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DCM is the leading cause of death in Duchenne patients. LVADs are considered as therapeutic options as DT in advanced HF. The aim of our study was to evaluate LV remodeling of Duchenne after LVADs and chronic therapy. Demographic and echocardiographic data of 8 Duchenne patients implanted with LVADs were reviewed and analyzed. All measures were collected before LVAD implantation, after 1 month and 1 year. All patients were affected by end-stage DCM, and mean age at implantation was 16.9 ± 2.9 years. Patients were treated with maximal medical therapy. One-year post-implantation HR decreased from a mean of 110 ± 19 bpm to 82 ± 2 bpm (P = .002), and a significant decrease in LV volumes and diameters LVEDD P = .03, LVESD P = .02, EDV P = .01, and ESV P = .02) was noticed together with a significant increase in EF (P = .0036). However, RWT did not change over time, showing an eccentric remodeling pattern pre- and post-LVADs. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function secondary to a significant ventricular unloading due to LVADs coupled with chronic therapy.

Duchenne muscular dystrophy (DMD) cardiomyopathy (DCM) is characterized by a hypokinetic, dilated phenotype progressively increasing with age. Regular cardiac care is crucial in DMD care. Early recognition and prophylactic use of angiotensin converting enzyme inhibitors (ACEi) are the main stay therapeutic strategy to delay incidence of DMD-DCM. Pharmacological treatment to improve symptoms and left ventricle (LV) systolic function, have been widely implemented in the past years. Because of lack of DMD specific drugs, actual indications for established DCM include current treatment for heart failure (HF). This review focuses on current HF strategies to identify, characterize, and treat DMD-DCM.

Background Nonfluoroscopic 3-dimensional (3D) electroanatomic mapping systems (EAMs) have been developed to guide cardiac catheter navigation and reduce fluoroscopy. Selective right ventricular (RV) septal pacing could prevent pacing-induced left ventricular (LV) dysfunction. Objective The purpose of this study was to determine whether EAM-guided selective RV septal pacing preserves LV contractility/synchrony in pediatric patients with complete atrioventricular block (CAVB) and no other congenital heart defects. Methods Prospective analysis of children/adolescents who underwent EAM-guided selective RV pacing was performed. A 3D pacing map guided ventricular lead implantation at septal sites with narrow paced QRS. Serial echocardiograms were obtained after pacemaker implantation to monitor for function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index). Data are reported as median (25th–75th percentile). Results Thirty-two CAVB patients (age 9.8 [7.0–14.0] years; 11 with a previous pacing system) underwent selective RV septal pacing (13 DDD, 19 VVIR pacemaker; midseptum 22, parahisian 7, RV outflow tract 3) with narrow paced QRS (110 [100–120] ms) and low radiation exposure. Follow-up over 24 (5–33) months showed preserved LV function and synchrony, without significant differences between pacing sites (midseptum–parahisian) and mode (VVIR-DDD). EF decreased after implantation in patients without previous pacing, although values were mainly within normal limits. Three parahisian patients underwent early lead repositioning. Conclusion EAM-guided selective RV septal pacing is a feasible technique associated with preserved LV systolic function and synchrony and low radiation exposure in pediatric patients with CAVB.

Background CACNA1C is a gene encoding the CaV1.2 calcium channel and several cardiac conditions are potentially associated with pathogenic variants in this gene. The aim of this study is to explore genotype-phenotype correlations related to CACNA1C ever described variants and vast phenotypic spectrum.MethodsWe analyzed 102 patients with CACNA1C variants (CACNA1Cv) (9 our cohort and 93 from literature). We studied the association between CACNA1Cv and clinical parameters: arrhythmias, structural heart defects, cardiomyopathy and survival. We followed the American College Medical Genetics (ACMG) scoring system to grade variants’ pathogenicity and their domains.Results CACNA1Cvwith high ACMG scores were associated with higher mortality than variants with lower scores (p CACNA1Cv in Cytoplasmic and Transmembrane domains were associated with higher mortality than other domains (p = 0.005). Multivariate analysis for higher ACMG scores, indicates cardiomyopathy and a lesser extent domain, as independent risk factor for mortality (p = 0.031 and p = 0.04). Cytoplasmic domain variants were frequently associated with long-QT syndrome; C-terminal variants were often linked to Brugada syndrome. Parental mosaicism was relatively high (4–5%) and must not be overlooked in parents’ phenotypic analysis and in calculation of disease recurrence riskConclusionTo the best of our knowledge, this is the first study trying to create genotype-phenotype correlation and better risk stratification in CACNA1Cv in relation to survival and long-term results.

Background Psychological distress is a major issue among survivors of women’s cancer who face numerous barriers to accessing in-person mental health treatments. Mobile phone app–based interventions are scalable and have the potential to increase access to mental health care among survivors of women’s cancer worldwide. Objective This study aimed to evaluate the acceptability and preliminary efficacy of a novel app-based intervention with phone coaching in a sample of survivors of women’s cancer. Methods In a single-group, pre-post, 6-week pilot study in the United States, 28 survivors of women’s cancer used iCanThrive, a novel app intervention that teaches skills for coping with stress and enhancing well-being, with added phone coaching. The primary outcome was self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale). Emotional self-efficacy and sleep disruption were also assessed at baseline, 6-week postintervention, and 4 weeks after the intervention period. Feedback obtained at the end of the study focused on user experience of the intervention. Results There were significant decreases in symptoms of depression and sleep disruption from baseline to postintervention. Sleep disruption remained significantly lower at 4-week postintervention compared with baseline. The iCanThrive app was launched a median of 20.5 times over the intervention period. The median length of use was 2.1 min. Of the individuals who initiated the intervention, 87% (20/23) completed the 6-week intervention. Conclusions This pilot study provides support for the acceptability and preliminary efficacy of the iCanThrive intervention. Future work should validate the intervention in a larger randomized controlled study. It is important to develop scalable interventions that meet the psychosocial needs of different cancer populations. The modular structure of the iCanThrive app and phone coaching could impact a large population of survivors of women’s cancer.

BACKGROUND Small retrospective studies reported that left ventricular (LV) pacing is likely to preserve LV function in children with isolated congenital complete atrioventricular block (CCAVB). The aim of this study was to prospectively evaluate LV contractility and synchrony in a cohort of neonates/infants at pacemaker implantation and follow-up. METHODS Patients with CCAVB who underwent LV pacing were evaluated with electrocardiogram and echocardiogram in a single-center, prospective study. Data were collected at implantation, at 1-month and every year of follow-up, up to 5 years. LV ventricular dimensions (diameters and volumes), systolic function (ejection fraction [EF] and global longitudinal strain [GLS]), and synchrony were evaluated. Data are reported as median (25th-75th centiles). RESULTS Twenty consecutive patients with CCAVB underwent pacemaker implantation (12 single-chamber pacemaker [VVIR] and eight dual-chamber pacemaker [DDD]) with epicardial leads: 17 on the LV apex and three on the free wall. Age at implantation was 0.3 months (1 day-4.5 months). Patients showed good clinical status, normal LV dimensions, preserved systolic function, and synchrony at 60 (30-60) months follow-up. EF increased to normal values in patients with preimplantation EF

Background RASopathies are a set of relatively common autosomal dominant clinically and genetically heterogeneous disorders. Cardiac outcomes in terms of mortality and morbidity for common heart defects (such as pulmonary valve stenosis and hypertrophic cardiomyopathy) have been reported. Nevertheless, also Atypical Cardiac Defects (ACDs) are described. The aim of the present study was to report both prevalence and cardiac outcome of ACDs in patients with RASopathies. Methods A retrospective, multicentric observational study (CArdiac Rasopathy NETwork-CARNET study) was carried out. Clinical, surgical, and genetic data of the patients who were followed until December 2019 were collected. Results Forty-five patients out of 440 followed in CARNET centers had ACDs. Noonan Syndrome (NS), NS Multiple Lentigines (NSML) and CardioFacioCutaneous Syndrome (CFCS) were present in 36, 5 and 4 patients, respectively. Median age at last follow-up was 20.1 years (range 6.9-47 years). Different ACDs were reported, including mitral and aortic valve dysfunction, ascending and descending aortic arch anomalies, coronary arteries dilation, enlargement of left atrial appendage and isolated pulmonary branches diseases. Five patients (11%) underwent cardiac surgery and one of them underwent a second intervention for mitral valve replacement and severe pericardial effusion. No patients died in our cohort until December 2019. Conclusions Patients with RASopathies present a distinct CHD spectrum. Present data suggest that also ACDs must be carefully investigated for their possible impact on the clinical outcome. A careful longitudinal follow up until the individuals reach an adult age is recommended.

International audience; Aims: Cardiomyopathies are a heterogeneous group of disorders that increase the risk for atrial fibrillation (AF). The aim of the study is to assess the prevalence of AF, anticoagulation management, and risk of stroke/transient ischaemic attack (TIA) in patients with cardiomyopathy.Methods and results: Three thousand two hundred eight consecutive adult patients with cardiomyopathy (34.9% female; median age: 55.0 years) were prospectively enrolled as part of the EURObservational Research Programme Cardiomyopathy/Myocarditis Registry. At baseline, 903 (28.2%) patients had AF (29.4% dilated, 27.5% hypertrophic, 51.5% restrictive, and 14.7% arrhythmogenic right ventricular cardiomyopathy, P < 0.001). AF was associated with more advanced New York Heart Association class (P < 0.001), increased prevalence of cardiovascular risk factors and co-morbidities, and a history of stroke/TIA (P < 0.001). Oral anticoagulation was administered in 71.7% of patients with AF (vitamin K antagonist: 51.6%; direct oral anticoagulant: 20.1%). At 1 year follow-up, the incidence of cardiovascular endpoints was as follows: stroke/TIA 1.85% (AF vs. non-AF: 3.17% vs. 1.19%, P < 0.001), death from any cause 3.43% (AF vs. non-AF: 5.39% vs. 2.50%, P < 0.001), and death from heart failure 1.67% (AF vs. non-AF: 2.44% vs. 1.31%, P = 0.033). The independent predictors for stroke/TIA were as follows: AF [odds ratio (OR) 2.812, P = 0.005], history of stroke (OR 7.311, P = 0.010), and anaemia (OR 3.119, P = 0.006).Conclusions: The study reveals a high prevalence and diverse distribution of AF in patients with cardiomyopathies, inadequate anticoagulation regimen, and high risk of stroke/TIA in this population.

Infantile onset cardiomyopathies are highly heterogeneous with several phenocopies compared with adult cardiomyopathies. Multidisciplinary management is essential in determining the underlying etiology in children's cardiomyopathy. Elevated urinary excretion of 3-methylglutaconic acid (3-MGA) is a useful tool in identifying the etiology in some metabolic cardiomyopathy. Here, we report the delayed appearance of 3-MGA-uria, between 6 and 18 months in three patients (out of 100 childhood onset cardiomyopathy) with neonatal onset cardiomyopathy, secondary to TMEM70 mutations and TAZ mutations (Barth syndrome), in whom extensive metabolic investigations, performed in the first weeks of life, did not display 3-MGA-uria. Serial retrospective evaluations showed full characteristic features of TMEM70 and TAZ mutations (Barth syndrome) in these three patients, including a clearly abnormal monolysocardiolipin/cardiolipin ratio in the two Barth syndrome patients. Serially repeated metabolic investigations finally discovered the 3-MGA-uria biomarker in all three patients between the age of 6 and 18 months. Our observation provides novel insights into the temporal appearance of 3-MGA-uria in TMEM70 and TAZ mutations (Barth syndrome) and focus the importance of multidisciplinary management and careful evaluation of family history and red flag signs for phenocopies in infantile onset cardiomyopathies.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. Results: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P P =0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3–10.8], P =0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). Conclusions: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.

