Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design.

Background: Despite advances in ablation and other therapies for AF, progression of atrial fibrillation (AF) remains a significant clinical problem, associated with worse prognosis and worse treatment outcomes. Upstream therapies targeting inflammatory or antifibrotic mechanisms have been disappointing in preventing AF progression, but more recently genetic and genomic studies in AF suggest novel cellular and metabolic stress targets, supporting prior studies of lifestyle and risk factor modification (LRFM) for AF. However, while obesity is a significant risk factor, weight loss and risk factor modification have not been successfully applied in a US population with AF.

Transcriptomic Insights into the Atrial Fibrillation Susceptibility Locus near the and Genes.

Genome-wide association studies have identified a locus on chromosome 10q22, where many co-inherited single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF). This study seeks to identify the impact of this locus on gene expression at the transcript isoform level in human left atria and to gain insight into potential causal variants. Bulk RNA sequencing was analyzed to identify myozenin 1 () and synaptopodin 2-like () transcript isoforms and the association of common SNPs in this region with transcript isoform expression levels.

Impact of Contact Force on Pulsed Field Ablation Outcomes Using Focal Point Catheter.

Background: Conventional focal radiofrequency catheters may be modified to enable multiple energy modalities (radiofrequency or pulsed field [PF]) with the benefit of contact force (CF) feedback, providing greater flexibility in the treatment of arrhythmias. Information on the impact of CF on lesion formation in PF ablations remains limited.

Methods: An in vivo study was performed with 8 swine using an investigational dual-energy CF focal catheter with local impedance.

Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions.

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression of atrial fibrillation, the potential impact of environmental determinants on this prevalent condition has received comparatively less attention.

The Global Burden of premature cardiovascular disease, 1990-2019.

Aims: Premature cardiovascular disease (pCVD) definition varies in literature, with age cut-offs ranging from 50-65 years. While there is some literature available on pCVD in North America, comprehensive data on its global burden is still lacking which hinders the development of efficient strategies for early detection and prevention. In this study we aimed to investigate the global trends in pCVD related morbidity and mortality from 1990 to 2019.

Novel functional atrial fibrillation risk genes and pathways identified from coexpression analyses in human left atria.

Background: Genomewide association studies have associated >100 genetic loci with atrial fibrillation (AF), but establishing causal genes contributing to AF remains challenging.

Objective: The purpose of this study was to determine candidate novel causal genes and mechanistic pathways associated with AF risk loci by incorporating gene expression and coexpression analyses and to provide a resource for functional studies and targeting of AF-associated genes.

Methods: Cis-expression quantitative trait loci were identified for candidate genes near AF risk variants in human left atrial tissues.

Predictors of successful same-day discharge and 1-year outcomes after left atrial appendage closure.

Background: Same-day discharge (SDD) following left atrial appendage closure (LAAC) is increasingly common but predictors of successful SDD and 1-year clinical outcomes have not been described.

Objective: The purpose of this study was to explore predictors of successful SDD and report 1-year outcomes in patients undergoing LAAC with SDD.

Methods: A prospective analysis was performed over a 20-month period of 225 consecutive patients that underwent LAAC in a large, academic hospital.

Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage.

Atrial fibrillation (AF) is strongly associated with risk of stroke and heart failure. AF promotes atrial remodeling that increases risk of stroke due to left atrial thrombogenesis, and increases energy demand to support high rate electrical activity and muscle contraction. While many transcriptomic studies have assessed AF-related changes in mRNA abundance, fewer studies have assessed proteomic changes.

Cardiac Pressure Overload Decreases ETV1 Expression in the Left Atrium, Contributing to Atrial Electrical and Structural Remodeling.

Background: Elevated intracardiac pressure attributable to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 (ETS translocation variant 1) signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling.

Proarrhythmic effects from competitive atrial pacing and potential programming solutions.

Background: Programmed long AV delays and intrinsic long first degree AV block may increase risk for competitive atrial pacing (CAP) in devices without CAP avoidance algorithms.

Methods: Patients identified with CAP-induced mode switch episodes were followed clinically from September 2013 to August 2019. Attempts to avoid CAP included shortening of postventricular atrial refractory period (PVARP) or postventricular atrial blanking period (PVAB), or change to AAI or DDI modes.