Current guidelines recommend regular screening for first-degree relatives of gene-elusive arrhythmogenic right ventricular cardiomyopathy (ARVC) patients using a similar regimen as for genotype-positive/phenotype-negative relatives. However, the multifactorial nature of gene-elusive ARVC may necessitate a different approach. This study aimed to determine the yield of cardiac screening in first-degree relatives of ARVC probands without a validated genetic cause.

Exercise training improves contractile function and can reduce arrhythmia burden after a myocardial infarction (MI). How exercise modifies the proarrhythmic status is uncertain.

Acoramidis achieves near-complete (≥90%) transthyretin stabilization and is approved to reduce cardiovascular-related hospitalization in transthyretin amyloid cardiomyopathy. Its effects on kidney function are not well characterized.

Aortic enlargement is a powerful predictor of dissection and rupture, yet it is rarely evaluated during routine myocardial perfusion imaging, despite the widespread availability of computed tomography (CT) attenuation correction scans. The aim of this study was to determine whether fully automated, opportunistically derived, artificial intelligence-based aortic measurements from myocardial perfusion imaging CT attenuation correction scans are associated with adverse outcomes in a large multicenter cohort.

Conventional activation mapping of atrial fibrillation (AF) during clinical procedures is limited by low-amplitude, fractionated electrograms and cycle length variability. The Tau20-RETROmapping stimulator-recorder system (TauRhythm Therapies, United Kingdom) is an investigational device used to identify nonpulmonary vein AF drivers by real-time, high-density activation mapping of uniform wavefronts during AF. We validated the accuracy of the system and applied it to left atrial mapping for evidence of AF drivers.

The pathogenesis of Takotsubo syndrome (TTS) is poorly understood, but differences in outcome depending on the triggering factor imply differences in the pathophysiology. Beyond the established trigger-based InterTAK (International Takotsubo Registry) classification, the newly proposed distinction between primary and secondary TTS aims to differentiate emotionally primed heart dysfunction from TTS driven by direct myocardial injury. To explore these potential differences, we utilized cardiovascular magnetic resonance imaging to assess left ventricular function, myocardial edema, and myocardial injury across the InterTAK classification and between primary and secondary TTS.

Virtual panel analysis (VPA) of exome data is a common approach for the molecular diagnosis of congenital heart disease (CHD). However, differences in gene panel composition and patient inclusion criteria limit the evaluation of its diagnostic utility. This study aims to assess the diagnostic yield of VPA in a cohort of patients with CHD across 3 academic centers.

The DES gene encodes the IF (intermediate filament) protein desmin, which connects different multiprotein complexes, such as the cardiac desmosomes, and is highly important for the structural integrity of cardiomyocytes. Pathogenic DES mutations cause filament assembly defects leading to cardiomyopathies. However, most DES variants listed in genetic disease databases are currently classified as variants of unknown significance. Here, we characterized 21 different DES variants of unknown significance and 18 additional proline variants, localized in a highly conserved stretch at the C terminus of the desmin coil-2 subdomain.

Heart failure (HF) remains a pressing health concern, with rising prevalence globally. Subjectivity and ambiguity in the definition of HF and its antecedent stages have limited research, global surveillance, and prevention programs. To address this, several cardiac societies and foundations convened to standardize the definition of HF in 2021 and designated stage B or pre-HF to identify individuals at risk of developing HF. In subsequent years, substantial progress and changes have been made in aspects of preventing HF, improving HF diagnosis and management, and recognizing the importance of the affected individual's voice. Global differences and disparities in HF are better understood, as are causes and comorbidities leading to differences in care, which are also influenced by access to care. This consensus document presents the Second Universal Definition of Heart Failure, aiming to standardize terminology and facilitate a uniform approach for clinicians, researchers, health systems, and policymakers. In this definition, the classification of HF phenotypes moves away from rigid left ventricular ejection fraction cutoffs, instead grouping HF into reduced, preserved, and improved ejection fraction categories to better reflect clinical realities. A universal classification of HF causes is also proposed. The document also addresses the dynamic trajectories of HF-improvement, remission, and recovery-and highlights the impact of social determinants and geographic variation on HF risk and outcomes. By providing a comprehensive, standardized framework for HF definition and classification, this document seeks to improve prevention, early detection, and management of HF worldwide, ultimately enhancing patient care and advancing global cardiovascular health.

Alterations in microtubule dynamics have been shown to affect cardiomyocyte membrane stiffness and modulate ion channels, including the cardiac sodium channel. While conditions, such as heart failure and Duchenne muscular dystrophy, are associated with increased detyrosination of microtubules and reduced sodium current, a potential role for microtubule detyrosination in arrhythmogenic cardiomyopathy has not been explored. We here investigated the impact of microtubule detyrosination on membrane stiffness, cardiac sodium channel distribution, and function in mouse and human models of arrhythmogenic cardiomyopathy.

Undertreatment and delayed treatment of aortic stenosis (AS) are common, both of which are associated with increased mortality. Historically, assessment of quality for AS care has focused on peri- and postprocedural outcomes. The American Heart Association Target: AS registry is the first national registry to provide data and evaluate quality for upstream processes of care for patients with AS.

This study evaluated the ability of the ABC Bicuspid Sizing Algorithm to predict aortic root rupture in patients treated with transcatheter aortic valve replacement using SAPIEN 3 valves.

Spontaneous automaticity of sinoatrial node cells (SANCs) is driven by a system that couples ion channels, membrane clock and Ca2+clock, the sarcoplasmic reticulum generated LCRs (local subsarcolemmal Ca2+releases). Although LCRs are critically dependent on high basal cAMP and both PKA (protein kinase A)- and CaMKII (Ca2+/calmodulin dependent protein kinase II)-dependent protein phosphorylation, the link between cAMP and CaMKII remains unclear. Here, we tested a hypothesis that high cAMP activates EPAC (exchange protein directly activated by cAMP) which increases basal CaMKII activity, reinforcing the Coupled clock pacemaker system, to boost LCRs and accelerate spontaneous SANC firing.

Right ventricular-pulmonary arterial coupling is a known prognostic marker in patients with tricuspid regurgitation (TR). However, its assessment by cardiac magnetic resonance and its clinical implications have not been evaluated. We aimed to assess the prognostic role of a cardiac magnetic resonance surrogate of right ventricular-pulmonary arterial coupling in a large cohort of patients with a spectrum of TR severity.