INTRODUCTION:The Fontan procedure enables survival in individuals with univentricular physiology but is associated with progressive circulatory failure. Identifying predictors of adverse outcomes is essential to improve long-term management. This study evaluated five-year outcomes and baseline predictors of major events in a previously characterised paediatric and young adult Fontan cohort. METHODS:This retrospective longitudinal study included 51 patients (median age 18 years, interquartile range 11) who underwent comprehensive evaluation between 2018 and 2019, including echocardiography with atrial strain analysis and cardiopulmonary exercise testing. The composite outcome comprised death, heart transplantation listing, hospitalisation for heart failure, or conduit thrombosis. Univariable and multivariable logistic regression identified predictors of adverse outcomes. RESULTS:During a five-year follow-up, 7 patients (14%) met the composite outcome. Those with events had lower body mass index (19.8 kg/m2 [4.1] vs 16.9 [3.6]; p = 0.007), lower atrial conduit strain (10.95% [8.95] vs 2.8 [6.2]; p = 0.011), reduced peak oxygen uptake, and higher VE/VCO2 slope. In multivariable analysis, lower body mass index (OR 0.49, 95% CI 0.26-0.93; p = 0.028) and reduced atrial conduit strain (OR 0.70, 95% CI 0.51-0.96; p = 0.026) were independently associated with adverse outcome, with excellent model discrimination (AUC = 0.95). DISCUSSION:Both nutritional status and atrial functional parameters demonstrated a strong association with the outcome. Reduced atrial conduit strain, reflecting diastolic dysfunction, and lower body mass index, possibly reflecting myopenia or cachexia, identified higher-risk patients and potential areas for intervention. Routine assessment of atrial function and nutritional status should be integrated into clinical surveillance and risk stratification of the Fontan population.

Granulicatella elegans (G. elegans) is a fastidious, nutritionally variant streptococcus (NVS) that represents a rare but clinically significant cause of infective endocarditis (IE), particularly in patients with congenital heart disease (CHD). Diagnosis is frequently delayed owing to its specific culture requirements and an indolent, non-specific clinical presentation. We present a case of a six-year-old male with complex CHD who presented with an 11-day history of low-grade fever, anorexia, and asthenia. Seven months prior, he had undergone dental caries repair without antibiotic prophylaxis. Transthoracic echocardiography (TTE) showed no vegetations. After 18 days of incubation in enriched culture media, blood cultures yielded the identification of G. elegans. A diagnosis of possible IE was established per the modified Duke criteria. Treatment with ceftriaxone and gentamicin was initiated per the European Society of Cardiology (ESC) 2023 guidelines, subsequently switched to vancomycin due to hematological toxicity. The patient was discharged in stable condition and remained asymptomatic at a three-year follow-up. Comparison with five previously published pediatric cases of Granulicatella IE was made. G. elegans IE should be considered in any child with CHD and prolonged unexplained fever, even in the absence of classical echocardiographic findings.

BACKGROUND:Fasciculoventricular pathways (FVPs) are an uncommon cause of pre-excitation that can be mistaken for other more common accessory pathways in clinical practice. This case report highlights the key features of FVPs and their management. CASE SUMMARY:A 12-year-old male athlete was referred to the pediatric arrhythmia outpatient clinic with an asymptomatic pre-excitation on baseline routine electrocardiogram. Exercise stress test showed sustained pre-excitation throughout maximum heart rate. An electrophysiologic study documented an FVP and no inducible arrhythmia. No ablation was attempted, and the patient was discharged with return to play authorization without restrictions. DISCUSSION:Although they are not substrates for re-entrant tachycardia and are not associated with sudden death, diagnosis of FVPs is important to prevent unnecessary ablation and undue exercise restriction.

Cross-sectional cardiac imaging including cardiac computed tomography (CCT) and cardiac magnetic resonance imaging (CMR) allows three-dimensional imaging of intracardiac and extracardiac structures. This study was undertaken to better understand current European practice of pediatric cardiology cross-sectional imaging, in addition to how training is undertaken in different centers. A structured detailed 64-question survey focusing on cross-sectional imaging was circulated to all Imaging Working Group members of the 95 AEPC affiliated centers. Consultants from 42 centers (44

INTRODUCTION:Kartagener's syndrome is a rare subset of primary ciliary dyskinesia, a genetically heterogeneous disorder characterised by chronic sinusitis, bronchiectasis, and situs inversus. To our knowledge, the association of this syndrome with coarctation of the aorta (CoAo) and pulmonary hypertension (PH) has not been previously reported. CASE DESCRIPTION:We report the case of a 17-year-old female patient with situs inversus and CoAo surgically corrected at two months of age. At 12 years old, she developed a chronic cough, nasal congestion, and an estimated pulmonary artery systolic pressure (PASP) of 70 mmHg on echocardiography. Cardiac catheterisation revealed a pulmonary artery pressure of 58/10/24 mmHg with no gradient at the aortic isthmus. Thoracic CT scan demonstrated multiple bronchiectasis in the upper lobes bilaterally, despite normal pulmonary spirometry, plethysmography, and 24-hour oximetry. Genetic testing identified a pathogenic variant and a variant of uncertain significance of the DNAH5 gene, associated with primary ciliary dyskinesia. The patient was diagnosed with Kartagener's syndrome with PH and was started on inhaled glucocorticoids and chest physiotherapy. No episodes of pneumonia or acute bronchiectasis exacerbations were recorded. Annual lung function tests remained normal, and semiannual echocardiograms showed stable findings. A follow-up thoracic CT scan at 16 years of age revealed no progression of lung disease. At 16 years old, the patient developed significant physical activity limitation. Echocardiographic evaluation demonstrated right ventricular dilatation with reduced longitudinal function (TAPSE 15 mm, Z-score 4.4), suprasystemic PASP (120 mmHg), an eccentricity index of 2.3, normal left ventricular function, moderate pericardial effusion, and an NT-ProBNP level of 2292 pg/mL. Combined therapy targeting PH was initiated, including an endothelin receptor antagonist, a phosphodiesterase type 5 inhibitor, diuretics, and supplemental oxygen therapy. Significant clinical improvement was observed (WHO functional class IIIa to I), along with echocardiographic improvement (PASP reduced to 80 mmHg, TAPSE increased to 16 mm, resolution of pericardial effusion), and a marked decrease in NT-proBNP (171 pg/mL). CONCLUSIONS:The rapid progression of PH in this patient, despite normal lung function and unremarkable CT scan findings, is atypical for PH associated with lung disease. Extensive investigation for alternative causes of PH, including genetic testing, yielded negative results. A more aggressive treatment strategy for PH is currently being pursued.

Thymus-committed regulatory T cells (Tregs) are essential for immune homeostasis. Recent findings stress their heterogeneity, suggesting possible alternate routes for thymic Treg development with unique features in humans, namely the clear evidence of Treg commitment at the double-positive (DP) stage and the presence of a significant population of CD8 single-positive (SP) FOXP3pos Tregs. Here, we present a dedicated analysis strategy to a spectral flow cytometry-based study of thymus from children and aged adults (≥ 74-years-old), to further elucidate Treg development and heterogeneity in the human thymus. We applied an unsupervised analysis pipeline to data generated from 6 high-dimensional panels, taking advantage of a common backbone of 11 markers, and we were able to map thymocytes along T cell maturation stages. Generating UMAP and FlowSOM cluster coordinates from the backbone, we projected all other markers onto these, characterizing clusters with the information of all markers. Focusing this analysis on events inside a putative total Treg gate, we could portray rarer subsets of human thymic Tregs and investigate their trajectories using pseudotime analysis. We uncover clusters within human DP thymocytes uniquely expressing FOXP3 or CD25, a DP-branching trajectory towards a CD103posCD8SP Tregs endpoint, and define trajectories towards CD4SP Tregs, including towards a cluster of CXCR3posCD4SP Tregs, that may consist of thymic resident or recirculating Tregs, and do not expand in the elderly. Our flow cytometry approach separates Treg populations with likely distinct functions and facilitates the design of future studies to unravel the complexity of human regulatory T cells.

Infective endocarditis is rare and usually affects individuals with risk factors. Pasteurella species commonly causes skin infections, with systemic involvement being unusual. We report the first pediatric case of possible endocarditis caused by Pasteurella canis in a previously healthy boy, without congenital heart disease or prosthetic material, highlighting the importance of considering rare pathogens in atypical clinical presentations.

