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A heart with a borderline ventricle refers to a situation where there is uncertainty about whether the left or right underdeveloped ventricle can effectively support the systemic or pulmonary circulation with appropriate filling pressures and sufficient physiological reserve. Pediatric cardiologists often deal with congenital heart diseases (CHDs) associated with various degrees of hypoplasia of the left or right ventricles. To date, no specific guidelines exist, and surgical management may be extremely variable in different centers and sometimes even in the same center at different times. Thus, the choice between the single-ventricle or biventricular approach is always controversial. The aim of this review is to better define when “small is too small and large is large enough” in order to help clinicians make the decision that could potentially affect the patient’s entire life.

Abstract Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.

Advances in both imaging techniques and genetics have led to the recognition of a wide variety of aortic anomalies that can be grouped under the term ‘hereditary thoracic aortic diseases’. The present review aims to summarize this very heterogeneous population’s clinical, genetic, and imaging characteristics and to discuss the implications of the diagnosis for clinical counselling (on sports activity or pregnancy), medical therapies and surgical management.

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.

Restrictive cardiomyopathy (RCM) is a rare disease of the myocardium caused by mutations in several genes including TNNT2, DES, TNNI3, MYPN and FLNC. Individuals affected by RCM often develop heart failure at a young age, requiring early heart transplantation. A 7-year-old patient was referred for genetic testing following a diagnosis of restrictive cardiomyopathy. Clinical exome sequencing analysis identified a likely pathogenic mutation in the FLNC gene [(NM_001458.5 c.6527_6547dup p.(Arg2176_2182dup)]. Its clinical relevance was augmented by the fact that this variant was absent in the parents and was thus interpreted as de novo. Genetic testing is a powerful tool to clarify the diagnosis, guide intervention strategies and enable cascade testing in patients with pediatric-onset RCM.

Background: Cardiac involvement is reported in a significant proportion of patients with classical organic acidurias (OAs), contributing to disability and premature death. Different cardiac phenotypes have been described, among which dilated cardiomyopathy (DCM) is predominant. Despite recent progress in diagnosis and treatment, the natural history of patients with OAs remains unresolved, specifically with regard to the impact of cardiac complications. We therefore performed a retrospective study to address this issue at our Referral Center for Pediatric Inherited Errors of Metabolism. Methods: Sixty patients with OAs (propionic (PA), methylmalonic (MMA) and isovaleric acidemias and maple syrup urine disease) diagnosed from 2000 to 2022 were systematically assessed at baseline and at follow-up. Results: Cardiac anomalies were found in 23/60 OA patients, all with PA or MMA, represented by DCM (17/23 patients) and/or acquired long QT syndrome (3/23 patients). The presence of DCM was associated with the worst prognosis. The rate of occurrence of major adverse cardiac events (MACEs) at 5 years was 55% in PA with cardiomyopathy; 35% in MMA with cardiomyopathy; and 23% in MMA without cardiomyopathy. Liver transplantation was performed in seven patients (12%), all with PA or MMA, due to worsening cardiac impairment, and led to the stabilization of metabolic status and cardiac function. Conclusions: Cardiac involvement was documented in about one third of children diagnosed with classical OAs, confined to PA and MMA, and was often associated with poor outcome in over 50%. Etiological diagnosis of OAs is essential in guiding management and risk stratification.

Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular pathophysiology determined by increased myocardial stiffness. While suspicion of RCM is initially raised by clinical evaluation and supported by electrocardiographic and echocardiographic findings, invasive hemodynamic evaluation is often required for diagnosis and management of patients during follow-up. RCM is commonly associated with a poor prognosis and a high incidence of heart failure, and PH is reported in paediatric patients with RCM. Currently, only a few therapies are available for specific RCM aetiologies. Early referral to centres for advanced heart failure treatment is often necessary. The aim of this review is to address questions frequently asked when facing paediatric patients with RCM, including issues related to aetiologies, clinical presentation, diagnostic process and prognosis.

