Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating Founder Variant Carriers.

Background: founder variants cause hypertrophic cardiomyopathy leading to heart failure and malignant ventricular arrhythmias. Exercise is typically regarded as a risk factor for disease expression although evidence is conflicting. Stratifying by type of exercise may discriminate low- from high-risk activities in these patients.

Artificial Intelligence Advancements in Cardiomyopathies: Implications for Diagnosis and Management of Arrhythmogenic Cardiomyopathy.

Purpose Of Review: This review aims to explore the emerging potential of artificial intelligence (AI) in refining risk prediction, clinical diagnosis, and treatment stratification for cardiomyopathies, with a specific emphasis on arrhythmogenic cardiomyopathy (ACM).

Recent Findings: Recent developments highlight the capacity of AI to construct sophisticated models that accurately distinguish affected from non-affected cardiomyopathy patients. These AI-driven approaches not only offer precision in risk prediction and diagnostics but also enable early identification of individuals at high risk of developing cardiomyopathy, even before symptoms occur.

Long-term prognosis of patients with an SCN5A loss-of-function variant and progressive cardiac conduction disorder or Brugada syndrome.

Background: The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown.

Objective: This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events.

Methods: Probands and family members with (likely) pathogenic SCN5A loss-of-function variants were retrospectively included.

Diversity of heart failure phenotypes in transthyretin amyloid cardiomyopathy. More than just heart failure with preserved ejection fraction.

Introduction: Current guidelines recommend suspecting transthyretin amyloid cardiomyopathy (ATTR-CM) in patients over 65 years of age with unexplained left ventricular (LV) hypertrophy in a non-dilated LV, heart failure (HF) and preserved ejection fraction (HFpEF), hypertrophic cardiomyopathy or severe aortic stenosis. However, there is evidence indicating a high prevalence of ATTR-CM in other HF phenotypes. As such, this study aimed to characterize the diversity of HF phenotypes of ATTR-CM by examining the LV ejection fraction and LV dilatation using echocardiography.

Biallelic variants in cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy.

encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of in mice results in sinus pauses and bradycardia and morpholino knockdown of zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy.

Diagnostic value of late gadolinium enhancement at cardiovascular magnetic resonance to distinguish arrhythmogenic right ventricular cardiomyopathy from differentials.

Background: While late gadolinium enhancement (LGE) is proposed as a diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC), the potential of LGE to distinguish ARVC from differentials remains unknown. We aimed to assess the diagnostic value of LGE for ARVC diagnosis.

Methods: We included 132 subjects (60% male, 47 ± 11 years) who had undergone cardiac magnetic resonance imaging with LGE assessment for ARVC or ARVC differentials.

Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients.

Background: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in . The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease.

Methods: Individuals with vEDS throughout the Netherlands were included.

Long-term reliability of the phospholamban (PLN) p.(Arg14del) risk model in predicting major ventricular arrhythmia: a landmark study.

Aims: Recently, a genetic variant-specific prediction model for phospholamban (PLN) p.(Arg14del)-positive individuals was developed to predict individual major ventricular arrhythmia (VA) risk to support decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. This model predicts major VA risk from baseline data, but iterative evaluation of major VA risk may be warranted considering that the risk factors for major VA are progressive.

ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy.

Background: Phospholamban (PLN) p.(Arg14del) variant carriers are at risk for development of malignant ventricular arrhythmia (MVA). Accurate risk stratification allows timely implantation of intracardiac defibrillators and is currently performed with a multimodality prediction model.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

Background And Aims: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.

Methods: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America.

Variants Can Associate with Non-Syndromic Congenital Heart Disease without Aortopathy.

Background: Congenital heart diseases (CHD) are the most common congenital malformations in newborns and remain the leading cause of mortality among infants under one year old. Molecular diagnosis is crucial to evaluate the recurrence risk and to address future prenatal diagnosis. Here, we describe two families with various forms of inherited non-syndromic CHD and the genetic work-up and resultant findings.

Generation and characterization of novel human induced pluripotent stem cell (iPSC) lines originating from five asymptomatic individuals carrying the PLN-R14del pathogenic variant and a non-carrier relative.

The rare genetic alteration PLN-c.(40_42delAGA), leading to the deletion of arginine 14 (p.R14del) in phospholamban, is associated with dilated and arrhythmogenic cardiomyopathies occurring in early-adulthood.

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.

Background: Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.

Methods: We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM.