Effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve-related aortopathy.

AIMS: The aim of this study is to evaluate the effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve (BAV)-related aortopathy and ascending phenotype. METHODS: Consecutive paediatric patients (≤16 years) with BAV and ascending aorta (AsAo) dilation (z-score > 3) were enrolled in this observational retrospective cohort study. Patients receiving prophylactic treatment with either atenolol (0.5 to 1.0 mg/kg/daily) or losartan (0.7 to 1.4 mg/kg/daily) were compared with those who did not receive medical prophylaxis (control group). The primary outcome of interest was the annual rate of change in maximal AsAo diameter z-score in the treatment and control groups. RESULTS: From a cohort of 1005 patients, 120 (mean age 11.3 ± 4.5 years, 82% males) fulfilled the inclusion criteria and were included in the study. Patients in the treatment and control group had similar age, sex, family history of BAV, BAV morphology, and baseline AsAo diameter. During a median follow-up of 7.1 years (interquartile range 3.8-10.2), no differences were observed in the annual growth rate of aortic diameter z-score between patients on treatment and controls. The prevalence of aortic diameter progression was similar in the treatment and control groups, and treatment with atenolol or losartan was not associated with a lower rate of aortic disease progression. CONCLUSIONS: The findings revealed no significant difference in the annual aortic growth rate between treated and untreated patients. Larger cohort studies or, ideally, randomized clinical controlled trials are needed to validate these findings.

Prevalence and Clinical Significance of Intraventricular Conduction Disturbances in Hospitalized Children.

Introduction: Data on the prevalence and clinical significance of interventricular conduction disturbances (IVCDs) in children are scarce. While incomplete right bundle branch blocks (IRBBBs) seem to be the most frequent and benign findings, complete bundle blocks and fascicular blocks are often seen in children with congenital/acquired cardiac conditions. This study aims to delineate the prevalence and the diagnostic accuracy of IVCD in children admitted to a paediatric cardiology unit. Methods: Children admitted to the paediatric cardiology unit between January 2010 and December 2020 who had an ECG were included in the study. IVCDs were diagnosed according to standard criteria adjusted for age. Results: Three thousand nine hundred and ninety-three patients were enrolled. The median age was 3.1 years (IQR: 0.0-9.2 years), and 52.7% were males. IVCDs were present in 22.5% of the population: 17.4% of the population presented with IRBBBs, 4.8% with a complete right bundle branch block (CRBBB), 0.1% with a complete left bundle branch block (CLBBB), 0.2% with a left anterior fascicular block (LAFB) and 0.2% with a combination of CRBBB and LAFB. Also, 26% of children with congenital heart disease had an IVCD, and 18% of children with an IVCD had previous cardiac surgery. The overall sensitivity of IVCD in detecting a cardiac abnormality was 22.2%, with a specificity of 75.5%, a PPV of 83.1% and an NPV of 15.1%, but the values were higher for CLBBB and LAFB. Conclusions: IVCDs were present in one-fifth of children admitted to the cardiology unit. IRBBB was the most frequent disturbance, while CRBBB, CLBBB and fascicular blocks were much rarer, though they had a higher predictive value for cardiac abnormalities.

Irrigated contact force sensing catheter for redo ablation of slow-fast atrioventricular nodal reentrant tachycardia in pediatric and adolescent patients: A case series.

Conventional nonirrigated catheters cannot be able to create adequate lesions for effective slow pathway modulation in certain cases of pediatric atrioventricular nodal reentrant tachycardia ablation. Irrigated contact force sensing catheters may be considered in pediatric and adolescent patients to obtain a more extensive slow pathway modulation for redo ablation, avoiding dangerous radiofrequency applications close to the compact atrioventricular node or complex left-sided procedures.

Contact allergy to subcutaneous implantable cardioverter defibrillator in a child with Brugada syndrome.