BACKGROUND:Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS:Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS:A total of 375 children (mean age, 8.1 +/- 5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS:In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks.

Background Prenatal diagnosis (PND) of aortic coarctation (AoCo) has been associated with a significant improvement in early results, but there is limited information on the long-term cardiovascular outcome. Methods We studied 103 patients with simple AoCo, operated in the neonatal period, with a median follow-up of 8,5 years (2 to 23,7 years), with 47% followed for over 10 years. PND was made in 35%. The primary aim was to determine the short and long-term cardiovascular impact of PND of AoCo. Results Neonates with PND had less preoperative neonatal complications, with only 2,8% incidence of a composite preoperative severe morbidity course, compared to 28% in the postnatal group. PND patients underwent surgery 8 days earlier and had a shorter length of stay in ICU. PND did not impact the incidence of post-operative complications. On the long-term, prevalence of hypertension, left ventricular hypertrophy and rate of recoarctation were not influenced by PND. The PND group had mean 24 h diastolic BP 9 mmHg lower and mean daytime diastolic BP 11 mmHg lower. In the final multivariable model, PND was the single independent variable correlating with daytime diastolic BP. Conclusion PND of AoCo effectively leads to a better pre-operative course with less pre-operative morbidity. We found no significant differences in immediate post-operative cardiovascular outcomes. A better initial course of patients with PND does not have a major long-term impact on cardiovascular outcomes, nevertheless, at late follow-up PND patients had lower diastolic BP values on ambulatory monitoring, which may have an impact on long-term cardiovascular risk.

The authors describe the case of a child with a history of relapsed acute lymphoblastic leukaemia with a giant intra-auricular lymphomatous mass, submitted to investigation by multiple imaging methods and biopsy.

Abstract Background and Aims Acute kidney injury (AKI) is a frequent complication in neonates and infants after congenital heart disease surgery, with great impact on morbidity and mortality. Peritoneal dialysis (PD) is the renal replacement therapy of choice, as it allows continuous gentle ultrafiltration with minimal impact on hemodynamic status. However, there is no standardized prescription. The present study aimed to describe our experience of using PD in the management of AKI after cardiac surgery in pediatric patients and the postoperative outcomes. Method Single-center cross-sectional study including 21 children undergoing cardiac surgery between 2017 and 2022, in a congenital heart disease reference center. Demographic and clinical data were collected from the electronic records. Results Of the 21 patients treated with PD, 11 were female. Mean age was 32 ± 45 days and median weight was 3.4 kg (IQR 0.5). All pregnancies had been full-term with a mean birth weight of 3.2 ± 0.3 kg. No congenital urinary tract anomalies had been previously documented. Previous history of AKI was present in 2 patients. Transposition of the great arteries was the most common surgical indication (52%). RACHS-1 score was ≥4 in 12 patients and median PRISM-IV score was 6.5% (IQR 6). Cardiopulmonary bypass was performed in 19 patients with a mean time of 181 ± 72 minutes and a mean aortic clamping time of 94 ± 29 minutes. All patients required inotropic support after cardiac surgery with ≥2 drugs, for 197 ± 136 hours. Median time with mechanical ventilation support was 126 hours (IQR 288) and median length of stay at the intensive care unit (ICU) was 9 days (IQR 15.3).The indications for PD initiation were anuria (66.7%), oliguria (23.8%) and fluid overload (9.5%). Median time between cardiac surgery and AKI diagnosis was 2.5 hours (IQR 8.8) and between AKI diagnosis and PD initiation was 1.8 hours (IQR 4.3). Median duration under dialysis was 2 days (IQR 3.5). Exchange volume of dialysate varied between 6 and 15 mL/kg at the beginning of PD. In 11 patients, this volume was progressively increased to a maximum of 60 mL/kg (minimum: 30 mL; maximum: 120 mL). Continuous veno-venous hemodiafiltration was required in 3 patients, mainly due to mechanical catheter dysfunction. Complications related to PD occurred in 5 patients: 1 patient developed peritonitis, 1 patient had mechanical catheter dysfunction and 3 patients had peri-catheter leak. Complete recovery of renal function was achieved in 14 patients. Longer time on PD was associated with lower weight before surgery (p = 0.04), longer time on mechanical ventilation and inotropic support (p < 0.001), and longer stay at the ICU (p < 0.001). Time on inotropic support could predict time on PD using a multiple regression model (adjusted R2 = 59%, p = 0.003), adjusted to cardiopulmonary bypass time, time on mechanical ventilation support and weight before surgery (adjusted ß = 0.7, p = 0.005). Eight patients died during hospitalization, due to multiorgan failure (38%), cardiogenic shock (38%), disseminated intravascular coagulation (13%) and septic shock (13%). Longer cardiopulmonary bypass time was associated with in-hospital mortality (149 ± 53 vs 235 ± 46, p = 0.004). Both the time between AKI diagnosis and PD initiation and the time on PD were not associated with in-hospital mortality. Conclusion Our study suggests that PD is a safe and effective dialysis modality in the management of post-cardiac surgery AKI in pediatric population. Early identification of high-risk infants is important to implement preventive measures.

