Health-related quality of life among paediatric patients with coarctation of the aorta: an observational study.

Advancements in early diagnosis and paediatric cardiac surgery have improved the long-term survival of patients with congenital heart disease, necessitating a thorough assessment of their health-related quality of life (HRQoL). This study aimed to assess HRQoL in paediatric patients with coarctation of the aorta (CoA) (both as reported by patients and caregivers), and to evaluate associated factors. Patients aged 5-18 years diagnosed with CoA and their parents were enrolled at Bambino Gesù Children's Hospital between September 2016 and December 2017. Socio-demographic characteristics were recorded using a family form, and the Pediatric Quality of Life Inventory (PedsQL) 3.0 cardiac module was used to evaluate HRQoL. Clinical data were retrieved from medical chart reviews. In this observational study, sixty-five pediatric patients (39 males, median [IQR] age 12 [9-14]) with CoA and their parents (65 mothers and 65 fathers) were enrolled. These patients exhibited overall good HRQoL. Mothers reported significantly lower total HRQoL scores compared to patient self-reports (p = .037), as well as treatment anxiety (p = .033), and cognitive problems (p = .021). Pediatric patients with CoA perceived their HRQoL better than their mothers did. Female sex and older age were associated with lower HRQoL scores.

Trans-jugular approach for safe and successful cryoablation of para-Hisian/anterior-septal, anterior, and anterior-lateral accessory pathways in children.

BACKGROUND: Cryoablation of APs localized near the atrioventricular (AV) junction is a well-established ablation strategy in children, and it has proved to be very safe. However, recurrence rates remain considerable for specific accessory pathway (AP) localizations. The aim of this retrospective study was to evaluate the efficacy and safety of a trans-jugular approach for cryoablation of right anterior, anterior-lateral, and anterior-septal APs in children, as compared to the conventional femoral approach. METHODS: From June 2019 to November 2023, 24 consecutive patients (mean age 13.2 ± 4.6, 12 males (50% of total cohort)) with right anterior-lateral, anterior, and anterior-septal/para-Hisian APs underwent 3D non-fluoroscopic transcatheter cryoablation through the right jugular vein at our Institution. Ablation results were compared with 24 patients for whom a conventional trans-femoral approach was used. RESULTS: Acute procedural success rate was 100% (n = 24/24), with a non-statistically significant difference as compared to the control group (100% vs. 83%, p = 0.1). During follow-up (1.1 years, interquartile range 0.6-1.3), one patient (4%) had a recurrence in the trans-jugular group, as opposed to eight (38%) in the control group (p = 0.006). No permanent complications occurred. CONCLUSIONS: 3D cryoablation of right anterior-lateral, anterior, and anterior-septal/para-Hisian APs in children using a trans-jugular approach is extremely effective and safe, resulting in higher chronic success rate compared to the conventional femoral approach.

Cardiopulmonary Exercise Testing after Surgical Repair of Tetralogy of Fallot-Does Modality Matter?

BACKGROUND: Despite a successful repair of tetralogy of Fallot (rToF) in childhood, residual lesions are common and can contribute to impaired exercise capacity. Although both cycle ergometer and treadmill protocols are often used interchangeably these approaches have not been directly compared. In this study we examined cardiopulmonary exercise test (CPET) measurements in rToF. METHODS: Inclusion criteria were clinically stable rToF patients able to perform a cardiac magnetic resonance imaging (CMR) and two CPET studies, one on the treadmill (incremental Bruce protocol) and one on the cycle ergometer (ramped protocol), within 12 months. Demographic, surgical and clinical data; functional class; QRS duration; CMR measures; CPET data and international physical activity questionnaire (IPAQ) scores of patients were collected. RESULTS: Fifty-seven patients were enrolled (53% male, 20.5 ± 7.8 years at CPET). CMR measurements included a right ventricle (RV) end-diastolic volume index of 119 ± 22 mL/m2, a RV ejection fraction (EF) of 55 ± 6% and a left ventricular (LV) EF of 56 ± 5%. Peak oxygen consumption (VO2)/Kg (25.5 ± 5.5 vs. 31.7 ± 6.9; p < 0.0001), VO2 at anaerobic threshold (AT) (15.3 ± 3.9 vs. 22.0 ± 4.5; p < 0.0001), peak O2 pulse (10.6 ± 3.0 vs. 12.1± 3.4; p = 0.0061) and oxygen uptake efficiency slope (OUES) (1932.2 ± 623.6 vs. 2292.0 ± 639.4; p < 0.001) were significantly lower on the cycle ergometer compared with the treadmill, differently from ventilatory efficiency (VE/VCO2) max which was significantly higher on the cycle ergometer (32.2 ± 4.5 vs. 30.4 ± 5.4; p < 0.001). Only the VE/VCO2 slope at the respiratory compensation point (RCP) was similar between the two methodologies (p = 0.150). CONCLUSIONS: The majority of CPET measurements differed according to the modality of testing, with the exception being the VE/VCO2 slope at RCP. Our data suggest that CPET parameters should be interpreted according to test type; however, these findings should be validated in larger populations and in a variety of institutions.

