Ferran Roses-Noguer

Background: Cardiac magnetic resonance (CMR) enables the quantitative characterization of myocardial tissue through parametric myocardial tissue mapping. It shows a strong correlation with invasive histologic techniques in assessing diffuse myocardial fibrosis using native T1 mapping and extracellular volume (ECV), as well as in assessing myocardial edema with T2 mapping. Pediatric applicability is currently limited by a lack of specific reference values for this population, with no recommendations available from the Society of Cardiac Magnetic Resonance. Objective: To determine reference values for global left ventricular native T1, T2 mapping, and extracellular volume fraction and to assess the influence of age, heart rate, body surface area, and sex on these parameters in children and adolescents. Materials and methods: Data were retrospectively collected between 2018 and 2024. A total of 194 healthy children aged up to 17 years underwent CMR. The participants had a mean age of 12.6 (3.4) CI [12.1; 13.1] years (range 0.3–17), and 41% were female. A 1.5-T Siemens MAGNETOM Avanto Fit scanner was used. Native T1 mapping was performed at the base, mid-chamber, and apex of the left ventricle in the short-axis view at end-diastole using a MOLLI sequence, before and 15 min after the administration of a gadobutrol-based contrast agent. T2 mapping was performed before contrast administration at the base, mid-chamber, and apex of the left ventricle at end-diastole using a dark blood turbo spin echo sequence featuring a T2 preparation pulse and a balanced steady-state free precession (bSSFP). Linear regression models were employed to explore the relationships between native T1, ECV, and T2 mapping values and heart rate, age, and body surface area (BSA). Results: The results showed a mean global native T1 of 1004±37 ms, ECV of 25.9±3.6%, and T2 of 48.8±4 ms. T1 and ECV values were negatively correlated with age and BSA ( P P P P =0.953 in the septum and P =0.445 in the free wall). Native T1 values were significantly higher in female patients than in males when analyzed separately for the interventricular septum and the left ventricular free wall ( P =0.014 and P =0.001). Conclusion: This study provides a median range of values in native T1, T2 mapping, and ECV in a pediatric population. The low number of participants under the age of 6 should be taken into account in the results of our study. Our findings corroborate that native T1 is influenced by both age and heart rate, while T2 is primarily affected by age alone. We observed higher native T1 values in females, highlighting the need for separate, sex-specific reference ranges. Therefore, age, heart rate, and sex should be considered in pediatric myocardial mapping.

Background and Aims: Congenital long QT syndrome (LQTS) is a heterogeneous disorder in which genotype and QTc duration modulate the risk of major arrhythmic events (MAEs), but contemporary paediatric outcome data remain limited. This study aimed to characterize clinical features, management strategies, and predictors of MAEs in a nationwide paediatric LQTS cohort. Methods: This retrospective multicentre study analysed children (<18 years) diagnosed with LQTS across 30 tertiary centres (2004–24) using 2022 European Society of Cardiology criteria. MAEs were defined as sudden cardiac death, aborted cardiac arrest, or appropriate implantable cardioverter-defibrillator (ICD) therapy. Results: The cohort included 371 children (58% male; median diagnosis age 6.0 years; interquartile range .25–11 years). Pathogenic/likely pathogenic variants were identified in 86.5%, mainly in KCNQ1, KCNH2, or SCN5A, while 5.7% harboured high-risk genotypes (Jervell–Lange-Nielsen, calmodulinopathies, CACNA1C/Timothy). Beta-blockers were prescribed in 92.4%. Over a median 6-year follow-up, 14 children (3.8%) experienced MAEs, which occurred predominantly in those with high-risk genotypes, QTc ≥550 ms or very early presentation. MAEs were rare in LQT1–3 with QTc 80% arrhythmia-free survival without major complications. Conclusions: In this nationwide paediatric LQTS cohort, MAEs were uncommon and clustered in children with malignant genotypes, markedly prolonged QTc and very early presentation, particularly foetal or neonatal bradycardia. These data support the current genotype and QTc-guided management strategy, with beta-blockers as the cornerstone therapy and selective use of left cardiac sympathetic denervation and ICDs in high-risk profiles.

