Identifying Predictors for Heart Failure Outcomes in Phospholamban p.(Arg14del)-Positive Individuals.

Background: Phospholamban (PLN) p.(Arg14del)-positive individuals are at high risk of developing PLN p.(Arg14del)-related cardiomyopathy, which can lead to progressive heart failure that is poorly amenable to standard heart failure treatment.

Risk factors associated with ventricular fibrillation during first ST-elevation myocardial infarction: Individual participant data analysis of 3 prospective case-control studies.

Background: Most of sudden cardiac death in the adult population is caused by ventricular fibrillation (VF) in the setting of acute myocardial ischemia. The assessment of risk factors for VF in this setting may point to novel causal pathways or new targets for intervention and risk prediction of sudden cardiac death.

Objective: This study aimed to evaluate the effect of family history of sudden death (SD), history of atrial fibrillation (AF), and anterior infarct location on the electrocardiogram on the development of VF during the first ST-elevation myocardial infarction (STEMI).

Personalized sudden cardiac death risk prediction in genetic heart diseases: Beyond one-size-fits-all.

Sudden cardiac death (SCD) risk prediction in genetic heart diseases is essential to identify patients who will benefit from implantable cardioverter-defibrillator (ICD) implantation. Although many prediction tools have been developed, risk prediction remains challenging due to variability in underlying arrhythmic substrates and statistical modeling approaches. This review addresses 2 major challenges in current clinical practice.

Pain after subcutaneous implantable cardioverter-defibrillator implantation: A secondary analysis of the PRAETORIAN-DFT trial.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) overcomes transvenous lead-related complications. Its extrathoracic design results in a generator twice the size of transvenous ICDs.

Objective: We investigated pain after S-ICD implantation and explore predictors for severe pain.

Inherited arrhythmia syndromes - Cardiogenetics.

The inherited arrhythmia syndromes long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are rare cardiac channelopathies associated with a higher risk for malignant arrhythmias and sudden cardiac death. Adequate and timely clinical management of patients remains a challenge and is often based on expert opinions and (small) cohort studies. Particularly, identification of high-risk patients continues to be difficult due to limitations in diagnostic tools and risk prediction models.

Extreme phenotypes of the female athlete's heart: a sports-specific cardiac magnetic resonance imaging study.

Aims: Differentiating physiological exercise-induced cardiac remodelling (EICR) from pathology is challenging, especially in female athletes, where studies using state-of-the-art imaging techniques are lacking. We aimed to investigate extreme phenotypes of EICR in female elite athletes using magnetic resonance imaging (MRI).

Methods And Results: Cross-sectional, multicentre study in female elite athletes using contrast-enhanced cardiac MRI.

Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy.

POPDC2 encodes the Popeye domain-containing protein 2, which has an important role in cardiac pacemaking and conduction, due in part to its cyclic AMP (cAMP)-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia, and morpholino-mediated knockdown of popdc2 in zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in POPDC2 in four families with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects, and hypertrophic cardiomyopathy.

Sex-specific performance of electrocardiographic criteria for left ventricular hypertrophy in elite athletes.

Background: In athletes, left ventricular hypertrophy (LVH) criteria based on electrocardiograms (ECGs) have been validated almost exclusively in men using echocardiography. Sex-specific cardiac magnetic resonance (CMR) validation is lacking.

Objective: To evaluate ECG-LVH criteria against contrast-enhanced CMR in male and female elite athletes.

Age-related penetrance of phospholamban p.Arg14del cardiomyopathy.

Aims: Previous studies have shown that carriers of the pathogenic p.Arg14del variant in phospholamban (PLN) have an increased risk of mortality, heart failure and malignant ventricular arrhythmias. However, there are sparse data on the penetrance of cardiac features in these mutation carriers, and the optimal starting age and intervals of clinical follow-up remain to be defined.

Cocaine-Induced Sudden Cardiac Death Unravelling a SCN5A-Related Disease.

Cocaine consumption is a significant global problem, with an estimated 20 million users worldwide. Sudden cardiac death is frequently reported in this population, particularly among individuals <40 years of age. The role of underlying inherited heart disorders in these cases remains largely unexplored.

Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. Here, we report results from a large genome-wide association study and multitrait analysis including 5,900 HCM cases, 68,359 controls and 36,083 UK Biobank participants with cardiac magnetic resonance imaging. We identified 70 loci (50 novel) associated with HCM and 62 loci (20 novel) associated with relevant left ventricular traits.

Evaluation of polygenic scores for hypertrophic cardiomyopathy in the general population and across clinical settings.

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality, with pathogenic variants found in about a third of cases. Large-scale genome-wide association studies (GWAS) demonstrate that common genetic variation contributes to HCM risk. Here we derive polygenic scores (PGS) from HCM GWAS and genetically correlated traits and test their performance in the UK Biobank, 100,000 Genomes Project, and clinical cohorts.

International Multicenter Cohort Study on Beta-Blocker-Free Treatment Strategies for Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, potentially life-threatening genetic heart disease. Nonselective beta-blockers (BBs) are highly effective in reducing CPVT-triggered arrhythmic events. However, some patients suffer from unacceptable BB side effects and might require strategies without a BB.

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.

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 electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.