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

Background: The impact of genetic syndromes on cardiac magnetic resonance imaging (cMRI) parameters, particularly on right and/or left ventricular dysfunction, associated with clinical parameters following the repair of Tetralogy of Fallot (rToF) is not well known. Therefore, this study aimed to assess the differences in clinical, surgical, and cMRI data in syndromic and non-syndromic rToF patients. Methods: All syndromic rToF patients undergoing a cMRI without general anesthesia between 2010 and 2020 who were able to match with non-syndromic ones for birth date, sex, type of surgery, timing of cMRI, and BSA were selected. Demographic, clinical, surgical, MRI, ECG, and Holter ECG data were collected. Results: A total of one hundred and eight rToF patients equally subdivided into syndromic and non-syndromic, aged 18.7 ± 7.3 years, were studied. Del22q11.2 and Down syndrome (DS) were the most frequent syndromes (42.6% and 31.5%, respectively). Regarding the cMRI parameters considered, left ventricular (LV) dysfunction (LVEF < 50%) was more frequently found in syndromic patients (p = 0.040). In addition, they were older at repair (p = 0.002) but underwent earlier pulmonary valve replacement (PVR) (15.9 ± 5.6 vs. 19.5 ± 6.0 years, p = 0.049). On multivariate Cox regression analysis, adjusted for age at first repair, LV dysfunction remained significantly more associated with DS than del22q11.2 and non-syndromic patients (HR of 5.245; 95% CI 1.709–16.100, p = 0.004). There were only four episodes of non-sustained ventricular tachycardia in our cohort. Conclusions: Among the cMRI parameters commonly taken into consideration in rToF patients, LV dysfunction seemed to be the only one affected by the presence of a genetic syndrome. The percentage of patients performing PVR appears to be similar in both populations, although syndromic patients were older at repair and younger at PVR. Finally, the number of arrhythmic events in rToF patients seems to be low and unaffected by chromosomal abnormalities.

Guidelines for the implantation of cardiac implantable electronic devices (CIEDs) have evolved since publication of the initial ACC/AHA pacemaker guidelines in 1984 [ 1 ]. CIEDs have evolved to include novel forms of cardiac pacing, the development of implantable cardioverter defibrillators (ICDs) and the introduction of devices for long term monitoring of heart rhythm and other physiologic parameters. In view of the increasing complexity of both devices and patients, practice guidelines, by necessity, have become increasingly specific. In 2018, the ACC/AHA/HRS published Guidelines on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay [ 2 ], which were specific recommendations for patients >18 years of age. This age-specific threshold was established in view of the differing indications for CIEDs in young patients as well as size-specific technology factors. Therefore, the following document was developed to update and further delineate indications for the use and management of CIEDs in pediatric patients, defined as ≤21 years of age, with recognition that there is often overlap in the care of patents between 18 and 21 years of age. This document is an abbreviated expert consensus statement (ECS) intended to focus primarily on the indications for CIEDs in the setting of specific disease/diagnostic categories. This document will also provide guidance regarding the management of lead systems and follow-up evaluation for pediatric patients with CIEDs. The recommendations are presented in an abbreviated modular format, with each section including the complete table of recommendations along with a brief synopsis of supportive text and select references to provide some context for the recommendations. This document is not intended to provide an exhaustive discussion of the basis for each of the recommendations, which are further addressed in the comprehensive PACES-CIED document [ 3 ], with further data easily accessible in electronic searches or textbooks.

Background Heterotaxy syndrome (HS) is a group of congenital disorders characterized by abnormal arrangement of thoraco-abdominal organs across the left-right axis of the body, classified as right (RAI) and left atrial isomerism (LAI)·We investigated the long-term survival and phenotypic spectrum in our HS cohort. Results are compared to literature data. Methods This is a single centre, observational, both retro and prospective study. Cardiac features, surgical management and abdominal ultrasound (US) of all HS patients were reviewed or investigated if missing. We evaluated all anatomical data and their clinical impact on survival, arrhythmias, infections, and heart transplant (HT). Results 136 patients were classified as RAI (81) and LAI (55). Long-term survival and freedom from HT reached 69.8% and 87.8% at 40 years in RAI and LAI, respectively. Multivariate analysis showed that LAI is an independent predictor for pacemaker implantation (p = 0.019). Splenic status varied in both groups: in RAI, abdominal US showed asplenia, polysplenia and normal spleen in 48%, 4% and 32% of patients, respectively, whereas in LAI polysplenia, asplenia and normal spleen occurred in 64%, 4% and 16% of cases, respectively. Conclusions Mortality was significantly lower (9%) compared to literature (50%). Although patients with RAI experienced a higher mortality, no independent predictors were found. We demonstrated that the obsolete cardiac definition of "asplenia" and "polysplenia" instead of RAI and LAI is misleading, because of the high variability of the splenic phenotype among patients of both groups.

