to identify early patients who become symptomatic.

Case report: Epstein-Barr virus and constrictive pericarditis-An unusual combination.

Constrictive pericarditis is a chronic inflammatory process that can lead to heart failure if not diagnosed and treated correctly. Although Epstein-Barr virus (EBV)-related pericarditis is a very rare condition, it should still be considered for a differential diagnosis. We report the case of an 18-year-old male, who was surgically treated for constrictive pericarditis, in which in situ hybridization to Epstein-Barr virus-encoded RNA (EBER) probe of the excised pericardium led to the subsequent etiological diagnosis of chronic pericarditis caused by EBV.

Late outcome of extracardiac Fontan patients: 32 years of follow-up.

OBJECTIVES: We sought to evaluate the long-term survival and risk factors for morbidity and mortality in our cohort of patients after extracardiac (EC) Fontan. METHODS: We collected and analysed follow-up data until September 2020 for all patients who underwent EC Fontan operation at our institution from November 1988 to November 2015. RESULTS: Out of 406 patients treated with EC Fontan at a mean age of 5.4 ± 4.5 years, 372 (91.6%) were discharged home; 15% were lost to follow-up. The median follow-up was 14.6 years (interquartile range 8.7-20.3). Two hundred patients (54%) had a good long-term outcome, with an event-free long-term survival, but late adverse events of any kind needing interventional or surgical reoperations were reported in 128 patients (34%). Forty-four patients (12%) developed late Fontan failure. Thirty-seven survivors (10%) had late arrhythmias, with the need for pacemaker implantation. Obstruction of the cavopulmonary pathway occurred in 49 patients (13%), but just 8 patients needed conduit surgical replacement. At 32 years, the survival probability was 84%. The risk of orthotopic heart transplant, considering death as a competing event (showed as cumulative incidence), was 12.5%. A preoperative diagnosis of hypoplastic left heart syndrome was an independent risk factor for the need for heart transplant. CONCLUSIONS: The EC Fontan shows satisfactory long-term survival and low incidence of adverse events and late failure. Conduit replacement is rare, and its longevity may not represent a substantial issue in these patients. However, as with other technical variants, the need for reoperations during long-term follow-up is a significant challenge.

Pediatric aortic valve neocuspidization.

Treatment of pediatric aortic valve disease is controversial. In this regard, interest is growing in the neocuspidization of the aortic valve according to Ozaki. In this video tutorial, we illustrate briefly the entire reconstruction technique of a neoaortic valve with pretreated autologous pericardium used in our institution in pediatric patients by describing a case of an incompetent native tricuspid aortic valve.

The Modern Surgical Approach to Pulmonary Atresia with Ventricular Septal Defect and Major Aortopulmonary Collateral Arteries.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals is a complex congenital heart defect that includes a heterogeneous subgroup of patients. Variation in the sources of pulmonary blood flow contributes to the complexity of the lesion and the diversity of approaches to its management. Unifocalization and rehabilitation focus on mobilization of collateral arteries and growth of native pulmonary arteries, respectively, with the ultimate surgical goal of achieving separated systemic and pulmonary circulations with the lowest possible right ventricular pressure. Regardless of the strategy, outcomes have altered the natural history of the disease, with a complete repair rate of approximately 80% and low early and late mortality rates. Given this heterogeneity of pulmonary vasculature, a tailored approach should be adopted for each patient, using all diagnostic methods currently offered by technical developments.

Blood flow characteristics after aortic valve neocuspidization in paediatric patients: a comparison with the Ross procedure.

AIMS: The aortic valve (AV) neocuspidization (Ozaki procedure) is a novel surgical technique for AV disease that preserves the natural motion and cardiodynamics of the aortic root. In this study, we sought to evaluate, by 4D-flow magnetic resonance imaging, the aortic blood flow characteristics after AV neocuspidization in paediatric patients. METHODS AND RESULTS: Aortic root and ascending aorta haemodynamics were evaluated in a population of patients treated with the Ozaki procedure; results were compared with those of a group of patients operated with the Ross technique. Cardiovascular magnetic resonance studies were performed at 1.5 T using a 4D flow-sensitive sequence acquired with retrospective electrocardiogram-gating and respiratory navigator. Post-processing of 4D-flow analysis was performed to calculate flow eccentricity and wall shear stress. Twenty children were included in this study, 10 after Ozaki and 10 after Ross procedure. Median age at surgery was 10.7 years (range 3.9-16.5 years). No significant differences were observed in wall shear stress values measured at the level of the proximal ascending aorta between the two groups. The analysis of flow patterns showed no clear association between eccentric flow and the procedure performed. The Ozaki group showed just a slightly increased transvalvular maximum velocity. CONCLUSION: Proximal aorta flow dynamics of children treated with the Ozaki and the Ross procedure are comparable. Similarly to the Ross, Ozaki technique restores a physiological laminar flow pattern in the short-term follow-up, with the advantage of not inducing a bivalvular disease, although further studies are warranted to evaluate its long-term results.