Background Atrial septal defects (ASD) often go unrecognized until very late in life. The impact of ASD closure on life expectancy in elderly patients remains unclear. This study compares the survival of patients≥65-years who underwent ASD closure with their average life expectancy (ALE). Methods Single-centre retrospective study including all patients ≥65-years who underwent ostium secundum (OS) ASD closure (surgical/percutaneous) between 1998-2020. Baseline characteristics and the predicted peri-procedural ALE (as determined per pre-defined national ALE tables) for every given patient were assessed. Results 706 patients underwent OS ASD closure, 37 (5%) had ≥65 years–mean age 69±5 years, 62% presented with heart failure. Mean ASD size=21±9mm, 22% patients had severe tricuspid regurgitation, mean systolic pulmonary artery pressure (SPAP)=50±11mmHg. Five patients were treated surgically. At a mean follow-up of 9±5 years, mortality rate was 46%, occurring 8.8±5.3 years after the procedure. 25 (68%) outlived their predicted ALE. Overall, the mean age of death did not differ from the predicted ALE (79±6 vs. 84±1 years, p=0.304), however there was a 10-year absolute difference between patients who died prematurely vs. those who surpassed ALE (77±4 vs. 87±3 years, p<0.001). Patients who failed to reach ALE had higher SPAP (58±10 vs. 46±8mmHg, p=0.001) and a higher incidence of severe tricuspid regurgitation (42 vs. 12%, p=0.040). Conclusion Survival after late ASD closure was comparable to the expected ALE, though one-third of the patients died prematurely. Higher SPAP and severe tricuspid regurgitation were associated with premature death. ASD closure in elderly requires a thorough evaluation to ensure maximum benefit.

(1) Background: The contribution of gene-specific variants for congenital heart disease, one of the most common congenital disabilities, is still far from our complete understanding. Here, we applied a disease model using human-induced pluripotent stem cells (hiPSCs) to evaluate the function of DAND5 on human cardiomyocyte (CM) differentiation and proliferation. (2) Methods: Taking advantage of our DAND5 patient-derived iPSC line, we used CRISPR-Cas9 gene-editing to generate a set of isogenic hiPSCs (DAND5-corrected and DAND5 full-mutant). The hiPSCs were differentiated into CMs, and RT-qPCR and immunofluorescence profiled the expression of cardiac markers. Cardiomyocyte proliferation was analysed by flow cytometry. Furthermore, we used a multi-electrode array (MEA) to study the functional electrophysiology of DAND5 hiPSC-CMs. (3) Results: The results indicated that hiPSC-CM proliferation is affected by DAND5 levels. Cardiomyocytes derived from a DAND5 full-mutant hiPSC line are more proliferative when compared with gene-corrected hiPSC-CMs. Moreover, parallel cardiac differentiations showed a differential cardiac gene expression profile, with upregulated cardiac progenitor markers in DAND5-KO hiPSC-CMs. Microelectrode array (MEA) measurements demonstrated that DAND5-KO hiPSC-CMs showed prolonged field potential duration and increased spontaneous beating rates. In addition, conduction velocity is reduced in the monolayers of hiPSC-CMs with full-mutant genotype. (4) Conclusions: The absence of DAND5 sustains the proliferation of hiPSC-CMs, which alters their electrophysiological maturation properties. These results using DAND5 hiPSC-CMs consolidate the findings of the in vitro and in vivo mouse models, now in a translational perspective. Altogether, the data will help elucidate the molecular mechanism underlying this human heart disease and potentiates new therapies for treating adult CHD.