The incidence of atrial fibrillation (AF) during pregnancy increases with maternal age and with the presence of structural heart disorders. Early diagnosis and prompt therapy can considerably reduce the risk of thromboembolism. The therapeutic approach to AF during pregnancy is particularly challenging, and the maternal and fetal risks associated with the use of antiarrhythmic and anticoagulant drugs must be carefully evaluated. Moreover, the currently used thromboembolic risk scores have yet to be validated for the prediction of stroke during pregnancy. At present, electrical cardioversion is considered to be the safest and most effective strategy in women with hemodynamic instability. Beta-selective blockers are also recommended as the first choice for rate control. Antiarrhythmic drugs such as flecainide, propafenone and sotalol should be considered for rhythm control if atrioventricular nodal-blocking drugs fail. AF catheter ablation is currently not recommended during pregnancy. Overall, the therapeutic strategy for AF in pregnancy must be carefully assessed and should take into consideration the advantages and drawbacks of each aspect. A multidisciplinary approach with a “Pregnancy-Heart Team” appears to improve the management and outcome of these patients. However, further studies are needed to identify the most appropriate therapeutic strategies for AF in pregnancy.

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population.

Abstract The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options. The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors. Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron). These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children. AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories. Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts’ agreement. This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.

Abstract Aims Children presenting with hypertrophic cardiomyopathy (HCM) in infancy are reported to have a poor prognosis, but this heterogeneous group has not been systematically characterized. This study aimed to describe the aetiology, phenotype, and outcomes of infantile HCM in a well‐characterized multicentre European cohort. Methods and results Of 301 children diagnosed with infantile HCM between 1987 and 2019 presenting to 17 European centres [male n = 187 (62.1%)], underlying aetiology was non‐syndromic (n = 138, 45.6%), RASopathy (n = 101, 33.6%), or inborn error of metabolism (IEM) (n = 49, 16.3%). The most common reasons for presentation were symptoms (n = 77, 29.3%), which were more prevalent in those with syndromic disease (n = 62, 61.4%, P

BackgroundSudden cardiac arrest (SCA) in young people represents a dramatic event, often leading to severe neurologic outcomes or sudden cardiac death (SCD), and is frequently caused by genetic heart diseases. In this study, we report the results of the Tuscany registry of sudden cardiac death (ToRSADE) registry, aimed at monitoring the incidence and investigating the genetic basis of SCA and SCD occurring in subjects < 50 years of age in Tuscany, Italy.Methods and resultsCreation of the ToRSADE registry allowed implementation of a repository for clinical, molecular and genetic data. For 22 patients, in whom a genetic substrate was documented or suspected, blood samples could be analyzed; 14 were collected at autopsy and 8 from resuscitated patients after SCA. Next generation sequencing (NGS) analysis revealed likely pathogenetic (LP) variants associated with cardiomyopathy (CM) or channelopathy in four patients (19%), while 17 (81%) carried variants of uncertain significance in relevant genes (VUS). In only one patient NGS confirmed the diagnosis obtained during autopsy: the p.(Asn480Lysfs*20) PKP2 mutation in a patient with arrhythmogenic cardiomyopathy (AC).ConclusionSystematic genetic screening allowed identification of LP variants in 19% of consecutive patients with SCA/SCD, including subjects carrying variants associated with hypertrophic cardiomyopathy (HCM) or AC who had SCA/SCD in the absence of structural cardiomyopathy phenotype. Genetic analysis combined with clinical information in survived patients and post-mortem evaluation represent an essential multi-disciplinary approach to manage juvenile SCD and SCA, key to providing appropriate medical and genetic assistance to families, and advancing knowledge on the basis of arrhythmogenic mechanisms in inherited cardiomyopathies and channelopathies.

