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Supraventricular tachyarrhythmias pose a significant challenge in neonates and infants, particularly within the first year of life, where prompt and effective management is crucial. By synthesizing available evidence and clinical experience, this review aims to provide a comprehensive overview of antiarrhythmic therapy in this vulnerable population, with a focus on narrow QRS supraventricular tachyarrhythmias. This review examines the current understanding of supraventricular tachyarrhythmia management and discusses the challenges associated with antiarrhythmic therapy in newborns and infants during the critical first year of life, evaluating the efficacy and safety of various antiarrhythmic agents commonly utilized in this population, including dosing considerations, adverse effects, and strategies for acute management and prophylactic long-term antiarrhythmic treatment.

Background: Wearable cardioverter-defibrillators (WCDs) are currently used in patients at temporarily heightened risk for sudden cardiac death (SCD) who are temporarily unable to receive an implantable cardioverter-defibrillator (ICD). WCD can safely record and terminate life-threatening arrhythmias through a non-invasive electrode-based system. The current clinical indications for WCD use are varied and keep evolving as experience with this technology increases. Methods: We reviewed and explored the data behind indications for WCD use and discuss its usefulness in congenital heart disease (CHD) patients. Results: We considered 8 consecutive patients (mean age 35.25 years, range 18–51 years, average duration of WCD use 4 months, range 3–6 months) with complex CHD, in which a WCD was used between June 2018 and January 2022. No sustained ventricular arrhythmias requiring shocks were recorded in the observation period. No inappropriate shocks were recorded. All the patients showed a good compliance and a very high mean wear time per day (21.2 ± 1 h a day). Four patients implanted a permanent device (3 CRT-D, 1 ICD), three underwent cardiac surgery at the end of the WCD period and one is still on the waiting list for the operation. Conclusions: Larger trial could confirm the possible conceivable benefit from an extended use of the WCD in certain populations with complex CHD as in our case series, especially in patients with life-treating ventricular arrhythmias waiting for surgery for residual cardiac defects or in the early phases following the surgical/hemodynamic interventions, patients with tachycardiomyopathy expected to improve after the arrhythmias are removed and patients awaiting implantation of an ICD at high risk due to active infection.

Obstruction of the superior vena cava represents an under-recognized cause of chylothorax in the adult population. Our case report describes the successful conservative management of chylothorax due to bilateral superior vena cava obstruction in an adult patient with complex congenital heart disease. (Level of Difficulty: Beginner.)

Background: real-world data on COVID-19 vaccine safety, immunogenicity and acceptance in adults with congenital heart disease (ACHD) are lacking. Methods: ACHD patients who were offered COVID-19 vaccination from January to June 2021 were included. Data on adverse events, on patients’ attitude towards vaccination and antispike IgG titre were retrospectively collected. A group of healthy individuals with similar age and sex undergoing vaccination was included for comparison. Results: 208 patients followed in a single ACHD tertiary centre (33.3 [26–45] years, 54% male) received COVID-19 vaccine, 65% vaccinated at our institution: 199 (96%) received Pfizer–BioNTech BNT162b2 vaccine, 4 (2%) Moderna-1273 and 5 (2%) AstraZeneca–ChAdOx1. Median follow-up after vaccination was 79 [57–96] days. No major adverse event was reported and the incidence of minor events was not different between ACHD patients and the control group. One patient was diagnosed with acute pericarditis. There were two deaths unrelated to the vaccine during follow-up. Three (1.5%) vaccinated patients tested positive for COVID-19. Antispike IgG titre, available in 159 (76%) patients, was 1334 [600–3401] BAU/ml, not significantly different from the control group (p=0.2). One patient with Fontan failure was seronegative. Advanced physiological stage was associated with lower antibody response, independently from previous viral exposure (p