Background Alternative right ventricular (RV) sites (RVAPS) have been proposed to prevent or reduce RV pacing-induced left-ventricular (LV) dysfunction. Nonfluoroscopic 3D electroanatomic mapping systems (EAM) have been developed to guide cardiac catheter navigation and reduce fluoroscopy during electrophysiological procedures or pacemaker implantations. Aim The aim of the study was to compare the results of EAM-guided permanent pacemaker implantation aiming at RVAPS with conventional fluoroscopic-guided implantation in RV apex (RVA) in children and adolescents. Methods A prospective, randomized analysis was performed on children/adolescents with complete atrioventricular block (CAVB) who underwent EAM-guided pacemaker and transvenous leads implantation into RVAPS (EAM-RVAPS) or conventional, fluoroscopic-guided implantation into RV apex (RVA). In EAM-RVAPS, a pacing map guided the implantation of ventricular leads in septal sites with narrower QRS. After implantation, LV contractility (ejection fraction [EF], Global Longitudinal Strain [GLS]) and synchrony were evaluated at 1-12 months. Results Twenty-one pediatric patients with CAVB, with (six patients) or without structural heart diseases, aged 4-16 (median 10.5) years, were divided in two groups: EAM-RVAPS (11 patients, four dual-chamber/DDD, seven single-chamber/VVIR pacemakers) and RVA (10 patients, one DDD/nine VVIR). The two groups did not show significant differences for preoperative parameters. EAM-RVAPS showed: preserved LVEF and synchrony (not significantly different than RVA), significantly lower GLS and radiation doses/exposures, in spite more complex procedures, significantly longer procedure times and narrower paced QRS than RVA. Conclusions EAM-guided procedures have been useful to reduce radiation exposure and to localize RVAPS with narrower paced QRS and lower GLS than RVA.

Aims Use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) to prevent sudden cardiac death is increasing. Few data exist on S-ICD in young patients. We reviewed our single-centre experience in order to assess the effectiveness and safety of S-ICD implantation, and to identify potential factors associated with complications. Methods and results Observational, non-randomized, standard-of-care study on S-ICD implantation/follow-up in young patients with inherited arrhythmias (IA), cardiomyopathies, and congenital heart defects (CHD). Fifteen patients (6 CHD, 8 cardiomyopathies, and 1 IA), median age 15 years (25th-75th centiles, 14-28), 10 of them

Arrhythmias have acquired a specific identity in pediatric cardiology, but for pediatric cardiologists it has always been difficult to recognize and treat them. Changes in anatomy and physiology result in electrocardiogram features that differ from the normal adult pattern and vary according to the age of the child. Sinus arrhythmia, ectopic atrial rhythm, "wandering pacemaker," and junctional rhythm can be normal characteristics in children (15%-25% of healthy children can have these rhythms on the electrocardiogram). Tachyarrhythmias and bradyarrhythmias must be treated according to the severity of symptoms, and the patient's age and weight.

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy.

Right ventricular failure (RVF) is a significant issue when considering left ventricular assist device (LVAD) implantation in pediatrics. The aim of this study was to evaluate the effects of LVAD on right ventricular (RV) function in children. We retrospectively reviewed clinical and echocardiographic data of children who underwent Berlin Heart EXCOR LVAD focusing on RV function before and after implantation (1, 3, and 6 month follow-up). An isolated LVAD was used in 27 patients. Median age was 11 months (interquartile range [IQR]: 5-24 months), with a median weight of 6.3 kg (IQR: 5-9 kg). Median time on ventricular assist device (VAD) support was 147 days (IQR: 86-210 days). Twenty patients were successfully bridged to orthotopic heart transplantation (OHT) (74%), six patients died (22%), and also heart function recovered in one patient (4%). Before LVAD implantation, nine patients (33%) showed a RV fractional area change (RVFAC) less than or equal to 30%. After implantation, mean RVFAC increased up until the 3 month follow-up (43.13%; p = 0.033) and then slightly decreased. In a subgroup of 18 patients, the average strain value increased after the 1 month follow-up (p = 0.022). Right ventricular failure developed in 33% of patients before the 1 month follow-up, and 7.4% experienced RVF at the 6 month follow-up. No patient required biventricular assist device (BiVAD). In our population, pulsatile-flow LVAD in children allows optimal RV decompression and function post-LVAD as measured by improvement in RV function at echo particularly at 1 and 3 month follow-up. At long-term follow-up, the beneficial effects of LVAD on RV function seem to be reduced as signs and symptoms of late RVF may develop in some patients despite LVAD support.

Since the spread of COVID-19, pediatric patients were initially considered less affected by SARS-COV-2, but current literature reported subsets of children with multisystem inflammatory syndrome (MIS-C). This study aims to describe the cardiac manifestation of SARS-COV-2 infection in a large cohort of children admitted to two Italian pediatric referral centers. Between March 2020 and March 2021, we performed a cardiac evaluation in 294 children (mean age 9 ± 5.9 years, male 60%) with active or previous SARS-COV-2 infection. Twenty-six showed ECG abnormalities: 63 repolarization anomalies, 13 Long QTc, five premature ventricular beats, two non-sustained ventricular tachycardia, and one atrial fibrillation. In total, 146 patients underwent cardiac biomarkers: NT-proBNP was elevated in 57, troponin in 34. An echocardiogram was performed in 98, showing 54 cardiac anomalies: 27 left-ventricular dysfunction, 42 pericarditis, 16 coronaritis. MIS-C was documented in 46 patients (mean age 9 ± 4.8 years, male 61%) with cardiac manifestations in 97.8%: 27 ventricular dysfunctions, 32 pericarditis, 15 coronaritis, 3 arrhythmias. All patients recovered, and during follow-up, no cardiac anomalies were recorded. Our experience showed that cardiac involvement is not rare in children with SARS-COV-2, and occurred in almost all patients with MIS-C. However, patients’ recovery is satisfactory and no additional events were reported during FU.