Background: Aortic dilation (AoD) is commonly reported in patients with bicuspid aortic valve (BAV) and has been related to flow abnormalities and genetic predisposition. AoD-related complications are reported to be extremely rare in children. Conversely, an overestimate of AoD related to body size may lead to excess diagnoses and negatively impact quality of life and an active lifestyle. In the present study, we compared the diagnosis performance of the newly introduced Q-score (based on a machine-learning algorithm) versus the traditional Z-score in a large consecutive pediatric cohort with BAV. Materials and methods: Prevalence and progression of AoD were evaluated in 281 pediatric patients ages > 5 and < 18 years at first observation, 249 of whom had isolated BAV and 32 had BAV associated with aortic coarctation (CoA–BAV). An additional group of 24 pediatric patients with isolated CoA was considered. Measurements were made at the level of the aortic annulus, Valsalva sinuses, sinotubular aorta, and proximal ascending aorta. Both Z-scores using traditional nomograms and the new Q-score were calculated at baseline and at followup (mean 4.5 years). Results: A dilation of the proximal ascending aorta was suggested by traditional nomograms (Z-score > 2) in 31.2% of patients with isolated BAV and 18.5% with CoA–BAV at baseline and in 40.7% and 33.3%, respectively, at followup. No significant dilation was found in patients with isolated CoA. Using the new Q-score calculator, ascending aorta dilation was detected in 15.4% of patients with BAV and 18.5% with CoA–BAV at baseline and in 15.8% and 3.7%, respectively, at followup. AoD was significantly related to the presence and degree of aortic stenosis (AS) but not to aortic regurgitation (AR). No AoD-related complications occurred during the followup. Conclusions: Our data confirm the presence of ascending aorta dilation in a consistent subgroup of pediatric patients with isolated BAV, with progression during followup, while AoD was less common when CoA was associated with BAV. A positive correlation was found with the prevalence and degree of AS, but not with AR. Finally, the nomograms used may significantly influence the prevalence of AoD, especially in children, with a possible overestimation by traditional nomograms. This concept requires prospective validation in long-term followup.

Abstract Background Supraventricular tachycardias (SVTs) are common in the first year of life and may be life-threatening. Acute cardioversion is usually effective, with both pharmacological and non-pharmacological procedures. However, as yet no international consensus exists concerning the best drug required for a stable conversion to sinus rhythm (maintenance treatment). Our study intends to describe the experience of a single centre with maintenance drug treatment of both re-entry and automatic SVTs in the first year of life. Methods From March 1995 to April 2019, 55 patients under one year of age with SVT were observed in our Centre. The SVTs were divided into two groups: 45 re-entry and 10 automatic tachycardias. As regards maintenance therapy, in re-entry tachycardias, we chose to start with oral flecainide and in case of relapses switched to combined treatment with beta-blockers or digoxin. In automatic tachycardias we first administered a beta-blocker, later combined with flecainide or amiodarone when ineffective. Results The patients’ median follow-up time was 35 months. In re-entry tachycardias, flecainide was effective as monotherapy in 23/45 patients (51.1%) and in 20/45 patients (44.4%) in combination with nadolol, sotalol or digoxin (overall 95.5%). In automatic tachycardias, a beta-blocker alone was effective in 3/10 patients (30.0%), however, the best results were obtained when combined with flecainide: overall 9/10 (90%). Conclusions In this retrospective study on pharmacological treatment of SVTs under 1 year of age the combination of flecainide and beta-blockers was highly effective in long-term maintenance of sinus rhythm in both re-entry and automatic tachycardias.

Abstract Genetic investigation of early‐onset Dilatative cardiomyopathy phenotype, including molecular autopsy, is the key to appropriate recognition and management of rare etiologies and atypical presentations and to offer genetic counseling to the family.

Abstract Background Primary mitochondrial disorders (PMD) are rare conditions resulting in progressive multi-organ failure. Cardiovascular involvement (CVI) has been reported in paediatric patients. However, its age-related prevalence, clinical presentation and prognostic impact are unresolved. We detailed CVI in a cohort of children diagnosed with PMD over two decades at a tertiary referral centre. Results We enrolled 86 PMD patients (M/F = 30/56; mean age 6.4 ± 8.58 years). CVI was detected in 31 patients (36%), with mean age at onset of 5.7 ± 7.8 years including the pre- and neonatal phase in 14, often representing the first sign of PMD (42% of those with CVI). Heart disease resulted more common in males and in children with specific aetiologies (Barth, TMEM70 and MELAS syndromes). Hypertrophic, non-compaction and dilated cardiomyopathies were the prevalent disorders, although pulmonary arterial hypertension was also found. Adverse cardiac events (heart failure, resuscitated cardiac arrest, ICD/PM implantation, sudden death) occurred in 19% of children with CVI over a follow-up period of 5.4 ± 4.3 years. All-cause mortality was higher in patients with CVI compared to those without CVI (45.1% vs 21.8%; p