Allergic reactions to components of cardiac implantable electronic devices are rare and often go undiagnosed, which can lead to a misdiagnosis of device infection. Contact allergy to subcutaneous implantable cardioverter defibrillator (S-ICD) is extremely rare. In this report, we present a case of cobalt-related contact allergy in a pediatric patient with Brugada syndrome who underwent S-ICD implantation.

Left Ventricular Non-Compaction in Children: Aetiology and Diagnostic Criteria.

Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent trabeculae protruding into the left ventricular lumen and deep intertrabecular recesses. LVNC can manifest in isolation or alongside other heart muscle diseases. Its occurrence among children is rising due to advancements in imaging techniques. The origins of LVNC are diverse, involving both genetic and acquired forms. The clinical manifestation varies greatly, with some cases presenting no symptoms, while others typically manifesting with heart failure, systemic embolism, and arrhythmias. Diagnosis mainly relies on assessing heart structure using imaging tools like echocardiography and cardiac magnetic resonance. However, the absence of a universally agreed-upon standard and limitations in diagnostic criteria have led to ongoing debates in the scientific community regarding the most reliable methods. Further research is crucial to enhance the diagnosis of LVNC, particularly in early life stages.

[Clinical and genetic manifestations of left ventricular non-compaction in children]. / Caratteristiche cliniche e genetiche del ventricolo sinistro non compatto in età pediatrica.

Left ventricular non-compaction (LVNC) is a myocardial disease characterized by a two-layered structure typically seen at the apical and lateral left portions of the ventricular myocardium, distal to the papillary muscles. While considered a rare disease, its prevalence in children is increasing due to the increased awareness of this condition and improved resolution of imaging techniques. The etiology is heterogeneous, ranging from inherited conditions to acquired diseases. Although many patients are asymptomatic, some patients may experience adverse events, including heart failure, arrhythmias, or thromboembolic events. Several echocardiographic or cardiac magnetic resonance imaging diagnostic criteria have been proposed for diagnosing LVNC. However, their application in children is significantly limited. This review aims to describe the clinical and genetic characteristics of children with LVNC and discuss the role of the proposed diagnostic criteria.

The immune cell landscape of glioblastoma patients highlights a myeloid-enriched and immune suppressed microenvironment compared to metastatic brain tumors.

Introduction: Brain metastases (BrM), which commonly arise in patients with melanoma, breast cancer and lung cancer, are associated with a poor clinical prognosis. In this context, the tumor microenvironment (TME) plays an important role since it either promotes or inhibits tumor progression. Our previous studies have characterized the immunosuppressive microenvironment of glioblastoma (GBM). The aim of this study is to compare the immune profiles of BrM and GBM in order to identify potential differences that may be exploited in their differential treatment. Methods: Tumor and/or blood samples were taken from 20 BrM patients and 19 GBM patients. Multi-parametric flow cytometry was used to evaluate myeloid and lymphoid cells, as well as the expression of immune checkpoints in the TME and blood. In selected cases, the immunosuppressive ability of sorted myeloid cells was tested, and the ex vivo proliferation of myeloid, lymphoid and tumor cell populations was analyzed. Results: High frequencies of myeloid cells dominated both the BrM and GBM landscapes, but a higher presence of tumor-associated macrophages was observed in GBM, while BrM were characterized by a significant presence of tumor-infiltrating lymphocytes. Exhaustion markers were highly expressed in all T cells from both primary and metastatic brain tumors. Ex vivo analysis of the cell cycle of a single sample of a BrM and of a GBM revealed subsets of proliferating tumor cells and blood-derived macrophages, but quiescent resident microglial cells and few proliferating lymphocytes. Macrophages sorted from a single lung BrM exhibited a strong immunosuppressive activity, as previously shown for primary GBM. Finally, a significant expansion of some myeloid cell subsets was observed in the blood of both GBM and BrM patients. Discussion: Our results define the main characteristics of the immune profile of BrM and GBM, which are distinguished by different levels of immunosuppressive myeloid cells and lymphocytes devoid of effector function. Understanding the role of the different cells in establishing the metastatic setting is critical for improving the therapeutic efficacy of new targeted immunotherapy strategies.