Right ventricular (RV) evaluation represents one of the major clinical tasks in the follow-up of repaired tetralogy of Fallot patients (rToF) with pulmonary valve regurgitation, as both severe RV dilatation and dysfunction are key factors in defining the need of pulmonary valve replacement. The aim of our study was to report the diagnostic accuracy of echocardiography in the identification of rToF patients with severely dilated and/or depressed RV as compared to cardiac magnetic resonance (CMR). Among our patients with rToF, a subgroup of 95 (17.6 ± 6.8 years; 60% male), who underwent right ventricular qualitative and quantitative evaluation with CMR following echocardiographic suspicion of severe dilation/dysfunction, were included in the analysis. When comparing echocardiographic RV functional parameters to CMR findings, we found no association between CMR-ejection fraction (EF) and either tricuspid annulus plane systolic excursion (TAPSe) nor tissue Doppler systolic tricuspid excursion velocity (all p = ns). In contrast RVFAC was strongly associated with CMR-EF (r = 0.44; p

Aims Right ventricular (RV) apical (RVA) pacing can induce left ventricular (LV) dyssynchrony, remodeling, and dysfunction in children with complete atrioventricular block (CAVB). We compared the functional outcome of RVA with RV alternative pacing sites (RVAPS), including para-Hisian, septal, and outflow tract sites. Methods This is a single-center, retrospective study. Data were collected before pacemaker implantation (transvenous leads), postoperatively, at 6 months, and at 1–2–3–4 years. Electrocardiogram evaluation included QRS duration, axis, QTc/JTc, and QTc dispersion. Echocardiographic evaluation included 2-D/3-D assessment of ventricular dimensions (Z-score of LV end-diastolic dimension), function (ejection fraction), and synchrony. Results From 2009 to 2015, 55 patients with CAVB, aged 3–17 years, with or without other congenital heart defects, underwent RVAPS (30 patients, median age 11 years) or RVA (25 patients, median 12 years). All leads were positioned into the septum. Before implantation, no significant differences in parameters were observed, except for higher Z-score in RVAPS than in RVA. After implantation, at a median follow-up of 2.5 (range 1–6) years, the two groups showed no significant differences in LV dimensions, contractility, and synchrony. QRS intervals of RVAPS were significantly shorter than RVA. Clinical status was good and contractility/synchrony indexes were normal or adequate in all patients. Conclusions In pediatric patients, RVAPS and RVA showed no significant differences in LV dimensions, contractility, and synchrony. Preimplantation dilated patients showed LV reverse remodeling. RVAPS demonstrated shorter QRS intervals. Therefore, septal pacing sites, either RVA or RVAPS, seem to determine good contractility and synchrony at a mid-term follow-up.

On 7 October 2012, the Philippine Government and the Moro Islamic Liberation Front agreed to the framework of a peace deal (signed on 15 October 2012) with the aim to pave the way for enduring peac...

Aims Recently, voltage gradient mapping of Koch's triangle to find low-voltage connections, or 'voltage bridges', corresponding to the anatomic position of the slow pathway, has been introduced as a method to ablate atrioventricular nodal reentry tachycardia (AVNRT) in children. Thus, we aimed to assess the effectiveness of voltage mapping of Koch's triangle, combined with the search for the slow potential signal in 'low-voltage bridges', to guide cryoablation of AVNRT in children. Methods and results From June 2015 to May 2016, 35 consecutive paediatric patients (mean age 12.1 ± 4.5 years) underwent 3D-guided cryoablation of AVNRT at our Institution. Fifteen children were enrolled as control group (mean age 14 ± 4 years). A voltage gradient mapping of Koch's triangle was obtained in all patients, showing low-voltage connections in all children with AVNRT but not in controls. Prior to performing cryoablation, we looked for the typical 'hump and spike' electrogram, generally considered to be representative of slow pathway potential within a low-voltage bridge. In all patients the 'hump and spike' electrogram was found inside bridges of low voltage. Focal or high-density linear lesions, extended or not, were delivered guided by low-voltage bridge visualization. Acute success rate was 100%, and no recurrence was reported at a mean follow-up of 8 ± 3 months. Conclusions Voltage gradient mapping of Koch's triangle, combined with the search for the slow potential signal in low-voltage bridges, is effective in guiding cryoablation of AVNRT in paediatric patients, with a complete acute success rate and no AVNRT recurrences at mid-term follow-up.

Aim Use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) to prevent sudden cardiac death is increasing. Few data exist on S-ICD in young patients. We report preliminary data from a multicenter European registry of paediatric and young adult patients who underwent S-ICD implantation Methods Observational, prospective, non-randomized, standard-of-care study on S-ICD implantation/follow-up in young patients with inherited arrhythmias (IA), cardiomyopathies, and congenital heart defects (CHD). Results 29 patients (12 CHD, 14 Cardiomyopathies, and 3 IA), mean age 17±6 years, 13 of them Conclusion These preliminary results of a multicenter European paediatric registry suggest that S-ICD is safe and effective with low rates of inappropriate shocks. Improvement of implantation techniques seems associated with better outcome.