An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there are limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic patients with CPVT with and without ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with ICD (31.1%) and 162 without ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in the no ICD group and in those not on optimal medical therapy. Patients with ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

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

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

Congenital Heart Defects in Patients with Molecularly Confirmed Sotos Syndrome.

Sotos syndrome is an autosomal dominant condition characterized by overgrowth with advanced bone age, macrodolicocephaly, motor developmental delays and learning difficulties, and characteristic facial features caused by heterozygous pathogenetic variants in the NSD1 gene located on chromosome 5q35. The prevalence of heart defects (HDs) in individuals with Sotos syndrome is estimated to be around 15-40%. Septal defects and patent ductus arteriosus are the most commonly diagnosed malformations, but complex defects have also been reported. The aim of our study was to analyze the prevalence of HD, the anatomic types, and the genetic characteristics of 45 patients with Sotos syndrome carrying pathogenetic variants of NSD1 or a 5q35 deletion encompassing NSD1, who were followed at Bambino Gesù Children's Hospital in Rome. Thirty-nine of the forty-five patients (86.7%) had a mutation in NSD1, while six of the forty-five (13.3%) had a deletion. Most of the patients (62.2%, 28/45) were male, with a mean age of 14 ± 7 years (range 0.2-37 years). A total of 27/45 (60.0%) of the patients had heart defects, isolated or combined with other defects, including septal defects (12 patients), aortic anomalies (9 patients), mitral valve and/or tricuspid valve dysplasia/insufficiency (1 patient), patent ductus arteriosus (3 patients), left ventricular non-compaction/hypertrabeculated left ventricle (LV) (4 patients), aortic coarctation (1 patient), aortopulmonary window (1 patient), and pulmonary valve anomalies (3 patients). The prevalences of HD in the two subgroups (deletion versus intragenic mutation) were similar (66.7% (4/6) in the deletion group versus 58.91% (23/39) in the intragenic variant group). Our results showed a higher prevalence of HD in patients with Sotos syndrome in comparison to that described in the literature, with similar distributions of patients with mutated and deleted genes. An accurate and detailed echocardiogram should be performed in patients with Sotos syndrome at diagnosis, and a specific cardiological follow-up program is needed.

Transvenous lead advancement in pediatric pacing to overcome growth-induced lead straightening and stretching.

BACKGROUND: The stretching of the lead caused by somatic growth may lead to complications (dislodgement, fracture, failure) of transvenous leads implanted in pediatric patients. Atrial loop and absorbable ligatures may prevent it. Periodical lead advancement with lead pushing from the pocket may be an option to growth-induced stretching. Our aim was to analyze retrospectively the outcome of periodical transvenous lead advancement in children with pacemaker (PM). METHODS: A procedure of lead advancement was performed in patients with a single-chamber PM implanted for isolated congenital complete atrioventricular block or sinus node dysfunction with growth-induced lead straightening/stretching. The PM pocket was opened, the lead was released from subcutaneous adherences and was gently advanced to shape again a loop/semi-loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are described as median (25th-75th centiles). RESULTS: 14 patients with 13 VVIR and 1 AAIR PM implanted at 6.8 (5.9-8.0) years of age, 23 (19-26) kg, 118 (108-124) cm, underwent 30 advancement procedures, 1.5 (1.0-2.3) per patient, during follow-up [45 (35-63) months]. Delta between procedures was: 18 (14-25) months, 11 (7-13) cm, 6 (4-9) kg; 90% of leads were successfully advanced without complications. Three unsuccessful procedures occurred with longer times [30 (14-37) months]. Electrical lead parameters did not show significant differences pre-/post-procedures. CONCLUSION: the advancement of transvenous leads in children seems safe and effective. This procedure may be another possible choice to preserve transvenous lead position and function until growth has completed.

Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease.

Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.

Marginal zone B cells produce 'natural' atheroprotective IgM antibodies in a T cell-dependent manner.

AIMS: The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of 'poorly differentiated' T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis. METHODS AND RESULTS: We generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr-/- mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF/HC diet-induced Tfh. CONCLUSION: Our findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective 'natural' IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.

Inherited Arrhythmias in the Pediatric Population: An Updated Overview.

Pediatric cardiomyopathies (CMs) and electrical diseases constitute a heterogeneous spectrum of disorders distinguished by structural and electrical abnormalities in the heart muscle, attributed to a genetic variant. They rank among the main causes of morbidity and mortality in the pediatric population, with an annual incidence of 1.1-1.5 per 100,000 in children under the age of 18. The most common conditions are dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Despite great enthusiasm for research in this field, studies in this population are still limited, and the management and treatment often follow adult recommendations, which have significantly more data on treatment benefits. Although adult and pediatric cardiac diseases share similar morphological and clinical manifestations, their outcomes significantly differ. This review summarizes the latest evidence on genetics, clinical characteristics, management, and updated outcomes of primary pediatric CMs and electrical diseases, including DCM, HCM, arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), and short QT syndrome (SQTS).

[Management of postoperative arrhythmias in the tetralogy of Fallot: a literature review]. / Gestione delle aritmie cardiache dopo correzione chirurgica della tetralogia di Fallot: revisione della letteratura.

Tetralogy of Fallot (ToF) occurs in about 4 births/1000/year and represents about one tenth of all congenital heart diseases. Nowadays 86% of patients reach adulthood with corrective surgery. Before the 1980s, these patients were treated only with "surgical palliation", which consisted in the creation of a systemic to pulmonary artery shunt or a pulmonary valvulotomy, whereas after the introduction of extracorporeal circulation, corrective surgery is performed electively between 3 and 6 months of life. After repair patients during their life may develop hemodynamic lesions, including right ventricular outflow tract dysfunction, and arrhythmias which can occur in over 30% of cases. It is estimated that these patients present a risk of sudden death of 0.2%/year. Therefore, for the prevention and treatment of arrhythmic events, a periodic follow-up in specialized centres for adult congenital heart disease is mandatory, because most often arrhythmias are triggered by the presence of hemodynamic lesions, first of all pulmonary regurgitation.

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

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

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

Biallelic truncating variants in children with titinopathy represent a recognizable condition with distinctive muscular and cardiac characteristics: a report on five patients.

Background: Monoallelic and biallelic TTN truncating variants (TTNtv) may be responsible for a wide spectrum of musculoskeletal and cardiac disorders with different age at onset. Although the prevalence of heterozygous TTNtv is relatively high in the general population, cardiac phenotyping (mainly cardiomyopathies, CMPs) in biallelic titinopathy has rarely been described in children. Methods: We reviewed the medical records of pediatric patients with biallelic TTNtv and cardiac involvement. Clinical exome sequencing excluded pathogenic/likely pathogenic variants in major CMP genes. Results: Five pediatric patients (four male) with biallelic TTNtv were included. Major arthrogryposis multiplex was observed in four patients; no patient showed intellectual disability. At a cardiac level, congenital heart defects (atrial and ventricular septal defects, n = 3) and left ventricular non-compaction (n = 1) were reported. All patients had dilated cardiomyopathy (DCM) diagnosed at birth in one patient and at the age of 10, 13, 14, and 17 years in the other four patients. Heart rhythm monitoring showed tachyarrhythmias (premature ventricular contractions, n = 2; non-sustained ventricular tachycardia, n = 2) and nocturnal first-degree atrio-ventricular block (n = 2). Cardiac magnetic resonance (CMR) imaging was performed in all patients and revealed a peculiar late gadolinium enhancement distribution in three patients. HyperCKemia was present in two patients and end-stage heart failure in four. End-organ damage requiring heart transplantation (HT) was indicated in two patients, who were operated on successfully. Conclusion: Biallelic TTNtv should be considered when evaluating children with severe and early-onset DCM, particularly if skeletal and muscular abnormalities are present, e.g., arthrogryposis multiplex and congenital progressive myopathy. End-stage heart failure is common and may require HT.