Background: Implantable cardioverter defibrillators (ICD) are widely accepted therapy in congenital heart disease (CHD) patients at risk of life-threatening ventricular arrhythmias or sudden cardiac death (SCD). Initial experience with subcutaneous ICD (S-ICD) systems has shown a high efficacy. However, the use of S-ICD in complex ACHD (adult congenital heart disease) implies some specific considerations, as the safety for these patients in unknown and recommendations among physicians may vary widely. Methods: We review the data and studied the indications for S-ICD in complex ACHD and discuss its usefulness in clinical practice. Results: From a large cohort of 297 patients enrolled in the S-ICD “Monaldi care” registry, that encompass all the patients implanted in the Monaldi Hospital of Naples, we considered 14 consecutive complex ACHD patients (aged 35.9 ± 16.7 years) who underwent S-ICD implant from February 2015 to June 2020. Mean follow-up was 23 ± 19.5 months. All the patients showed a good compliance to the device system with no complications (infections or skin erosions). Four patients (1 M/3F aged 38.2 ± 11.3) were listed for heart transplantation (HTX). Two of these underwent HTX, one died for refractory heart failure (HF) and one is still on the waiting list. Conclusions: There might be a conceivable benefit from an extended use of the S-ICD in selected patients with CHD, especially in those with life-treating ventricular arrhythmias and complex anatomy or patients awaiting HTX. S-ICD appears to be a safe alternative to a transvenous system when a transvenous ICD cannot be implanted and pacing is not required.

Background Allergic sensitization in children and allergic diseases arising therefrom are increasing for decades. Several interventions, functional foods, pro- and prebiotics, vitamins are proposed for the prevention of allergies and they can’t be uncritically adopted.Objective This Consensus document was developed by the Italian Society of Preventive and Social Paediatrics and the Italian Society of Paediatric Allergy and Immunology.The aim is to provide updated recommendations regarding allergy prevention in children.Methods The document has been issued by a multidisciplinary expert panel and it is intended to be mainly directed to primary care paediatricians.It includes 19 questions which have been preliminarily considered relevant by the panel. Relatively to each question, a literature search has been performed, according to the Italian National Guideline Program. Methodology, and a brief summary of the available literature data, has been provided.Many topics have been analyzed including the role of mother’s diet restriction, use of breast/formula/hydrolyzed milk; timing of introduction of complementary foods, role (if any) of probiotics, prebiotics, vitamins, exposure to dust mites, animals and to tobacco smoke.Results Some preventive interventions have a strong level of recommendation. (e.g., the dehumidifier to reduce exposure to mite allergens). With regard to other types of intervention, such as the use of partially and extensively hydrolyzed formulas, the document underlines the lack of evidence of effectiveness.No preventive effect of dietary supplementation with polyunsaturated fatty acids, vitamins or minerals has been demonstrated.There is no preventive effect of probiotics on asthma, rhinitis and allergic diseases. It has demonstrated a modest effect, but steady, in the prevention of atopic dermatitis.Conclusions The recommendations of the Consensus are based on a careful analysis of the evidence available.The lack of evidence of efficacy does not necessarily imply that some interventions may not be effective, but currently they can’t be recommended. Keywords: Allergy, Children, Prevention, Consensus