Background Heart failure is becoming the most prominent cause of death among patients with Duchenne Muscular Dystrophy (DMD) and end-stage cardiomyopathy (CMP). Implantation of left ventricular assist devices (LVAD) as destination therapy (DT) in this group of patients is still matter of debate. No current data are available on long-term follow- up of young patients. Purpose The aim of this study was to evaluate the long-term outcome of LVAD in DMD end stage heart failure (HF) compared to a group treated optimal medical treatment (OMT) with inotropes Methods All patients affected by DMD patients presenting with end-stage HF receiving OMT or LVAD have been reviewed. All data about characteristics of HF at presentation including assessment of nutritional status and respiratory function, left ventricular ejection fraction, brain natriuretic peptide, serum sodium, in-hospital treatment and long term follow up have been collected. OMT group was constituted by 4 patients matching implantation VAD criteria but not eligible or refusing treatment. Survival was represented by Kaplan Meier analysis. Results A total of 12 DMD patients with end-stage CMP were considered for this analysis. 8 have been implanted with LVAD during the period from 2011 until mid-2017 and compared with 4 treated with OMT. Mean systolic pressure was 103 versus 91 mmHg in those not receiving LVAD (p=0.2), and left ventricular ejection fraction at the time of presentation was 16‰ for LVAD group and 22‰ for the second group (p=0.1). LVADs improved survival throughout follow-up for patients undergoing baseline inotropic infusions (P=0.0014); for the LVAD group versus the OMT group, 1-month survival was 100‰ and 67‰ respectively and 2-month survival was 100‰ versus 0‰. For LVAD group survival was 86‰ at one year, 71‰ at 2 years and 48‰ at 5 years from implantation. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD (log rank Conclusions LVAD improved outcomes in patients with LVAD when compared to those without. Long-term follow-up was similar to DT LVAD adult population. Further studies are necessary to confirm these data.

BACKGROUND Psychological distress is a major issue among survivors of women’s cancer who face numerous barriers to accessing in-person mental health treatments. Mobile phone app–based interventions are scalable and have the potential to increase access to mental health care among survivors of women’s cancer worldwide. OBJECTIVE This study aimed to evaluate the acceptability and preliminary efficacy of a novel app-based intervention with phone coaching in a sample of survivors of women’s cancer. METHODS In a single-group, pre-post, 6-week pilot study in the United States, 28 survivors of women’s cancer used iCanThrive, a novel app intervention that teaches skills for coping with stress and enhancing well-being, with added phone coaching. The primary outcome was self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale). Emotional self-efficacy and sleep disruption were also assessed at baseline, 6-week postintervention, and 4 weeks after the intervention period. Feedback obtained at the end of the study focused on user experience of the intervention. RESULTS There were significant decreases in symptoms of depression and sleep disruption from baseline to postintervention. Sleep disruption remained significantly lower at 4-week postintervention compared with baseline. The iCanThrive app was launched a median of 20.5 times over the intervention period. The median length of use was 2.1 min. Of the individuals who initiated the intervention, 87% (20/23) completed the 6-week intervention. CONCLUSIONS This pilot study provides support for the acceptability and preliminary efficacy of the iCanThrive intervention. Future work should validate the intervention in a larger randomized controlled study. It is important to develop scalable interventions that meet the psychosocial needs of different cancer populations. The modular structure of the iCanThrive app and phone coaching could impact a large population of survivors of women’s cancer.

End-stage dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in patients with Duchenne Muscular Dystrophy (DMD). No studies are available on the effect of ivabradine on long-term outcomes in end-stage DMD/DCM.We prospectively enrolled a cohort of end-stage DMD/DCM patients with LV ejection fraction40%, on chronic HF treatment with an ACE inhibitor referred consecutively from 2012 to 2017 to Bambino Gesù Children's Hospital. In each patient, before starting HRR strategy and after 1 year, we collected medical records comprehensive of clinical, demographic and imaging parameters, BNP levels, neurological and respiratory assessment.Twenty male patients with DMD/DCM with a mean age of 15.0 ± 3.5 (13-19 IQR) years were enrolled and divided into 2 groups according to ivabradine therapy. This group showed a higher incidence of MACEs compared to others in treatment with ivabradine (87.5% vs 12.5%, p = 0.025). At Kaplan Meier survival analysis curves, the rate free from MACEs was higher in patients treated with ivabradine (log rank p = 0.017). At multivariate Cox regression analysis, ivabradine therapy was an independent predictor of freedom from MACEs (H.R. 0.078, 95% CI 0.007-0.877, p = 0.039).HRR strategy, whether achieved by beta blockers alone or in combination with ivabradine, seemed to be effective in reducing the incidence of acute adverse events, reaching optimal target heart rate and improving left ventricular function in DMD/DCM patients.

The new Advisor HD Grid Sensor Enabled mapping catheter (Abbott Medical Italia S.p.A., Agrate Brianza, Italy) has been recently used in different clinical settings. This new multipolar catheter with small electrodes and very short inter-electrode space has been proved to be effective and safe in left atrial mapping for atrial fibrillation ablation procedures,1 as well as for right ventricle premature ventricular contraction mapping2 and for left ventricle epicardial mapping.3 In the last years, different authors have described 3D voltage mapping of the Koch triangle in order to find low-voltage bridges as targets for a successful transcatheter ablation (TCA) of the slow pathway in children.4 Although this new strategy seems to be very promising, mapping can be difficult, operator-dependent, and time-consuming.

Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms.