Assessing the feasibility of using the antecubital vein to perform right heart catheterization in children and adults with congenital heart disease: a retrospective, observational single-center study.

BACKGROUND: Right heart catheterization (RHC) usually is performed via the femoral vein or the internal jugular vein. However, the antecubital fossa vein is a valid venous access, and it has become increasingly popular to perform right heart catheterization utilizing this access. METHODS: A retrospective, observational study was conducted to describe use of the antecubital fossa vein for right heart catheterization in adults and children with congenital heart disease (CHD). Patients who had undergone RHC via antecubital fossa vein at the authors' hospital between September 2019 and December 2022 were included. The outcomes studied were procedural failure and procedure-related adverse events. RESULTS: Fifty-two patients with CHD underwent right cardiac catheterization via an upper arm vein. The upper arm vein was unable to perform the RHC in only 2 patients (3.8%). Only 1 patient developed a minor adverse event. No irreversible and/or life-threating adverse events were detected. CONCLUSIONS: The upper arm veins are safe and effective to perform a RHC in children and adults with CHD. This approach demonstrates a high percentage of technical success, and few mild complications.

Contact force sensing radiofrequency catheter ablation guided by electroanatomic mapping in pediatric patients with permanent junctional reciprocating tachycardia: A case series.

Limited data are available on the use of irrigated contact force (CF) catheters for radiofrequency (RF) ablation of permanent junctional reciprocating tachycardia (PJRT) in children. We considered five consecutive pediatric patients with diagnosis of PJRT who underwent RF ablation with irrigated CF catheter guided by electroanatomic mapping, obtaining a low number of RF pulses and minimal fluoroscopy exposure. High CF values are not necessary to obtain effective RF lesions and successful ablation.

Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes.

Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9); two patients with MYH7-related myopathy (Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7); one patient with desminopathy (Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES); two patients with mitochondrial myopathy (Patient 6 carried the m.3243A>G variant in MT-TL1; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.

Natural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines.

BACKGROUND: We aimed to examine clinical features and outcomes of consecutive molecularly characterized patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy. METHODS: A retrospective, longitudinal multicenter cohort of consecutive children and adults with a genetic diagnosis of Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy between 2002 and 2019 was assembled. We defined a priori 3 different patterns of left ventricular remodeling during follow-up: (1) an increase in ≥15% of the maximal left ventricular wall thickness (MLVWT), both in mm and z-score (progression); (2) a reduction ≥15% of the MLVWT, both in mm and z-score (absolute regression); (3) a reduction ≥15% of the MLVWT z-score with a stable MLVWT in mm (relative regression). The primary study end point was a composite of cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator-shock. RESULTS: The cohort comprised 42 patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy, with a median age at diagnosis of 3.5 (interquartile range, 0.2-12.3) years. Freedom from primary end point was 92.7% (95% CI, 84.7%-100%) 1 year after presentation and 80.9% (95% CI, 70.1%-90.7%) at 5 years. Patients with MLVWT z-score >13.7 showed reduced survival compared with those with <13.7. During a median follow-up of 3.7 years (interquartile range, 2.6-7.9), absolute regression was the most common type of left ventricular remodeling (n=9, 31%), followed by progression (n=6, 21%), and relative regression (n=6, 21%). CONCLUSIONS: These findings provide insights into the natural history of left ventricular hypertrophy, and can help inform clinicians regarding risk stratification and clinical outcomes in patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.