Left ventricular endocardial activation maps during right ventricular pacing in pediatric patients.

BACKGROUND: Cardiac pacing from right ventricular (RV) sites may cause electromechanical ventricular dyssynchrony. Invasive and noninvasive mapping studies showed left ventricular (LV) activation sequence in adults. Aim of this study was to seek out the LV endocardial activation (LVEA) in pediatric patients who underwent RV pacing. METHODS: Single-center, prospective study conducted on pediatric patients who underwent left sided catheter ablation of accessory pathways with the Carto Univu mapping system. After successful ablation procedures, LVEA was recorded by the ablation catheter during sinus rhythm (SR) and during para-hisian (PHP), midseptum (MSP), and apical (RVAP) pacing. RESULTS: Seventeen patients, 13 males, aged 12 (10-15) years, registered LV activation maps and times (LVAT). SR showed significantly shorter LVAT than during pacing. LVAT of PHP was shorter than MSP, while there were not significant differences among PHP and MSP versus RVAP. In SR initial LV endocardial activation occurred in two midseptum sites, inferior-posterior and superior-anterior. During PHP, initial activation occurred at parahisian basal septum, rapidly followed by midseptum as in SR. During MSP and RVAP initial activation occurred at midseptum and apex, respectively. From all initial sites, the excitation spreads toward the base of the lateral LV free wall. A mild linear correlation was found between QRS duration and LVAT for MSP and for PHP. CONCLUSIONS: In pediatric patients LVEA maps during RV pacing showed that the shortest LVAT was obtained with PHP. The LV activation pattern seemed similar in sinus rhythm, PHP and MSP, from midseptum to LV lateral base.

Autosomal Recessive Long QT Syndrome: Clinical Aspects and Therapy.

The autosomal recessive (AR) form of Long QT Syndrome (LQTS) is described both associated with deafness known as Jervell and Lange-Nielsen (JLN) syndrome, and without deafness (WD). The aim of the study is to report the characteristics of AR LQTS patients and the efficacy of the therapy. Data of all children with AR LQTS referred to the Bambino Gesù Children's Hospital IRCCS from September 2012 to September 2021were included. Three (30%) patients had compound heterozygosity and 7 (70%) had homozygous variants of the KCNQ1 gene, the latter showing deafness. Four patients (40%) presented aborted sudden cardiac death (aSCD): three with previous episodes of syncope (75%), the other without previous symptoms (16.6% of asymptomatic patients). An episode of aSCD occurred in 2/3 (66.7%) of WD and heterozygous patients, while in 2/7 (28%) JLN and homozygous patients and in 2/2 patients with QTC > 600 ms. All patients were treated with Nadolol. In 5 Mexiletine was added, shortening QTc and obtaining the disappearance of the T-wave alternance (TWA) in 3/3. Episodes of aSCD seem to be more frequent in LQTS patients with compound heterozygous variants and WD than in those with JLN and homozygous variants. Episodes of aSCD also appear more frequent in children with syncope or with QTc value > 600 ms, even on beta-blocker therapy, than in patients without syncope or with Qtc < 600 ms. However, our descriptive results should be confirmed by larger studies. Moreover, Mexiletine addition reduced QTc value and eliminated TWA.

Characterizing blood pressure trajectories in people living with HIV following antiretroviral therapy: A systematic review.

