Novel risk predictor of arrhythmias for patients with potassium channel related congenital Long-QT Syndrome.

Background: Congenital long-QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.

Objective: We aimed to evaluate the potential utility of exercise stress test (EST) electrocardiographic markers in identifying high-risk LQTS patients.

Cardiomyocyte and stromal cell cross-talk influences the pathogenesis of arrhythmogenic cardiomyopathy: a multi-level analysis uncovers DLK1-NOTCH pathway role in fibro-adipose remodelling.

Arrhythmogenic Cardiomyopathy (ACM) is a life-threatening, genetically determined disease primarily caused by mutations in desmosomal genes, such as PKP2. Currently, there is no etiological therapy for ACM due to its complex and not fully elucidated pathogenesis. Various cardiac cell types affected by the genetic mutation, such as cardiomyocytes (CM) and cardiac mesenchymal stromal cells (cMSC), individually contribute to the ACM phenotype, driving functional abnormalities and fibro-fatty substitution, respectively.

Italian Cardiological Guidelines (COCIS) for Competitive Sport Eligibility in athletes with heart disease: update 2024.

Nearly 35 years after its initial publication in 1989, the Italian Society of Sports Cardiology and the Italian Federation of Sports Medicine (FMSI), in collaboration with other leading Italian Cardiological Scientific Associations (ANCE - National Association of Outpatient Cardiology, ANMCO - National Association of Inpatient Cardiology, SIC - Italian Society of Cardiology), proudly present the 2023 version of the Cardiological Guidelines for Competitive Sports Eligibility. This publication is an update of the previous guidelines, offering a comprehensive and detailed guide for the participation of athletes with heart disease in sports. This edition incorporates the latest advances in cardiology and sports medicine, providing current information and recommendations.

Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.

Role of Calmodulin in Cardiac Disease: Insights on Genotype and Phenotype.

Calmodulin, a protein critically important for the regulation of all major cardiac ion channels, is the quintessential cellular calcium sensor and plays a key role in preserving cardiac electrical stability. Its unique importance is highlighted by the presence of 3 genes in 3 different chromosomes encoding for the same protein and by their extreme conservation. Indeed, all 3 calmodulin () genes are among the most constrained genes in the human genome, that is, the observed variants are much less than expected by chance.

Continuous Rhythm Monitoring With Implanted Loop Recorders in Children and Adolescents With Brugada Syndrome.

Background: Young (<18 years of age) patients with Brugada syndrome (BrS) are often under-represented in BrS studies and their management, especially related to syncopal episodes, remains unclear.

Objectives: This study sought to describe the arrhythmia prevalence among young patients with BrS undergoing continuous rhythm monitoring by implantable loop recorder (ILR) and to assess the etiology behind syncope of undetermined origin.

Methods: A total of 147 patients with BrS with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n = 77, 52%) and adolescents (age 13-18 years; n = 70, 48%).

Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients.

Background: Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel-mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2.

The Dynamic Clamp Technique: A Robust Toolkit for Investigating Potassium Channel Function.

The dynamic clamp technique has emerged as a powerful tool in the field of cardiac electrophysiology, enabling researchers to investigate the intricate dynamics of ion currents in cardiac cells. Potassium channels play a critical role in the functioning of cardiac cells and the overall electrical stability of the heart. This chapter provides a comprehensive overview of the methods and applications of dynamic clamp in the study of key potassium currents in cardiac cells.

Candidacy and long-term outcomes of subcutaneous implantable cardioverter-defibrillators in current practice in patients with hypertrophic cardiomyopathy.

Background: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up.

Methods: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study.

Long QT syndrome: importance of reassessing arrhythmic risk after treatment initiation.

Background And Aims: Risk scores are proposed for genetic arrhythmias. Having proposed in 2010 one such score (M-FACT) for the long QT syndrome (LQTS), this study aims to test whether adherence to its suggestions would be appropriate.

Methods: LQT1/2/3 and genotype-negative patients without aborted cardiac arrest (ACA) before diagnosis or cardiac events (CEs) below age 1 were included in the study, focusing on an M-FACT score ≥2 (intermediate/high risk), either at presentation (static) or during follow-up (dynamic), previously associated with 40% risk of implantable cardioverter defibrillator (ICD) shocks within 4 years.

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 is limited data on the outcomes of ICD use in children.

Implantable loop recorders in patients with Brugada syndrome: the BruLoop study.

Background And Aims: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes.

Methods: A total of 370 patients with BrS and ILRs (mean age 43.

Multiplexed Assays of Variant Effect and Automated Patch-clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome (LQTS) is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often owing to lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.