A Titin Missense Variant Causes Atrial Fibrillation.

Rare and common genetic variants contribute to the risk of atrial fibrillation (AF). Although ion channels were among the first AF candidate genes identified, rare loss-of-function variants in structural genes such as have also been implicated in AF pathogenesis partly by the development of an atrial myopathy, but the underlying mechanisms are poorly understood. While truncating variants (tvs) have been causally linked to arrhythmia and cardiomyopathy syndromes, the role of missense variants (mvs) remains unclear.

Clinical Genetic Testing for Atrial Fibrillation: Are We There Yet?

Important progress has been made toward unravelling the complex genetics underlying atrial fibrillation (AF). Initial studies were aimed to identify monogenic causes; however, it has become increasingly clear that the most common predisposing genetic substrate for AF is polygenic. Despite intensive investigations, there is robust evidence for rare variants for only a limited number of genes and cases.

Mutant ANP induces mitochondrial and ion channel remodeling in a human iPSC-derived atrial fibrillation model.

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can model heritable arrhythmias to personalize therapies for individual patients. Although atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and mortality, current platforms to generate iPSC-atrial (a) CMs are inadequate for modeling AF. We applied a combinatorial engineering approach, which integrated multiple physiological cues, including metabolic conditioning and electrical stimulation, to generate mature iPSC-aCMs.

Common genetic variants associated with obesity in an African-American and Hispanic/Latino population.

Introduction: Over 35% of all adults in the world are currently obese and risk of obesity in racial or ethnic minority groups exist in the US, but the causes of these differences are not all known. As obesity is a leading cause of cardiovascular disease, an improved understanding of risk factors across racial and ethnic groups may improve outcomes.

Objective: The objective of this study was to determine if susceptibility to obesity is associated with genetic variation in candidate single nucleotide polymorphisms (SNPs) in African Americans and Hispanic/Latinos.

Association of Rare Genetic Variants and Early-Onset Atrial Fibrillation in Ethnic Minority Individuals.

Importance: Although rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic variation also contributes to the cause of AF in those of minority ethnicity.

Objectives: To assess the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset AF and determine genotype-phenotype associations.

Design, Setting, And Participants: In this cohort, family-based study, probands of African and Hispanic descent with early-onset AF (defined as AF occurring in individuals aged ≤66 years) prospectively enrolled in a clinical and genetic biorepository underwent sequencing of 60 candidate genes.

Relation of Body Mass Index to Symptom Burden in Patients withAtrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and increased mortality. As body mass index (BMI) is increasingly recognized as an important risk factor for the development of AF, we tested the hypothesis that BMI modulates symptomatic AF burden. Cross-sectional data collected from 1,382 patients in the Vanderbilt AF Registry were analyzed.

Electrophysiologic Characterization of Calcium Handling in Human Induced Pluripotent Stem Cell-Derived Atrial Cardiomyocytes.

Human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes (CMs) hold great promise for elucidating underlying cellular mechanisms that cause atrial fibrillation (AF). In order to use atrial-like hiPSC-CMs for arrhythmia modeling, it is essential to better understand the molecular and electrophysiological phenotype of these cells. We performed comprehensive molecular, transcriptomic, and electrophysiologic analyses of retinoic acid (RA)-guided hiPSC atrial-like CMs and demonstrate that RA results in differential expression of genes involved in calcium ion homeostasis that directly interact with an RA receptor, chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TFII).

Genetic modulation of atrial fibrillation risk in a Hispanic/Latino cohort.

Atrial fibrillation (AF) is the most prevalent cardiac rhythm disorder worldwide but the underlying genetic and molecular mechanisms and the response to therapies is not fully understood. Despite a greater burden of AF risk factors in Hispanics/Latinos the prevalence of AF remains low. Over the last decade, genome-wide association studies have identified numerous AF susceptibility loci in mostly whites of European descent.

Use of Capsule Small Bowel Transit Time to Determine the Optimal Enteroscopy Approach.

Background: Capsule small bowel transit time (SBTT) is used to select the most effective enteroscopy approach when targeting capsule endoscopy (CE) findings. Aim of this study was to determine if capsule SBTT can be used to guide the choice of enteroscopy technique for reaching CE abnormalities.

Methods: Single center, retrospective study involving 60 patients.