OBJECTIVES: The advent of antiretroviral therapy (ART) has reduced AIDS-related morbidity and mortality among people living with HIV (PLWH). Due to increased survival, PLWH have now been found to be at risk of chronic conditions related to ageing, such as cardiovascular disease (CVD). Hypertension is common in PLWH and is a major risk factor for the development of CVD. We conducted a systematic literature review to evaluate the research evidence on longitudinal blood pressure (BP) trajectories following ART initiation in PLWH. METHODS: We searched the following databases: PubMed, CINHAL, Scopus, and Web of Science (up to 15 March 2021) for peer-reviewed published studies that reported BP trajectories following ART initiation in PLWH. Three reviewers independently screened all studies by title and abstract. We included articles in English, published up to March 2021, that report office BP trajectories in PLWH initiating ART. A total of 10 publications met our inclusion criteria. Eight studies were prospective cohorts and two were retrospective. RESULTS: Nine out of 10 studies in the literature reported an increase in systolic BP (4.7-10.0 mmHg in studies with a follow-up range of 6 months to 8 years, and 3.0-4.7 mmHg/year in time-averaged studies). In addition, four out of 10 studies reported increases in diastolic BP (2.3-8.0 mmHg for a 6 month to 6.8-year follow-up range and 2.3 mmHg/year). CONCLUSION: Systolic BP consistently increases while diastolic BP changes are more heterogeneous following ART initiation in PLWH. However, the studies were highly variable with respect to population demographics, ART regimen and duration, and follow-up time. Nevertheless, given the risks of CVD complications, such as stroke, heart failure and myocardial infarction, associated with elevated BP, results highlight the importance of future research in this area. It will be important to better characterize BP trajectories over time, identify the most critical times for interventions to reduce BP, determine the long-term CVD consequences in PLWH with elevated BP, and understand how different ART regimens may or may not influence BP and CVD disease.

Differences in Physical Activity Levels between Healthy and Transplanted Children: Who Needs More Tips?

BACKGROUND: Advances in the medical-surgical field have significantly increased the life expectancy of patients undergoing solid organ transplantation but this exposes patients to long-term complications due to chronic therapies and changes in lifestyle. It is known that children affected by pathology tend to be more sedentary and inactivity represents a further risk factor for the onset of non-communicable diseases. The aim of the present study was to compare the lifestyle of two groups of young patients: one group of healthy subjects (HG) and one group of kidney or liver transplant recipients (TG). METHODS: Patients were asked to complete Physical Activity Questionnaire for Older Children (PAQ-C). RESULTS: A total of 104 subjects were recruited (50.9% male, mean age 12.8 ± 3.16 years old). No significant differences were observed in the final score between groups when comparing subjects based on health condition (Healthy 2.69 ± 0.65 vs. Transplant Group 2.42 ± 0.88), the intensity of sports activities (Competitive 2.82 ± 0.59 vs. Not Competitive 2.53 ± 0.7) or type of transplant (Liver 2.51 ± 0.91 vs. Kidney 2.16 ± 0.75). CONCLUSION: The results of this study showed a worrying reality: children are engaged in low levels of physical activity regardless of their health status and in general the level of activity does not reach the recommended values even in the absence of contraindications. So, it is necessary to encourage healthy children to practice more PA and to introduce PA prescriptions for transplanted children to prevent their health from deteriorating due to sedentariness.

Relapsing myocarditis following initial recovery of post COVID-19 vaccination in two adolescent males - Case reports.

Whilst there has been significant public health benefits associated with global use of COVID-19 spike protein vaccines, potential serious adverse events following immunization have been reported. Acute myocarditis is a rare complication of COVID19 vaccines and often it is self-limiting. We describe two cases experiencing recurrent myocarditis following mRNA COVID-19 vaccine despite a prior episode with full clinical recovery. Between September 2021-September 2022 we observed two male adolescents with recurrent myocarditis related to mRNA-based-COVID19 vaccine. During the first episode both patients presented with fever and chest pain few days after their second dose of BNT162b2 mRNA Covid-19 Vaccine (Comirnaty®). The blood exams showed increased cardiac enzymes. In addition, complete viral panel was run, showing HHV7 positivity in a single case. The left ventricular ejection fraction (LVEF) was normal at echocardiogram but cardiac magnetic resonance scanning (CMR) was consistent with myocarditis. They were treated with supportive treatment with full recovery. The 6 months follow-up demonstrated good clinical conditions with normal cardiological findings. The CMR showed persistent lesions in left ventricle 's wall with LGE. After some months the patients presented at emergency department with fever and chest pain and increased cardiac enzymes. No decreased LVEF was observed. The CMR showed new focal areas of edema in the first case report and stable lesions in the second one. They reached full recovery with normalization of cardiac enzymes after few days. These case reports outline the need of strict follow-up in patients with CMR consistent with myocarditis after mRNA-based-COVID19 vaccine. More efforts are necessary to depict the underlying mechanisms of myocarditis after SARS-CoV2 vaccination to understand the risk of relapsing and the long-term sequelae.

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.