Objectives: IgMs that inactivate oxidation specific epitopes (IgMOSE) on phospholipids such as low density lipoprotein (LDL) were shown to confer athero-protection. We developed a 24 antibodies mass cytometry panel (CyTOF) to identify the human B cell subtype producing IgM to malondialdehyde modified LDL (IgMMDA-LDL), a predominant IgMOSE in humans. We also utilized humanized mice model to characterize a role of CD24 mediated IgM production. Methods: Peripheral blood mononuclear cells from healthy donors and subjects with coronary artery disease (CAD) undergoing quantitative coronary angiography were used to perform high dimensional analysis using CyTOF, RNAseq and Abseq as well as adoptive transfer into humanized mice model. Results: CD20+CD27+IgM+ cells (B27+IgM+) spontaneously produced IgM and produced IgMMDA-LDL in response to MDA stimulation when injected into humanized mice; an effect significantly augmented in B27+IgM+ cells with high expression of CD24 (B27+IgM+CD24hi). CD24 expression also enhanced splenic and bone marrow trafficking of B27+IgM+ cells. Blocking CD24 with a mAb reduced CCR6 expression, increased CCL20-induced CCR6 internalization and impaired migration to the spleen leading to lower IgM production. Lastly, single cell protein and transcriptome sequencing of PBMCs from 60 CAD subjects revealed enhanced CCR6 and IgM signaling in B27+IgM+CD24hi cells in subjects with low compared to high CAD severity. Conclusions: Identification of IgMMDA-LDL-producing cells in humans has the potential to allow for the development of therapeutics aimed at cellular targeting that may allow for enhancing production of IgM to the many OSE produced during inflammatory states such as atherosclerosis.

Objective: IL-6 is implicated in the development of coronary artery disease (CAD), autoimmune (AI) disorders, and cytokine storm syndrome (CSS). IL-6 inhibitors are effective in treating AI disorders and are being tested for CAD and CSS. While some studies have reported on IL-6-induced STAT signaling in humans, a comprehensive map of IL-6 signaling in human immune cells is currently lacking. We developed a 32-antibody custom mass cytometry (CyTOF) panel to characterize IL-6 signaling across all major human immune cell subsets, and applied it to identify IL-6-induced immune signatures linked with unstable atherosclerotic plaque. Methods: Blood cells from healthy donors and CAD subjects undergoing virtual histology-intravascular ultrasound imaging were stimulated with IL-6, stained and ran in CyTOF. Unsupervised analytical tools (SPADE, UMAP, and Leiden clustering) were used to identify immune cell subsets and IL-6-induced intracellular phosphorylation status. Results: IL-6 induced STAT1 and STAT3 activation in CD4 and CD8 naïve T cell subsets and CD4 memory T subsets. Notably, we identified that IL-6 also activates STAT5 within the CD4 and CD8 naïve T subsets. IL-6 induced a much more robust activation of STAT1 as compared to STAT3 and STAT5. Other cell types such as CD14+ monocytes, and CD11c+ and CD123+ dendritic cells also showed IL-6-induced STAT activation. IL-6-induced phosphorylation of STAT1 and STAT3 in a novel PD-1+CD27−CD127lowCD4+ effector memory T cell subtype was associated with higher CAD burden and unstable plaque features. Conclusions: Findings are significant for mechanistic insights into IL-6-induced inflammation and may enable discovery of new approaches to reduce inflammation in CAD and other pathologies.

Purpose We aim to evaluate clinical outcomes, echocardiographic changes, heart rate (HR) modifications and side effects in children with dilated cardiomyopathy (DCM) and chronic heart failure (HF) treated by high dosage of carvedilol. Methods We prospectively enrolled pediatric patients with DCM and ventricular dysfunction (EF 20% from baseline. Conventional treatment should be started from at least 1 month. Initial dosage of carvedilol was 0.1 mg/kg/day, up-titrated every 2 weeks to a maximum dose of 1 mg/kg/day. All data were compared to an historical control group treated with low dose of carvedilol or without beta-blockers. Data were collected before and after one year of maximum tolerated treatment. Results 65 patients (58% male) were enrolled, mean age was 13.4 +/- 9 years. 72 patients (48% male) were enrolled in the control group, mean age was 3.9 +/- 3.7. Mean duration of treatment was 50 months. HR reduction and EF improvement were statistically significant after treatment (mean HR reduction was 23%, p Conclusion High dosage of carvedilol up-titrated to achieve a reduction of heart rate of 20%, in addition to standard therapy, significantly improve ventricular function and survival in pediatric patients with DCM.

Purpose Assess the long term cardiovascular outcomes of heart rate reduction strategy (HRR) using ivabradine in children with chronic heart failure (HF). Background Chronic heart failure (HF) due to dilated cardiomyopathy (DCM) remains a significant medical challenge in pediatric population. There is paucity of evidence about pharmacological management of this population. Methods We conducted a retrospective cohort study including all children with end stage dilated cardiomyopathy (DCM) with LV function Results 72 children were included in the study and 23 treated with HRR strategy. After 1 year, HRR strategy was able to reduce heart rate [from 109.2 ± 26.4 bpm to 79.04 ± 18.8 bpm (p Conclusion Treatment with HRR strategy, in addition to standard HF therapy, seemed to be effective in reducing the incidence of acute adverse events and improving ventricular function in children with DCM and chronic HF.

Purpose The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy (DMD-DCM). Methods We collected data of end stage DMD-DCM patients who were implanted with LVAD in our center (group 1) and the ones in regular follow-up because not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD heart failure (HF) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. All data during long-term follow-up were recorded including echocardiography, ECG examination, laboratory blood tests, BNP dosing and assessment of nutritional status and respiratory function. Survival of the groups was represented by Kaplan Meier analysis and compared by log rank. Results A total of eight DMD-DCM patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The most prominent complications were bleeding and infections with one episode of acute heart failure that was successfully treated. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After one year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) together with a significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank Conclusion Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function. LVAD improved outcomes in patients with LVAD when compared to those without.