Aims: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are effective in patients who require protection from sudden cardiac death while avoiding the long-term risks associated with transvenous leads. However, data on their real-world performance in paediatric and young patients remain limited. This study aims to evaluate the safety and efficacy of S-ICDs in a large, multicentre cohort of paediatric and young patients across Europe, with a focus on contemporary implantation practices and clinical outcomes. Methods and results: This is an international, multicentre, observational, retrospective registry on S-ICD outcome in paediatric and young adult patients with congenital heart defects (CHD), cardiomyopathies, channelopathies, and idiopathic ventricular fibrillation (IVF). Data were collected on implantation techniques, acute and long-term outcomes, including defibrillation efficacy, inappropriate (IAS) and appropriate shocks, and complications. Follow-up data were analysed to assess device performance and safety. A total of 223 patients (mean age: 15 ± 3 years; 59% male, 53% cardiomyopathies, 18% channelopathies, 15% IVF, 14% CHD) were included. Most patients underwent implantation using an intermuscular (65%) and two-incision technique (88%). Acute defibrillation success was 100%, and no intraoperative complications occurred. The median follow-up was 28 (IQR: 12–55) months. Appropriate shocks were delivered in 41 (18%) patients (26% rate at 5 years). The first shock was effective in 92% of discrete episodes. The IAS and the complication rates were 20% and 5% at 5 years. Older age, intermuscular pocket, and two-incision technique were associated with fewer complications. Conclusion: This multicentre S-ICD European registry in paediatric and young patients demonstrated favourable outcomes, low IAS, and complication rates.

Introduction: Parvovirus B19 (PVB19) myocarditis is a life-threatening condition with high morbidity and mortality in children. While electrocardiograms are commonly used in the early assessment of myocarditis, no specific electrocardiogram pattern has been consistently linked to PVB19. The objective of this study is to identify a distinctive electrocardiogram pattern associated with PVB19 myocarditis and evaluate its diagnostic accuracy. Methods: This retrospective case–control study included 77 paediatric patients diagnosed with acute myocarditis at a single centre in Barcelona over 16 years (August 2008–September 2024). Twenty patients had PVB19 myocarditis, confirmed by polymerase chain reaction in blood or endomyocardial biopsy, while 57 patients had myocarditis caused by other viruses. Electrocardiogram were assessed by three cardiologists blinded to the aetiological diagnosis. Results: A specific electrocardiogram pattern in the limb leads, characterised by peaked P waves, low QRS complex voltages, and altered repolarisation (manifesting as negative or flat T waves, with or without QTc prolongation), was observed in 14 of 20 patients (70%) with PVB19 myocarditis. Two additional patients exhibited low voltages and altered repolarisation without peaked P waves, and all demonstrated repolarisation abnormalities. In contrast, only 1 of 57 patients with myocarditis from other viruses exhibited the full electrocardiogram pattern. The pattern demonstrated a specificity of 98% and a sensitivity of 70% for PVB19 myocarditis. Conclusion: The identified electrocardiogram pattern shows strong diagnostic specificity for PVB19 myocarditis in paediatric patients and may serve as a useful early diagnostic tool. Further multicentre studies are needed to confirm these findings and explore their clinical implications.

Aims: Landiolol, an ultra-fast acting super-selective beta-blocker, was investigated for the first time in Europe in a prospective clinical study for the management of supraventricular tachycardia (SVT) among paediatric patients. Methods and results: The LANDI-PED study was a prospective, multicentre, open-label, uncontrolled phase III study aiming to investigate the efficacy, safety, and pharmacokinetics (PK) of landiolol in paediatric patients. Sixty patients in surgical and non-surgical settings aged ≥1 day to <18 years with SVTs of various aetiologies received landiolol as a continuous intravenous infusion starting with 5 μg/kg/min titrated up to 40 μg/kg/min depending on heart rate (HR) reduction for up to a maximum of 24 h. The primary endpoint was restoration of normal sinus rhythm (NSR) within 210 min of infusion start. The primary endpoint was achieved in 15 (25.0%) patients. A total of 24 (40.0%) patients achieved a HR reduction of at least 20% within 210 min of landiolol infusion. A significant HR reduction was observed within minutes post-infusion, with a mean (±SD) reduction after 210 min of −13.2 (±11.5)% (P < 0.0001) in the overall population. By infusion end, 51.7% of patients achieved HR reduction of at least 20% from baseline and/or NSR conversion. The PK characteristics were consistent with the known profile of landiolol among adults. The most common adverse drug reaction was hypotension (10%). Conclusion: Landiolol is effective and safe in the treatment of SVTs in the paediatric population as demonstrated by reduction of HR and/or restoring NSR. Landiolol was well tolerated with no novel safety concerns reported. Clinical Trial Registration: EU Clinical Trial Register; EudraCT Number: 2015-001129-17.