Background: Cystic fibrosis is the most common hereditary recessive disease with an incidence of about 1:2500/3000. It has long been known that the disease is caused by deleterious mutations in the CFTR gene. Conventionally, the disease is diagnosed in several phases. The analysis of all the possible disease-causing molecular alterations is time consuming and may not lead to a definitive diagnosis in several cases. Consequently, we propose, in this paper, a rapid sequencing method that, in a single procedural asset, reveals the presence of small mutations and also the copy number variants (CNVs) from the DNA extracted from the Guthrie Spot., Materials and Methods: We first sequenced 30 blood spots, then we validated the method on 100 spots that underwent both traditional analyses and this complete NGS sequencing, and lastly, we tested the strategy on patients who normally do not reach the molecular sequencing step because of low level of Immune-Reactive Trypsinogen., Results: Using this procedure, we identified 97 variants in the CFTR gene of our samples and 6 CNVs. Notably, the significant data were obtained in the group of patients with borderline or negative IRT who routinely would not undergo molecular testing. We also identified 6 carriers of "disease-causing" variants., Conclusion: This method is very robust. Indeed, there was a 100% concordance with Sanger sequencing validation, and 6 mutation carriers were identified who normally escaped molecular testing with actual conventional procedure. There were also 3 duplications of almost the entire gene in heterozygosity, which were not seen with traditional methods. Being quick and easy to perform, we suggest that complete sequencing of the CFTR gene, as in this study be considered for all newborns., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to evaluate the characteristics and outcome of patients undergoing ablation after electrical storm (ES)., Methods: Clinical and procedural characteristics, ventricular tachycardia (VT) recurrence, and mortality rates from 1940 patients undergoing VT ablation were compared between patients with and without ES., Results: The group of 677 patients with ES (34.9%) were older, were more frequently men, and had a lower ejection fraction, more advanced heart failure, and a higher prevalence of cardiovascular comorbidities as compared with those without ES (86.1% patients with ES had ≥2 comorbidities vs 71.4%; P < .001). Patients with ES had more inducible VTs (2.5 ± 1.8 vs 1.9 ± 1.9; P < .001), required longer procedures (296.1 ± 119.1 minutes vs 265.7 ± 110.3 minutes; P < .001), and had a higher in-hospital mortality (42 deaths [6.2%] vs 18 deaths [1.4%]; P < .001). At 1-year follow-up, patients with ES experienced a higher risk of VT recurrence and mortality (32.1% vs 22.6% and 20.1% vs 8.5%; long-rank, P < .001 for both). Among patients with ES, those without any inducible VT after ablation had a higher survival rate (86.3%) than did those with nonclinical VTs only (72.9%), those with clinical VTs inducible at programmed electrical stimulation (51.2%), and not-tested patients (65.0%) (long-rank, P < .001 for all). In multivariate analysis, ES remained an independent predictor of in-hospital mortality, VT recurrence, and 1-year mortality (P < .001)., Conclusion: Patients with ES have a high risk of VT recurrence and mortality. Patient and procedure characteristics are consistent with advanced cardiac disease and longer and more complex procedures. In patients with ES, acute procedural success is associated with a significant reduction in VT recurrence and improved 1-year survival., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Fluid challenge may help in the differential diagnosis between pre- and postcapillary pulmonary hypertension (PH). However, the test is still in need of standardization and better defined clinical relevance., Methods: Two hundred twelve patients referred for PH underwent a right-sided heart catheterization with measurements before and after rapid infusion of 7 mL/kg of saline. PH was defined as mean pulmonary artery pressure ≥ 25 mm Hg, and postcapillary PH was defined as pulmonary artery wedge pressure (PAWP) > 15 mm Hg. An increase in PAWP ≥ 18 mm Hg was considered diagnostic for postcapillary PH. At baseline, 66 patients received a diagnosis of no PH; 22, of postcapillary PH; and 124, of precapillary PH (mostly pulmonary arterial hypertension)., Results: After fluid challenge, five of 66 patients with no PH (8%) and eight of 124 with precapillary PH (6%) had the diagnosis reclassified as postcapillary PH. Fluid challenge was associated with an increase in PAWP by 7 ± 2 mm Hg in postcapillary PH and 3 ± 1 mm Hg in both precapillary PH and no-PH groups. Between-group differences were significant, but there was overlap. There were no adverse events related to fluid challenge. Prediction bands calculated from quadratic fits of the PAWP responses in pooled control subjects with no PH and patients with precapillary PH helped confirm 18 mm Hg as the cutoff for diagnosing postcapillary PH., Conclusions: Fluid challenge with 7 mL/kg saline increases PAWP, more in postcapillary than in precapillary PH or in control subjects with no PH. A cutoff value of 18 mm Hg allows reclassification of 6% to 8% of patients with precapillary PH or normal hemodynamic characteristics at baseline., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary arterial hypertension (PAH) after shunt closure is associated with a poor prognosis. The aim of this study was to assess retrospectively the hemodynamics of patients developing PAH after shunt closure., Methods: Hemodynamic data obtained by right heart catheterization (RHC) performed at baseline and after shunt closure were analyzed., Results: Twenty-two patients, 13 with atrial septal defect (ASD), 6 with ventricular septal defect (VSD), 1 with patent ductus arteriosus, 1 with both ASD and VSD, and 1 with complete atrio-ventricular canal have been considered. The mean age at closure was 25.3±20.1 years (range of 3 months to 56.7 years), and the mean age at PAH diagnosis was 37.0±20.8 years (range of 5 to 61.2 years). The time delay between shunt closure and PAH diagnosis was 140.2±100.2 months. At baseline RHC, hemodynamic data were as follows: pulmonary vascular resistance (PVR) of 8.6±2.6 Wood units, PVR index (PVRi) of 10.1±2.7 Wood units∗m(2), mean pulmonary arterial pressure of 43.7±9.7 mmHg, PVR to systemic vascular resistance ratio (PVR/SVR) of 0.70±0.23, and Qp/Qs of 1.6±0.4. In particular, 18/22 (81%) had PVR≥5 Wood units, 21/22 (95%) PVRi≥6 Wood units∗m(2), 21/22 (95%) PVR/SVR≥0.33, and 11/22 (50%) Qp/Qs≤1.5. During the follow-up, 5/22 (22%) patients died and one patient underwent successful double lung transplantation., Conclusions: High baseline values of PVR (≥5 Wood units), PVRi (≥6 Wood units∗m(2)) and PVR/SVR (≥0.33) are common findings in patients who develop PAH late after shunt closure. Large prospective clinical trials are needed to establish the safe limits for shunt closure., (© 2013.)