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot.

AIM: This study evaluates the risk factors associated with right ventricular (RV) dilation and dysfunction leading to pulmonary valve replacement (PVR) or adverse cardiac events in repaired Tetralogy of Fallot (rToF) patients. METHODS: Data from all rToF patients who underwent magnetic resonance imaging (MRI) evaluation at our hospital between February 2007 and September 2020 were collected. RESULTS: Three hundred and forty-two patients (60% males, 42% older than 18 years), with a median age of 16 years (IQR 13-24) at the time of MRI, were included. All patients underwent complete repair at a median age of 8 months (IQR 5-16), while palliation was performed in 56 patients (16%). One hundred and forty-four patients (42%) subsequently received pulmonary valve replacement (PVR). At the multivariate analysis, male gender was an independent predictor for significant RV dilation, RV and left ventricular (LV) dysfunction. Transventricular ventricular septal defect (VSD) closure and previous palliation significantly affected LV function and RV size, respectively. Male gender and the transventricular VSD closure were independent predictors for PVR. CONCLUSIONS: Male gender and surgical history (palliation, VSD closure approach) significantly affected the long-term outcomes in rToF patients and should be taken into consideration in the follow-up management and in PVR timing in this patient population.

Idiopathic Ventricular Fibrillation: Look for the Hidden Guilty-A case of aborted cardiac death.

We report a unique case of a 6-year-old male child with aborted sudden cardiac death due to ventricular fibrillation. A rare anomalous aortic origin of the right coronary artery was detected and supposed to be the cause of the malignant arrhythmia. Clinical exome sequencing did not reveal any pathogenic variant related to channelopathies nor other known heart-related genes. The patient underwent cardiac surgery and a cardiac defibrillator was implanted for secondary prevention.

Premature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients.

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to early thymic involution and immune dysregulation. Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in DS patients, normally seen in older healthy subjects. Moreover, our whole transcriptomic analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased ß-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere length and integrity markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. In conclusion, our findings support the key role of cellular senescence in the pathogenesis of immune defect in DS while adding new players, such as epigenetic regulation and increased oxidative stress, to the pathogenesis of immune dysregulation.

Predictors of survival in paediatric mitral valve replacement.

OBJECTIVES: The aim of this study was to identify the predictors of death and of reintervention after mitral valve replacement (MVR) in children. METHODS: A single-centre retrospective study was performed including 115 patients under the age of 18 undergoing MVR between 1982 and 2019. For all patients, the ratio of prosthetic valve size (diameter in mm) to weight (kg) at surgery was calculated and long-term result was assessed. The primary outcome was freedom from mitral valve (MV) re-replacement. The composite secondary outcome was freedom from death or transplant. RESULTS: Fifty-four patients had a previous surgical attempt to MV repair. The median age at surgery was 5.5 years (interquartile range 1.21-9.87). Death/transplant-free survival was 77 ± 4% at 5 years and 72 ± 5% at 10 years. Univariate analysis showed a size/weight ratio higher than 2 and age <2 years as significant risk factors for death or transplant. Freedom from MV re-replacement at 5 and 10 years was 90 ± 3% and 72 ± 6%, respectively. Biological prosthesis implanted at first replacement (P = 0.007) and size/weight ratio higher than 2 (P = 0.048) were predictors of reoperation. Significant upsizing (P < 0.0001) of mitral prosthesis was observed at re-replacement. CONCLUSIONS: MVR is a viable strategy in children with unrepairable MV disease. Mortality can be predicted based on size/weight ratio and age <2 years. MV re-replacement can be performed with low morbidity and mortality and a larger-size prosthesis can often be placed at the time of redo.

Aortic Valve Neocuspidalization May Be a Viable Alternative to Ross Operation in Pediatric Patients.