Hutchinson–Gilford progeria syndrome is an extremely rare genetic disease caused by a de novo mutation in the LMNA gene, leading to an accumulation of a form of Lamin A, called Progerin, which results in a typical phenotype and a marked decrease in life expectancy, due to early atherosclerosis and cardiovascular disease. We report the case of a fourteen-year-old Chinese boy with Hutchinson–Gilford progeria syndrome admitted to the emergency room because of precordial pain. Physical examination showed tachycardia 130 beats/min and arterial hypertension: 170/120 mmHg, normal respiratory rate, no neurological impairment; ECG evidenced sinus tachycardia, left ventricular hypertrophy, horizontal ST-segment depression in I, aVL, II, III, aVF leads, and V4–V6 and ST-segment elevation in aVR and V1 leads. Echocardiography highlighted preserved global left ventricular function with concentric hypertrophy, altered diastolic flow pattern, mitral valve insufficiency, and minimal aortic regurgitation. Blood tests evidenced an increase in high-sensitivity troponin T level (335 pg/mL). NSTEMI diagnosis was performed, and the patient was admitted to the intensive care unit. A coronary CT angiography showed a severe obstruction of the common trunk of the left coronary artery, for which an urgent percutaneous coronary intervention (PCI) was proposed. A selective coronary angiography imaged complete chronic occlusion of the left main coronary artery as well as severe stenosis at the origin of a very enlarged right coronary artery that vascularized the left coronary artery through collaterals. Afterwards, the right coronary artery was probed using an Amplatz right (AR1) guiding catheter, through which a large 3.5 mm drug-eluting coronary stent (Xience Sierra, Abbott, Abbott Park, IL, USA) was implanted. At the end of the procedure, no residual stenosis was imaged and improved vascularization of the left coronary artery distribution segments was observed. Dual antiplatelet therapy (DAPT) consisting of aspirin (75 mg daily) and clopidogrel (37.5 mg daily) and anti-hypertensive therapy were started. At the one-year follow-up, the patient had not reported any occurrence of anginal chest pain.

A 12-year-old male patient suffering from congenital glaucoma developed bradycardia, left ventricular failure, and hypotension after induction of anesthesia. Electrocardiography and echocardiography revealed a complete normalization of ECG and a complete spontaneous recovery in the cardiac function 72 hours from the beginning of the clinical manifestations, while cardiac Magnetic Resonance Imaging was performed, and coronary Computed Tomography scan revealed a myocardial bridge of a tract of the left anterior descendent coronary artery. Diagnosis of Kounis syndrome (KS) was made, a relatively novel, under-recognized clinical condition, defined as the manifestation of an acute coronary syndrome accompanied by mast cell activation and platelet aggregation involving interrelated and interacting inflammatory cells in the setting of allergic, hypersensitivity, anaphylactic or anaphylactoid insults. We described one of the first pediatric cases of KS related to anesthetic medications. In children, this syndrome has been only described in isolated case reports or small case series. Thus, it appears critical to report new cases of KS in children to increase the awareness of this disease in pediatric healthcare workers so as to enhance its early recognition and optimal therapeutic strategy. Furthermore, it appears of paramount importance the implementation of universal guidelines accepted by allergology and cardiology societies, in order to standardize the management of pediatric and adult patients with KS. Finally, a close collaboration between pediatric allergists and cardiologists seems fundamental for an optimal multidisciplinary patient care.