Aortic coarctation (AoCo) leads to long-term sequelae that may impair heart function. Data regarding new echocardiographic function parameters such as atrial strain, in affected patients, are scarce. This study aims to describe these parameters in AoCo patients and define their association with severity measures. 53 AoCo patients and 31 healthy controls, aged 12–40 years, were evaluated. Effectively corrected AoCo (cAoCo) was defined as aortic trans-isthmic corrected Doppler gradient (Dgrad) ≤ 20 mmHg ( n = 36), and recoarctation (rAoCo) as Dgrad > 20 mmHg ( n = 17). Dependent variables were: E/E’; atrial reservoir strain (Ares); and atrial conduit strain (Acd). T-tests/Mann–Whitney U tests were used to compare these among groups. Multivariable regression was used to test correlation with systolic blood pressure (SBP), indexed LV mass (ILVM), Dgrad, and the ratio between the narrowest diameter of aortic arch and aorta at diaphragm level (Aoratio). In cAoCo and rAoCo patients, E/E’ was higher ( p < 0.001), Ares, and Acd were lower ( p < 0.001 for both) comparing with controls. Acd was higher in cAoCo than rAoCo ( p = 0.045). Higher Ares was associated with higher Aoratio ( p = 0.002), and lower Acd with higher Dgrad (0.014). EF and GLS were not different among groups. Young patients with effectively corrected aortic coarctation have persistent changes in diastolic function parameters (E/E’ and atrial strain), and these are affected by anatomical sequelae. These patients’ physiology is closer to patients with recoarctation, than to healthy individuals. This provides rationale for a stronger prevention, and treatment, of arterial dysfunction and high left ventricular afterload in these patients.

A 24-year-old man with a history of recent ischaemic stroke was diagnosed with patent foramen ovale (PFO) and referred for closure at our hospital. At admission, besides low peripheral oxygen saturation (88%), physical examination was otherwise normal. We performed intraprocedural transoesophageal echocardiogram that revealed no PFO, although agitated saline injection demonstrated bubbles lately on the left atrium. The atrial septum could not be crossed. We suspected an extracardiac shunt, so pulmonary angiograms were performed that revealed the presence of a left pulmonary arteriovenous malformation (PAVM). A Konar-MF Occluder was used to occlude the PAVM, with a satisfactory result. At 6 months follow-up, the patient had normal peripheral oxygen saturation and a new pulmonary angiogram showed no residual shunt. Intrapulmonary shunts are a rare and under-recognised cause of paradoxical emboli in young patients; physicians should be aware of this diagnosis as percutaneous occlusion is indicated and critical to avoid recurrent ischaemic episodes.

Congenital long QT syndrome (LQTS) is a genetically autosomal heterogeneous disorder of the ion channels and causes about 10% of sudden death infant syndrome in newborns. Its estimated prevalence is approximately 1 in 2500, probably underestimated because of its clinical heterogenicity. Few cases of neonatal LQTS have been reported. In 4% of them, life-threatening arrhythmic events can be the first manifestation of LQTS. The authors report two cases of neonatal LQTS with heterogeneous genetic mutations. Both manifested by bradycardia, one since fetal life. One case had serious arrhythmias during beta blocker therapeutic establishment needing a pacemaker implantation. Genetic mutations found were not the most frequently described in association with neonatal bradycardia, thus the importance of this report. Presentation with bradycardia is relatively frequent in neonatal period, thus LQTS should be actively investigated in neonates with unexplained bradycardia. Beta blocker therapy reduces QTc and avoids arrhythmic events and sudden death.

We report a case of a 28-year-old man lost to follow-up with chronic hypoxaemia and a history of an uncorrected tricuspid hypoplasia, perimembranous ventricular septal defect (VSD) and pulmonary stenosis. Given this initial diagnosis, chronic hypoxaemia was deemed to result from right-to-left shunt through the VSD driven by elevated right ventricle pressures. However, the further investigation identified an inferior sinus venosus atrial septal defect, unveiling the true mechanism behind the clinical scenario. The patient was submitted to surgical correction with clinical improvement. This case illustrates the defiant evaluation of this type of atrial septal defect through echocardiography and underlines the importance of a multimodal evaluation to reach an accurate diagnosis and optimal management.