Background: Echocardiographic studies have contributed to progress in the understanding of the pathophysiology of the pulmonary circulation and have been shown to be useful for screening for and prognostication of pulmonary hypertension, but are considered unreliable for the diagnosis of pulmonary hypertension. We explored this apparent paradox with rigorous Bland and Altman analysis of the accuracy and the precision of measurements collected in a large patient population., Methods: A total of 161 patients referred for a suspicion of pulmonary hypertension were prospectively evaluated by a Doppler echocardiography performed by dedicated cardiologists within 1 h of an indicated right heart catheterization., Results: Nine of the patients (6%) were excluded due to an insufficient signal quality. Of the remaining 152 patients, 10 (7%) had no pulmonary hypertension and most others had either pulmonary arterial hypertension (36%) or pulmonary venous hypertension (40%) of variable severities. Mean pulmonary artery pressure, left atrial pressure and cardiac output were nearly identical at echocardiography and catheterization, with no bias and tight confidence intervals, respectively ± 3 mm Hg, ± 5 mm Hg and ± 0.3 L/min. However, the ± 2SD limits of agreement were respectively of + 19 and - 18 mm Hg for mean pulmonary artery pressure, + 8 and - 12 mm Hg for left atrial pressure and + 1.8 and - 1.7 L/min for cardiac output., Conclusions: Doppler echocardiography allows for accurate measurements of the pulmonary circulation, but with moderate precision, which explains why the procedure is valid for population studies but cannot be used for the individual diagnosis of pulmonary hypertension., (© 2013.)