The post-surgical history of repaired congenital heart disease (rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden death. Electrical myocardial abnormalities could be a substrate for malignant ventricular arrhythmias.146 patients with TOF or other rCHD involving a subpulmonary right ventricle, considered to be at high arrhythmic risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM). Maps showed endocardial scars (0.5mV) in all cases, mainly involving the RV outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved. Total scar extension, expressed as % of total endocardial area, was significantly higher in patients with QRS ≥180ms [4.5% (±2.5) vs 2.8% (±2.4), p=0.014], left and right ventricular systolic dysfunction [4.5% (±3.2) vs 2.8% (±2.3), p=0.016 and 3.5% (±3.0) vs 2.6% (±1.9), p=0.03, respectively], premature ventricular contractions (PVCs) [3.2% (±2.6) vs 2.2% (±1.8), p0.05], exercise-induced PVCs [3.8% (±2.4) vs 2.6% (±2.2), p=0.01], previous shunt [4.0% (±2.7) vs 2.6% (±2.2), p=0.01] and reintervention [4.2% (±3.2) vs 2.6% (±2.0), p=0.008]. Scar size also showed a positive correlation with duration of post-surgical follow-up (ρ=0.01), age at correction (ρ=0.01) and absolute QRS duration (ρ=0.05).Patients with rCHD involving the right ventricle show electrical scars with variable distribution, not necessarily matching with sites of surgical lesions. Scar extension correlates with some of the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS. Thus EVM could be considered an additional tool in the assessment of risk stratification in this particular population.

Background Transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal reentry tachycardia (AVNRT) in children. Nevertheless, atrioventricular nodal slow-pathway conduction may recur after an acutely successful procedure. The aim of this study was to evaluate the long-term outcome of acutely successful AVNRT cryoablations in pediatric patients in case of focal cryolesion and in case of need for High-Density Linear Lesion (HDLL) cryoablation due to focal failure. Methods Sixty-nine consecutive pediatric patients (30 males, mean age 12.4 ± 3.2 years; range: 5.4-18.0 years) underwent 3D-guided cryoablation for AVNRT at our institution from July 2013 to November 2014. When a focal cryoablation was acutely unsuccessful, a 3D-guided HDLL was created delivering multiple overlapping cryolesions/cryoenergy applications from the ventricular side of the tricuspid annulus to the atrial side, including the site of focal cryoablation if transiently successful. Results No permanent cryoablation-related complications occurred. Acute success rate was 98.5% (68 out of 69): in 55.9% (38 out of 68) with focal-lesion and in 44.1% (30 out of 68) with HDLL. Mean follow-up was 25.3 months and AVNRT recurrence rate was 13.2% (nine out of 68): 5.2% (two out of 38) with focal lesion and 23.3% (seven out of 30) with HDLL (P = 0.036). Conclusions In cryoablation of AVNRT in children, the need for a more aggressive protocol (HDLL), due to the failure of focal ablation, is strictly related to higher recurrence rates. Indeed, AVNRT recurrences after cryoablation in children seem to be due to a larger and deeper substrate rather than due to the type of energy used.

In OHT recipients, pathologic evaluation of the heart during acute rejection can show involvement of both the conduction system and the myocardium. We here describe the cases of a 9-year-old male with DCM and a 13-year-old female with RCM, who developed third-degree PAVB associated with acute rejection 36 months and 24 months after OHT, respectively. We conclude that PAVB could be considered an early sign of acute rejection after OHT in children who exhibit post-transplantation presyncope or syncope.

Background The etiological diagnosis of syncope and/or palpitations in children is often challenging. However, when noninvasive conventional examinations are inconclusive, the subcutaneous miniaturized implantable loop recorder (ILR) is recommended. The aim of our study was to evaluate the efficacy of miniaturized cardiac implantable devices in the early diagnosis of arrhythmias in children ≤6 years. Methods From March 2014 to May 2015, 21 patients (median age 5 years) underwent implantation of miniaturized ILR at our Institution after a complete cardiac work up. Median follow-up was 10 months. Results One patient underwent device removal for pocket infection and one needed a pocket revision. Eleven (52%) patients did not show any symptom and/or arrhythmia. Eight patients experienced symptoms during ILR monitoring: six had no electrocardiographic abnormalities, two had significant sinus pauses. Two patients had significant arrhythmias without symptoms and in one of these a pacemaker was implanted. The overall diagnostic yield was 47%. Conclusions Miniaturized ILR could be very useful to make a diagnosis and to decide future management strategies in small patients with undefined symptoms or severe cardiac diseases. Considering its characteristics, miniaturized ILR could start a new era in the diagnosis and follow-up of young patients with symptomatic and/or malignant arrhythmias.

We report a case of a 10-year-old female patient who survived ring-sling complex without surgery. The patient had congenital wheezing from the neonatal period and was treated after a tentative diagnosis of infantile asthma. The patient suffered from allergy and was hospitalized several times due to severe wheezing, and when she was 22 months old, she was diagnosed with ring-sling complex. We used a segmental 4 mm internal diameter of the trachea for 3-dimensional computed tomography (3D-CT). Bronchial asthma is considered an exacerbating factor in infantile period and frequently required treatment with bronchodilator. After the age of 10, the patient had recurrent breathing difficulties during physical activity and during night time, and this condition was assessed to be related to the pressure from the blood vessel on the ring. We repeated the 3D-CT evaluation later and discovered that the internal diameter of the trachea had grown to 5 mm. Eventually, patient's breathing difficulties disappeared after the treatment of bronchial asthma and restriction of physical activities. Our patient remained in stable condition without undergoing any surgical procedures even after she passed the age of 10.

We report here a very rare case of de novo inversion-duplication chromosomal abnormality with a pure 3qter duplication syndrome. Interestingly, the 3q duplication includes an overlap of the syndromes critical region. Although there have only been 9 cases of this syndrome reported in the past, our patient had more severe neurological abnormalities than anticipated. In this regard, we have gathered the 3q chromosomal duplication abnormalities known to cause pure 3q duplication syndrome to date as a reference for comparisons and we discuss the particulars of our case.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

Background: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability. Case presentation: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (pArg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far. Conclusions: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.