The aim of the study was to evaluate the medium-term results of aortic valve neocuspidalization according to Ozaki compared to Ross procedure for treatment of isolated aortic valve disease in pediatric age. Thirty-eight consecutive patients with congenital or acquired aortic valve disease underwent either Ozaki (n = 22) or Ross (n = 16) operation between 01/2015 and 05/2020. The primary outcome was progression of aortic valve disease and aortic ring and root dimension, whereas secondary outcome was freedom from reintervention or death by type of operation. Median age was 12.4 (8.8-15.8) years and the prevailing lesion was stenosis in 20 cases (52%) and incompetence in 18 (48%). One death occurred in the Ross group in the early postoperative period, while there were no deaths in the Ozaki group. Effective treatment of aortic valve stenosis or regurgitation occurred in both groups and remained stable over a median follow-up of 18.2 (5-32) months. In Ozaki group, 3 patients required aortic valve replacement at 4.9, 3.5, and 33 months, respectively. In Ross group, 1 patient required Melody pulmonary valve replacement, whereas none required aortic valve surgery. Finally, significantly higher aortic transvalvular gradient at follow-up was recorded in Ozaki group compared to Ross group. Overall, there was no significant difference in freedom from reoperation or death between the two groups. The medium-term outcome of Ozaki and Ross in pediatric patients is similar, despite an increased tendency of the former to develop aortic transvalvular gradient in the follow-up. Future larger multicenter studies with longer follow-up are warranted to confirm these results.

Aortic valve neocuspidalization in paediatric patients with isolated aortic valve disease: early experience.

OBJECTIVES: There is growing interest in the aortic valve (AV) neocuspidalization technique for the treatment of aortic valve disease (AVD). We report our medium-term results with this procedure performed in a paediatric patient population. METHODS: Between July 2016 and May 2020, 22 patients with both congenital and acquired isolated AVD were treated with neocuspidalization. The primary outcome was progression of the preoperatively assessed AVD in the immediate postoperative course and at follow-up. Secondary outcome was freedom from reintervention by material used. Potential predictors of failure were analysed in relation to the primary outcome. RESULTS: The median age at operation was 13.9 (interquartile range, 9.8-16.2) years, and the prevailing AV defect was stenosis in 10 cases (45%) and incompetence in 12 (55%). Pre-treated autologous pericardium was used in 13 patients whereas bovine pericardium in 9. Effective treatment of AV stenosis or regurgitation was achieved and remained stable over a median follow-up of 11.3 (4.7-21) months. Three patients required AV replacement at 4.9, 3.5 and 33 months. At follow-up, an upward trend of both median indexed vena contracta jet widths and aortic peak and mean gradients were recorded, the latter associated with a failure to grow the aortic annulus. Predictor of such outcome turned out to be the use of bovine pericardium. A significant inverse linear correlation between AV peak gradient at follow-up and preoperative aortic annular size (P = 0.008) was also demonstrated. CONCLUSIONS: The Ozaki procedure is safe and effective in paediatric patients with AV disease. The use of heterologous pericardium should probably be minimized. Moreover, preoperative small aortic annuli should probably be promptly treated by means of an associated ring enlargement procedure.

Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect.

Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single-center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all-cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan-Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients.

Recurrent Wheezing in Pre-school Age: Not Only Airway Reactivity!

Background: About a fifth of all mediastinal masses are primary cysts arising in the absence of other underlying pathology. Bronchogenic cysts, although rare, are the most frequent type responsible for lower airways compression as they often develop in the peripheral branches of the tracheobronchial tree. Case presentation: We report the case of a 6-months-old child admitted for acute respiratory distress and wheezing not responsive to asthma treatment. Digestive and airway endoscopy proved a mild and a marked reduction of the esophageal and tracheal lumen, respectively. The nocturnal polygraphy showed an underlying obstructive disorder and the chest CT scan confirmed the presence of a wide mediastinal cyst compressing the trachea. The mass, later identified as a bronchogenic cyst, was surgically removed with complete resolution of the patient's respiratory symptoms. Discussion: Our case shows that differential diagnosis of wheezing in pre-school aged children should encompass causes others than airway reactivity, thus prompting further evaluation and management.

Surgical Management of Fallot's Tetralogy With Pulmonary Atresia and Major Aortopulmonary Collateral Arteries: Multistage Versus One-Stage Repair.

A strict and rational approach to Fallot's tetralogy with pulmonary atresia and major aortopulmonary collateral arteries allows to achieve optimal results. Rehabilitative and unifocalization strategies do not constitute separate philosophies; instead the surgical strategy should be tailored to each individual patient. Based on our previous experience, the ability to achieve definitive intracardiac repair is the real determinant of both improved survival and adequate systolic right ventricular performance on mid-term follow-up.