Myocardial work in children with Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White Syndrome (WPW) has been associated with reduced local myocardial deformation, and when left ventricular dysfunction is present, catheter ablation of the accessory pathway may be required, even in asymptomatic patients. We aimed to evaluate the diagnostic value of non-invasive myocardial work in predicting subtle abnormalities in myocardial performance in children with WPW.Seventy-five paediatric patients (age 8.7 ± 3.5 years) were retrospectively recruited for the study: 25 cases with manifest WPW and 50 age- and sex- matched controls (CTR). Global myocardial work index (MWI) was measured as the area of the left ventricle (LV) pressure-strain loops. From MWI, global Myocardial Constructive Work (MCW), Wasted Work (MWW), and Work Efficiency (MWE) were estimated. In addition, standard echocardiographic parameters of LV function were evaluated. Despite normal LV ejection fraction (EF) and global longitudinal strain (GLS), children with WPW had worse MWI, MCW, MWW, and MWE. At multivariate analysis, MWI and MCW were associated with GLS and systolic blood pressure, and QRS was the best independent predictor of low MWE and MWW. In particular, a QRS > 110 ms showed good sensitivity and specificity for worse MWE and MWW values. In children with WPW, myocardial work indices were found significantly reduced, even in the presence of normal LV EF and GLS. This study supports the systematic use of myocardial work during the follow-up of paediatric patients with WPW. Myocardial work analysis may represent a sensitive measure of LV performance and aid in decision-making.

The role of the pregnancy heart team in clinical practice.

Significant maternal and fetal morbidity and mortality risk has been shown to be associated with cardiovascular disease in pregnancy. Several determinants, such as the increasing number of females with corrected congenital heart disease in reproductive age, a more advanced maternal age associated with cardiovascular risk factors, and a greater prevalence of preexisting comorbidities related to cardiac disorders such as cancer and COVID-19), lead to a higher incidence of cardiac complications in pregnancy in the last few decades. However, adopting a multidisciplinary strategy may influence maternal and neonatal outcomes. This review aims at assessing the role of the Pregnancy Heart Team, which should ensure careful pre-pregnancy counseling, pregnancy monitoring, and delivery planning for both congenital and other cardiac or metabolic disorders, addressing several emerging aspects in the multidisciplinary team-based approach.

[Heart involvement in multisystem inflammatory syndrome in children correlated with SARS-CoV-2 infection: a review by ANMCO/SICP]. / Le manifestazioni cardiache nella sindrome multisistemica infiammatoria del bambino correlate all'infezione da SARS-CoV-2: una rassegna a cura di ANMCO/SICP.

Acute clinical manifestations of COVID-19 are generally less severe in childhood, however a proportion of them can develop a severe systemic hyperinflammatory syndrome after SARS-CoV-2 infection, known as the multisystem inflammatory syndrome (multisystem inflammatory syndrome in children, MIS-C). Cardiovascular manifestations in MIS-C are frequent (34-82%), including myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. The most affected cases can develop cardiogenic shock needing intensive care unit admission, inotropic support and sometimes even mechanical circulatory support. The elevation of myocardial necrosis markers, the frequently transient left ventricular systolic dysfunction and the presence of changes on magnetic resonance imaging, support the hypothesis of an immune-mediated post-viral pathogenesis similar to myocarditis. Although MIS-C shows excellent short-term survival, further studies are needed to demonstrate complete reversibility of residual subclinical heart damage.

Triple Antiarrhythmic Therapy in Newborns with Refractory Atrioventricular Reentrant Tachycardia.

Atrioventricular reentrant tachycardia (AVRT) is the most common form of supraventricular tachycardia in newborns. AVRT is sometimes refractory to conventional antiarrhythmic therapy. We describe our experience about the use of the triple combination of flecainide + propranolol + amiodarone as third-line regimen for refractory and recurrent AVRT in newborns. We considered a series of 14 patients who had failed both first-line and second-line therapy and were treated using the combination of flecainide + propranolol + amiodarone. Transoesophageal electrophysiologic study (TES) was performed to test the effectiveness of medical therapy during hospitalization and to try to reduce the amount of therapy, after amiodarone wash-out, before 1 year of age. TES was repeated at 1 year of age to test the spontaneous resolution of the arrhythmia after treatment discontinuation. Rhythm control was achieved in all 14 patients. At a mean age of 9.3 ± 2 months, AVRT was not inducible by TES in 11/12 amiodarone-free patients. At a mean age of 14.1 ± 3 months, AVRT was still inducible in 7/12 patients after interrupting the entire antiarrhythmic therapy (58.3%). Triple combination was effective as third-line option to suppress AVRT refractory to single and double antiarrhythmic therapy, with no significant adverse events. Our experience suggests that triple therapy could be maintained for a short-term treatment, discontinuing amiodarone before 1 year of age to avoid long-term side effects. Newborns who needed triple therapy appear to have a lower chance of accessory pathway disappearance at 1 year of age. TES could be useful for risk stratification of recurrences at the time of drug discontinuation in infants considered to be at higher risk of recurrent AVRT.