This study aimed to report the findings of cardiac magnetic resonance imaging (CMR) with quantitative mappings in infants presenting with new-onset heart failure, as well as to assess the capabilities of endomyocardial biopsy (EMB) and CMR in detecting inflammatory cardiomyopathies and determining their etiology. In a prospective analysis of infants who underwent CMR with tissue mappings, EMB, and genetic testing, the sample was categorized into two groups: those with inflammatory cardiomyopathy and negative genetics (indicative of possible myocarditis) and those with positive genetics (indicative of possible dilated cardiomyopathy). All patients exhibited similar clinical presentations, echocardiographic dysfunction, and elevated troponins and NT-proBNP levels. Additionally, they all met the diagnostic criteria for inflammatory cardiomyopathy based on EMB findings (≥14 mononuclear cells, ≥7 T-lymphocytes/mm2). EMB results unveiled significant differences in the presence of inflammation and edema between the two groups, with higher troponin levels correlating with increased inflammation. Notably, when focusing on CMR, neither the classic criteria nor the 2018 Lake Louise criteria (LLC) could effectively differentiate between the two groups. Only late gadolinium enhancement (LGE) appeared to be associated with myocarditis in this cohort, while other LLC and tissue mappings did not exhibit a similar correlation. Importantly, there was no observed correlation between the inflammation detected through EMB and CMR. Conclusions: The onset of heart dysfunction in infants can result from either inherited factors or viral infections, both of which may involve inflammation. However, the precise role of EMB and CMR in determining the etiology of such cases remains poorly defined. While CMR demonstrates high sensitivity in detecting inflammation, our experience suggests that it may not effectively differentiate between these two groups. A comprehensive diagnostic approach is essential when addressing this challenge, which includes considering EMB (with attention to the number of T-lymphocytes and the presence of oedema), specific CMR criteria, notably LGE and tissue mappings, as well as the identification of viral agents in cardiac tissue and troponin levels. Additionally, genetic tests should be conducted when evaluating these patients. What is Known: • EMB is the gold standard diagnostic test for myocarditis but it is not universally accepted. • The diagnostic value of the 2018-LLC in pediatric patients is still undefined. What is New: • Both EMB and CMR may show inflammation in infants with new-onset heart failure of any aetiology. • A global approach should be used when facing this diagnostic challenge, including the EMB (number of T-lymphocytes and oedema), some CMR criteria, specially LGE and mappings, the detection of viral agents in cardiac tissue and troponins. Genetic tests should also be performed when studying these patients.

Calmodulinopathy due to mutations in any of the three CALM genes (CALM1–3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5–19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter–defibrillator. Number and percentages of patients with CALM variants and LQTS, CPVT, LQTS/CPVT overlap, IVF, UD, and SCD are reported in the upper left part of the graphical abstract together with two examples of LQTS and CPVT electrocardiograms. In the upper right part, it is shown a graphical representation of the reduction of all cardiac events and SCD between the original cohort (up to 2019) and the cases enrolled between 2019 and 2023. In the lower part, it is reported the number or percentage of CALM patients with cardiomyopathies, congenital heart defects, and neurological features. CALM, calmodulin; LQTS, long QT syndrome; CPVT, catecholaminergic polymorphic ventricular tachycardia; ICD, implantable cardioverter–defibrillator; IVF, idiopathic ventricular fibrillation; UD, uncertain diagnosis; SCD, sudden cardiac death.