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.

A polymorphism associated with increased levels of YKL-40 and the risk of early onset of lone atrial fibrillation.

Background: Plasma levels of YKL-40 are elevated in patients with atrial fibrillation (AF). We hypothesized that a single nucleotide polymorphism (SNP) that affects YKL-40 plasma levels is associated to the risk of lone AF.

Findings: We included 178 young patients with lone AF and the first episode before the age of 40 years, and a control group of 875 healthy individuals.

Association of rs2200733 at 4q25 with early onset of lone atrial fibrillation in young patients.

Objective: Genome wide association studies have shown an association between rs2200733 at 4q25 and atrial fibrillation (AF). In this case-control study we investigate the association of rs2200733 and lone AF in young patients.

Methods: We included 196 young patients with lone AF and the first episode before the age of 40 years.

[Clinical and genetic findings in arrhythmogenic right ventricular cardiomyopathy].

Arrhythmogenic right ventricular cardiomyopathy is an inherited disease of the cardiomyocyte. The disease is diagnosed as a syndrome based on criteria that include ventricular arrhythmias, electrocardiographic findings, imaging, tissue characteristics and family history. An implantable cardioverter-defibrillator is generally recommended.

Inflammatory single nucleotide polymorphisms and the risk of atrial fibrillation: a case control study.

Introduction: Systemic inflammation is associated with atrial fibrillation (AF) and inflammatory processes are involved in the pathophysiology of AF. We hypothesized that genetic polymorphisms, which determine the rate of inflammatory cytokines, are associated with increased risk of AF.

Materials And Methods: We included 158 patients with AF and 188 healthy controls.

Familial aggregation of atrial fibrillation: a study in Danish twins.

Background: Heritability may play a role in nonfamilial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared with a dizygotic (DZ) twin in the same situation.

Methods And Results: A sample of 1137 same-sex twin pairs (356 MZ and 781 DZ pairs) in which one or both members were diagnosed with AF were identified in The Danish Twin Registry.

High-efficiency multiplex capillary electrophoresis single strand conformation polymorphism (multi-CE-SSCP) mutation screening of SCN5A: a rapid genetic approach to cardiac arrhythmia.

Mutations in the SCN5A gene coding for the alpha-subunit of the cardiac Na(+) ion channel cause long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, sick sinus node syndrome, progressive conduction disease, dilated cardiomyopathy and atrial standstill. These diseases exhibit variable expressivity, and identification of gene carriers is clinically important, particularly in sudden infant and adult death syndromes. The SCN5A gene comprises 28 exons distributed over 100 kbp of genomic sequence at chromosome 3p21.

Noradrenaline-induced increases in calcium and tension in skeletal muscle conductance and resistance arteries from rats with post-infarction heart failure.

We tested the hypothesis that arterial reactivity to noradrenaline is augmented in congestive heart failure (CHF), which could contribute to the deleterious changes in peripheral vascular resistance and compliance in this condition. From male Wistar rats with post-infarction CHF and sham-operated rats, skeletal muscle conductance and resistance arteries (mean lumen diameters: 514 and 186 microm) were isolated and mounted on wire myographs, and wall tension was recorded in response to cumulative application of acetylcholine and noradrenaline to the vessel segments. In a subset of experiments, wall tension and cytosolic free calcium ion concentration [Ca(2+)](i) were recorded simultaneously during noradrenaline application, using wire myography and the FURA-2 technique.

Ca(2+) sensitisation of force production by noradrenaline in femoral conductance and resistance arteries from rats with postinfarction congestive heart failure.

In this study we tested the hypothesis that arterial myofilament Ca(2+) sensitivity and/or the Ca(2+) sensitising effect of noradrenaline (NA) is enhanced in post-infarction congestive heart failure (CHF), which could contribute to the high peripheral vascular resistance in this condition. Femoral skeletal muscle resistance and conductance arteries (mean lumen diameters of 159 and 519 microm) from rats with CHF and sham-operated control rats were used. Isometric tension development and intracellular free calcium concentration ([Ca(2+)](i)) were measured simultaneously in isolated vessel segments using wire myography and the FURA-2 fluorescence technique.

Prevalence of hyperglycaemia and undiagnosed diabetes mellitus in patients with acute myocardial infarction.

The prevalence of hyperglycaemia and undiagnosed diabetes mellitus was assessed in 214 consecutive patients admitted to the coronary care units with acute myocardial infarction (AMI). On admission, 16 patients (7.5%) had known diabetes, and 19 patients, not previously known to be diabetic, had blood glucose concentrations of greater than or equal to 9 mmol/l.