Idiopathic Pulmonary Arterial Hypertension in Paediatrics Represents Still a Serious Challenge: A Case Series Study.

INTRODUCTION: Paediatric pulmonary hypertension (PH) represents a heterogeneous illness that is responsible for high morbidity and mortality if left without treatment. Idiopathic pulmonary arterial hypertension (IPAH) is a subtype of PAH rarely seen in paediatrics. Limited long-term data are available. METHODS: Over a period of 20 years, 10 paediatric patients were enrolled at two tertiary centres. Their clinical, echocardiographic, and right heart catheterisation (RHC) features and outcome were evaluated. RESULTS: The mean age at first diagnosis was 5.7 ± 5.7 years. The age at the last follow-up was 12.4 ± 6.1 years. The average follow-up was 6.6 ± 0.8 years. There was a female prevalence of 60% (p < 0.05) in this case series. Regarding the NYHA functional class, 80% of IPAH subjects were in class III or IV. The mean saturation was 91 ± 5%. In this regard, 70% of the patients were on a combination of three drugs, with sildenafil (90%) included. On echocardiography, longitudinal right ventricular contractility (TAPSE) was slightly reduced (13.4 ± 2.6 mm), whilst RVSP was severely elevated (101 ± 19 mmHg). The RHC data showed that mPAP was 61.8 ± 23.1 mmHg (p = 0.0017 with RVSP on echocardiography), mRAP was 10.7 ± 3.8 mmHg, CI was 2.6 ± 1 L·min-1·m-2, PVRi was 16.8 ± 12.6 WU·m2, and SVO2 was 63.6 ± 14.8%. Regarding the outcome, two male IPAH patients (20%) died, and 50% underwent lung transplant or were on transplant assessment or already on the waiting list for lung transplantation. One patient underwent a ductus arteriosus stenting (reverse Potts shunt) and another underwent atrial septostomy and stenting. CONCLUSIONS: Notwithstanding the progress in medical therapy, IPAH continues to represent a serious challenge, particularly in the paediatric population, with the need for lung transplantation and significant mortality.

The Role of Genetic Testing in Patients with Heritable Thoracic Aortic Diseases.

Heritable thoracic aortic disease (HTAD) is a term used to define a large group of disorders characterized by the occurrence of aortic events, mainly represented by aneurysm or dissection. These events generally involve the ascending aorta, although the involvement of other districts of the aorta or peripheral vessels may occur. HTAD can be classified as non-syndromic if the disorder is limited to the aorta, and syndromic when associated with extra-aortic features. About 20-25% of patients with non-syndromic HTAD exhibit a family history of aortic disease. Thus, a careful clinical evaluation of the proband and the first-degree family members is required to differentiate familial and sporadic cases. Genetic testing is essential since it allows confirmation of the etiological diagnosis of HTAD (particularly in patients with a significant family history) and may guide family screening. In addition, genetic diagnosis significantly impacts patients' management since the different conditions significantly differ with respect to natural history and treatment strategies. The prognosis in all HTADs is determined by the progressive dilation of the aorta, potentially leading to acute aortic events, such as dissection or rupture. Moreover, the prognosis varies according to the underlying genetic mutations. This review aims to describe the clinical characteristics and natural history of the most common HTADs, with particular emphasis on the role of genetic testing in risk stratification and management.