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Prevalence of isolated BAV in the general pediatric population is about 0.8%, but it has been reported to be as high as 85% in patients with aortic coarctation. A genetic basis has been recognized, with great heterogeneity. Standard BAV terminology, recently proposed on the basis of morpho-functional assessment by transthoracic echocardiography, may be applied also to the pediatric population. Apart from neonatal stenotic BAV, progression of valve dysfunction and/or of the associated aortic dilation seems to be slow during pediatric age and complications are reported to be much rarer in comparison with adults. When required, because of severe BAV dysfunction, surgery is most often the therapeutic choice; however, the ideal initial approach to treat severe aortic stenosis in children or adolescents is not completely defined yet, and a percutaneous approach may be considered in selected cases as a palliative option in order to postpone surgery. A comprehensive and tailored evaluation is needed to define the right intervals for cardiologic evaluation, indications for sport activity and the right timing for intervention.

Mucopolysaccharidosis are genetic disorders due to deficiency of lysosomal enzymes, resulting in abnormal glycosaminoglycans accumulation in several tissues. Heart involvement tends to be progressive and worsens with age. We describe the first case of mucopolysaccharidosis type I presenting with noncompaction/dilated-mixed cardiomyopathy and heart failure within neonatal period, which responded successfully to specific metabolic treatment. Cardiac function recovered after enzyme replacement therapy and hematopoietic stem cell transplantation, adding to the existing knowledge of the disease.

Familial dilated cardiomyopathy (DCM) is mostly caused by mutations in genes encoding cytoskeletal and sarcomeric proteins. In the pediatric population, DCM is the predominant type of primitive myocardial disease. A severe form of DCM is associated with mutations in the DMD gene encoding dystrophin, which are the cause of Duchenne Muscular Dystrophy (DMD). DMD-associated cardiomyopathy is still poorly understood and orphan of a specific therapy. In the last 5 years, a rise of interest in disease models using human induced pluripotent stem cells (hiPSCs) has led to more than 50 original studies on DCM models. In this review paper, we provide a comprehensive overview on the advances in DMD cardiomyopathy disease modeling and highlight the most remarkable findings obtained from cardiomyocytes differentiated from hiPSCs of DMD patients. We will also describe how hiPSCs based studies have contributed to the identification of specific myocardial disease mechanisms that may be relevant in the pathogenesis of DCM, representing novel potential therapeutic targets.

Background: To develop a tool for assessing normalcy of the thoracic aorta (TA) by echocardiography, based on either a linear regression model (Z-score), or a machine learning technique, namely one-class support vector machine (OC-SVM) (Q-score). Methods: TA diameters were measured in 1112 prospectively enrolled healthy subjects, aging 5 to 89 years. Considering sex, age and body surface area we developed two calculators based on the traditional Z-score and the novel Q-score. The calculators were compared in 198 adults with TA > 40 mm, and in 466 patients affected by either Marfan syndrome or bicuspid aortic valve (BAV). Results: Q-score attained a better Area Under the Curve (0.989; 95% CI 0.984–0.993, sensitivity = 97.5%, specificity = 95.4%) than Z-score (0.955; 95% CI 0.942–0.967, sensitivity = 81.3%, specificity = 93.3%; p < 0.0001) in patients with TA > 40 mm. The prevalence of TA dilatation in Marfan and BAV patients was higher as Z-score > 2 than as Q-score < 4% (73.4% vs. 50.09%, p < 0.00001). Conclusions: Q-score is a novel tool for assessing TA normalcy based on a model requiring less assumptions about the distribution of the relevant variables. Notably, diameters do not need to depend linearly on anthropometric measurements. Additionally, Q-score can capture the joint distribution of these variables with all four diameters simultaneously, thus accounting for the overall aortic shape. This approach results in a lower rate of predicted TA abnormalcy in patients at risk of TA aneurysm. Further prognostic studies will be necessary for assessing the relative effectiveness of Q-score versus Z-score.

Aim. We investigated the predictors of tissue Doppler left ventricular (LV) longitudinal indexes in a healthy Italian pediatric population and established normative data and regression equations for the calculation of z scores. Methods and Results. A total of 369 healthy subjects aged 1–17 years (age of 6.4 ± 1.1 years, 49.1% female) underwent echocardiography. LV peak longitudinal velocity at systole (s'), early diastole (e'), and late diastole (a') was determined by tissue Doppler. The ratio of peak early diastolic LV filling velocity to e' was calculated. Age was the only independent determinant of s' (β=0.491, p