Prevalence of deleterious cardiomyopathy variants in early-onset atrial fibrillation.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke, heart failure, and death. Recent studies suggests that individuals with early onset of AF could be at increased risk of developing heart failure and dilated cardiomyopathy. This study aimed to identifying genetic variants in a broad panel of cardiomyopathy genes among early-onset AF individuals.

Rare and Common Genetic Variation Underlying Atrial Fibrillation Risk.

Importance: Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution of rare variants to disease risk warrants characterization in large cohorts.

Objective: To identify rare predicted loss-of-function (pLOF) variants associated with AF and elucidate their role in risk of AF, cardiomyopathy (CM), and heart failure (HF) in combination with a polygenic risk score (PRS).

Atrial fibrillation: age at diagnosis, incident cardiovascular events, and mortality.

Background And Aims: Patients with atrial fibrillation (AF) are at increased risks of cardiovascular diseases and mortality, but risks according to age at diagnosis have not been reported. This study investigated age-specific risks of outcomes among patients with AF and the background population.

Methods: This nationwide population-based cohort study included patients with AF and controls without outcomes by the application of exposure density matching on the basis of sex, year of birth, and index date.

Loss of Cardiac Splicing Regulator Is Associated With Early-Onset Atrial Fibrillation.

We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of , we demonstrated altered splicing of sarcomere genes (, , , and ), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function.

Polygenic risk score for ACE-inhibitor-associated cough based on the discovery of new genetic loci.

Aims: To search for sequence variants associated with ACEi discontinuation and to test their association with ACEi-associated adverse drug reactions (ADRs).

Methods And Results: A genome-wide association study (GWAS) on ACEi discontinuation was conducted, including 33 959 ACEi-discontinuers and 44 041 controls. Cases were defined as persons who switched from an ACEi treatment to an angiotensin receptor blocker.

Genome-wide association study identifies 18 novel loci associated with left atrial volume and function.

Aims: Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA volume and function using cardiac magnetic resonance imaging data.

Methods And Results: We used the UK Biobank, which is a large prospective population study with available phenotypic and genetic data.

Atrial fibrillation-a complex polygenetic disease.

Atrial fibrillation (AF) is the most common type of arrhythmia. Epidemiological studies have documented a substantial genetic component. More than 160 genes have been associated with AF during the last decades.

Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes.

Introduction: Current clinical guidelines for management of diabetic peripheral neuropathy (DPN) emphasize good glycemic control. However, this has limited effect on prevention of DPN in type 2 diabetic (T2D) patients. This study investigates the effect of insulin treatment on development of DPN in a rat model of T2D to assess the underlying causes leading to DPN.

Cardiac magnetic resonance systematically overestimates mitral regurgitations by the indirect method.

Objective: Cardiac MRI is quickly emerging as the gold standard for assessment of mitral regurgitation, most commonly with the indirect method subtracting forward flow in aorta from volumetric segmentation of the left ventricle. We aimed to investigate how aortic flow measurements with increasing distance from the aortic valve affect calculated mitral regurgitations and whether measurements were influenced by breath-hold regimen.

Methods: Free-breathing and breath-hold phase contrast flows were measured in aorta at valve level, sinotubular (ST) junction, mid-ascending aorta and in the pulmonary trunk.

Early-onset atrial fibrillation patients show reduced left ventricular ejection fraction and increased atrial fibrosis.

Atrial fibrillation (AF) has traditionally been considered an electrical heart disease. However, genetic studies have revealed that the structural architecture of the heart also play a significant role. We evaluated the functional and structural consequences of harboring a titin-truncating variant (TTNtv) in AF patients, using cardiac magnetic resonance (CMR).

Loss-of-Function Variants in Cytoskeletal Genes Are Associated with Early-Onset Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with an increased risk of heart failure, stroke, dementia, and death. Recently, titin-truncating variants (TTNtv), which are predominantly associated with dilated cardiomyopathy (DCM), were associated with early-onset AF. Furthermore, genome-wide association studies (GWAS) associated AF with other structural genes.

Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse.

Aims: Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse.

Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation.

A family history of atrial fibrillation constitutes a substantial risk of developing the disease, however, the pathogenesis of this complex disease is poorly understood. We perform whole-exome sequencing on 24 families with at least three family members diagnosed with atrial fibrillation (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10).