Background: Oral bosentan is effective in pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). In patients with Down's syndrome, the effect of bosentan is largely unknown. Aim of the study was to evaluate the long-term effects of bosentan in adult patients with CHD-related PAH with and without Down's syndrome., Methods: WHO functional class, resting oxygen saturation, 6-minute walk test (6 MWT) and hemodynamics were assessed at baseline and after 12 months of bosentan therapy in patients with CHD-related PAH with and without Down's syndrome., Results: Seventy-four consecutive patients were enrolled: 18 with and 56 without Down's syndrome. After 12 months of bosentan therapy, both with and without Down's syndrome patients showed an improvement in WHO functional class (Down: 2.5 ± 0.5 vs 2.9 ± 0.6, p=0.005; controls: 2.5 ± 0.5 vs 2.9 ± 0.5, p=0.000002), 6-minute walk distance (Down: 288 ± 71 vs 239 ± 74 m, p=0.0007; controls: 389 ± 80 vs 343 ± 86 m, p=0.00003), and hemodynamics (pulmonary flow, Down: 4.0 ± 1.6 vs 3.5 ± 1.4 l/m/m(2), p=0.006; controls: 3.5 ± 1.4 vs 2.8 ± 1.0 l/m/m(2), p=0.0005; pulmonary to systemic flow ratio, Down: 1.4 ± 0.7 vs 1.0 ± 0.4, p=0.003; controls: 1.1 ± 0.7 vs 0.9 ± 0.3, p=0.012; pulmonary vascular resistance index, Down: 15 ± 9 vs 20 ± 13 WUm(2), p=0.007; controls: 2 0 ± 10 vs 26 ± 15 WUm(2), p=0.002). No differences in the efficacy of therapy were observed between the two groups., Conclusions: Bosentan was safe and well tolerated in adult patients with CHD-related PAH with and without Down's syndrome during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary hemodynamics improved, regardless of the presence of Down's syndrome., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of the present study was to evaluate the safety, tolerability, clinical and haemodynamic impact of add-on sildenafil in patients with congenital heart disease (CHD)-related pulmonary arterial hypertension (PAH) and Eisenmenger physiology after failure of oral bosentan therapy., Methods: Thirty-two patients with CHD-related PAH (14 male, mean age 37.1 ± 13.7 years) treated with oral bosentan underwent right heart catheterization (RHC) for clinical worsening. After RHC, all patients received oral sildenafil 20mg thrice daily in addition to bosentan. Clinical status, resting transcutaneous oxygen saturation (SpO(2)), 6-minute walk test (6MWT), serology and RHC were assessed at baseline (before add-on sildenafil) and after 6 months of combination therapy., Results: Twelve patients had ventricular septal defect, 8 atrio-ventricular canal, 6 single ventricle, and 6 atrial septal defect. Twenty-eight/32 had Eisenmenger physiology and 4 (all with atrial septal defect) did not. All patients well tolerated combination therapy. After 6 months of therapy, an improvement in clinical status (WHO functional class 2.1 ± 0.4 vs 2.9 ± 0.3; P=0.042), 6-minute walk distance (360 ± 51 vs 293 ± 68 m; P=0.005), SpO(2) at the end of the 6MWT (72 ± 10 vs 63 ± 15%; P=0.047), Borg score (2.9 ± 1.5 vs 4.4 ± 2.3; P=0.036), serology (pro-brain natriuretic peptide 303 ± 366 vs 760 ± 943 pg/ml; P=0.008) and haemodynamics (pulmonary blood flow 3.4 ± 1.0 vs 3.1 ± 1.2l/min/m(2), P=0.002; pulmonary vascular resistances index 19 ± 9 vs 24 ± 16 WU/m(2), P=0.003) was observed., Conclusions: Addition of sildenafil in adult patients with CHD-related PAH and Eisenmenger syndrome after oral bosentan therapy failure is safe and well tolerated at 6-month follow-up, resulting in a significant improvement in clinical status, effort SpO(2), exercise tolerance and haemodynamics., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Fas (CD95) is a transmembrane molecule that induces programmed cell death (PCD) of lymphocytes. We examined its function in children with chronic thrombocytopenia, serum autoantibodies, and lymphadenopathy and/or splenomegaly. We found that T-cell lines from six of seven patients with this autoimmune/lymphoproliferative disease (ALD) were relatively resistant to PCD induced by monoclonal antibodies to Fas. By contrast, Fas function was normal in control patients with typical chronic idiopathic thrombocytopenic purpura (ITP) without lymphadenopathy. The defect was not due to decreased Fas expression, nor to over-production of soluble forms of Fas. Moreover, it specifically involved the Fas system because PCD was induced in the normal way by methylprednisolone. Complementary DNA sequencing of the Fas gene did not identify any causal mutation in patients with ALD. This distinguished them from patients with the human autoimmune lymphoproliferative syndrome (ALPS), who carry mutations of the Fas gene. Moreover, patients with ALD did not show the peripheral expansion of CD4/CD8 double-negative T cells that characterizes the ALPS phenotype. Fas signaling involves activation of a sphingomyelinase-catalyzing production of ceramide. We found that ceramide-induced PCD was defective in patients with ALD and not in patients with typical chronic ITP. These data suggest that the ALD patient defect involves the Fas signaling pathway downstream from the sphingomyelinase and that Fas gene mutations and double-negative T-cell expansion are not the only signs of a defective Fas system.

Programmed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30).

The relationships among hemoglobin concentration (Hb), red cell 2,3-diphosphoglycerate (2,3-DPG), and p50 were studied in 20 chronically hypertransfused patients with thalassemia major. In the nontransfused control group, which included normal individuals as well as patients with sickle cell disease or iron deficiency anemia, the Hb correlated inversely with both 2,3-DPG concentration and p50, as is well established. In contrast, however, prior to transfusion, at the nadir of Hb, patients with thalassemia major had inappropriately low 2,3-DPG concentrations and p50s. These findings occurred in all patients, regardless of whether they had received packed, leukocyte-poor, or frozen-thawed red cells. The hypothesis that the time of blood storage was a factor was excluded by repeatedly transfusing one patient with packed red cells administered within 4 hr of collection in CPDA-1. A second hypothesis, that red cell function might be impaired by the iron-overloaded thalassemic environment, was excluded by studying a newly diagnosed, newly transfused patient with aplastic anemia. In both cases, the same inability to appropriately increase 2,3-DPG and p50 as the Hb fell during the intertransfusion interval was noticed. These data suggest that red cells of chronically transfused patients are unable to adapt to the decline in Hb that occurs during the intertransfusion interval.