Reactivation of the Epicardium at the Origin of Myocardial Fibro-Fatty Infiltration During the Atrial Cardiomyopathy.

Rationale: Fibro-fatty infiltration of subepicardial layers of the atrial wall has been shown to contribute to the substrate of atrial fibrillation.

Objective: Here, we examined if the epicardium that contains multipotent cells is involved in this remodeling process.

Methods And Results: One hundred nine human surgical right atrial specimens were evaluated.

Association of Serum Cholesterol Efflux Capacity With Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

Background: Serum cholesterol efflux capacity, a biomarker that integrates contributors and modulators of the initial step of the reverse cholesterol transport, has been associated with atherosclerosis independently of high-density lipoprotein (HDL) cholesterol level.

Objectives: The authors evaluated the prognostic impact of serum cholesterol efflux capacity on mortality in a large cohort of patients hospitalized for an acute myocardial infarction (MI).

Methods: Serum cholesterol efflux capacity, cholesteryl ester transfer protein (CETP) activity, total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and triglyceride levels were measured in 1,609 consecutive patients admitted with an acute MI.

Differentiation and quantification of fibrosis, fat and fatty fibrosis in human left atrial myocardium using ex vivo MRI.

Background: Atrial fibrillation is associated with an atrial cardiomyopathy composed mainly of fibrosis and adipose tissue accumulation. We hypothesized that MRI, when used in an optimal ex vivo setting allowing high spatial resolution without motion artifacts, can help characterizing the complex 3D left atrial (LA) wall composition in human myocardial samples, as compared to histology.

Methods: This prospective case-control study was approved by the institutional review board.

Cardiac MR Strain: A Noninvasive Biomarker of Fibrofatty Remodeling of the Left Atrial Myocardium.

Purpose To determine whether left atrial (LA) strain quantification with cardiac magnetic resonance (MR) imaging feature tracking is associated with the severity of LA fibrofatty myocardial remodeling at histologic analysis. Materials and Methods This prospective case-control study was approved by the institutional review board. LA strain was evaluated with cardiac MR feature tracking between January 2014 and March 2015 in 13 consecutive patients (mean age, 61 years ± 19; nine male) with mitral regurgitation in the 24 hours before mitral valve surgery and 13 age- and sex-matched healthy control subjects.

The genetics underlying acquired long QT syndrome: impact for genetic screening.

Aims: Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors.

Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction.

Transmission distortion of disease-causing alleles in long QT syndrome (LQTS) has been reported, suggesting a potential role of KCNQ1 and KCNH2 in reproduction. This study sought to investigate parental transmission in LQTS families according to ethnicity, gene loci (LQT1-3: KCNQ1, KCNH2, and SCN5A) or severity of channel dysfunction. We studied 3782 genotyped members from 679 European and Japanese LQTS families (2748 carriers).

Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study.

Aims: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration.

Methods And Results: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN, CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%).

Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QT syndrome.

Background: Long-QT syndrome (LQTS) is characterized by such striking clinical heterogeneity that, even among family members carrying the same mutation, clinical outcome can range between sudden death and no symptoms. We investigated the role of genetic variants as modifiers of risk for cardiac events in patients with LQTS.

Methods And Results: In a matched case-control study including 112 patient duos with LQTS from France, Italy, and Japan, 25 polymorphisms were genotyped based on either their association with QTc duration in healthy populations or on their role in adrenergic responses.

Novel SCN5A mutations in two families with "Brugada-like" ST elevation in the inferior leads and conduction disturbances.

Aims: Brugada syndrome (BrS) is an inherited cardiac disease characterized by ST segment elevation in V1-V3 ECG leads. Mutations SCN5A gene encoding for the cardiac voltage-gated Na(+) channel are found in some BrS patients, but also in family members with isolated conduction disturbances. However, some patients show coved ST elevation in the inferior or lateral leads whose association with SCN5A and familial conduction disturbances are poorly known.

MOG1: a new susceptibility gene for Brugada syndrome.

Background: Brugada syndrome (BrS) is caused mainly by mutations in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Na(v)1.5. However, ≈ 20% of probands have SCN5A mutations, suggesting the implication of other genes.

R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation.

Background: Loss-of-function mutations in the gene KCNQ1 encoding the Kv7.1 K(+) channel cause long QT syndrome type 1 (LQT1), whereas gain-of-function mutations are associated with short QT syndrome as well as familial atrial fibrillation (FAF). However, KCNQ1 mutation pleiotropy, which is capable of expressing both LQT1 and FAF, has not been demonstrated for a discrete KCNQ1 mutation.

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Background: Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype.

Objective: This study sought to perform a retrospective analysis of BrS databases from 9 centers that have each genotyped >100 unrelated cases of suspected BrS.

Female predominance and transmission distortion in the long-QT syndrome.

Background: Congenital long-QT syndrome is a disorder resulting in ventricular arrhythmias and sudden death. The most common forms of the long-QT syndrome, types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and KCNH2, respectively. Although inheritance of the long-QT syndrome is autosomal dominant, female predominance has often been observed and has been attributed to an increased susceptibility to cardiac arrhythmias in women.

Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population.

The QT interval (QT) reflects cardiac ventricular repolarization and varies according to various known factors such as heart rate, gender and age. Nevertheless, a high intrasubject stability of the QT-RR pattern also suggests that a genetic component contributes to individual QT length. To determine whether single nucleotide polymorphisms (SNPs) in genes encoding cardiac ion channels were associated with the heart-rate corrected QT (QTc) length, we analyzed two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2,008 healthy subjects.

Heart rate influences on repolarization duration and morphology in symptomatic versus asymptomatic KCNQ1 mutation carriers.

QT and Tp/Te intervals were longer in patients with LQT1 (n = 67) than in nonaffected subjects (n = 52) but did not differentiate symptomatic (n = 21) from asymptomatic patients (n = 46). At fast heart rate, the time to accumulate the last part of total T-wave area (the t50-97 interval) was longer in symptomatic carriers compared with asymptomatic patients (119 +/- 19 vs 106 +/- 15 ms, p <0.01).

New KCNQ1 mutations leading to haploinsufficiency in a general population; Defective trafficking of a KvLQT1 mutant.

Objective: KCNQ1 mutations lead to the long QT syndrome (LQTS), characterized by a prolonged QT interval, syncopes and sudden death. However, some mutations are associated with non-penetrant phenotype (no symptoms, QTc normal or borderline). The objective of this study was to determine whether KCNQ1 variants are associated with borderline QTc prolongation in a general population and to evaluate the frequency of carriers.

Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations.

Objectives: We hypothesized that neonatal long QT syndrome (LQTS) with 2:1 atrioventricular block (AVB) could be related to HERG mutations.

Background: Early onset of LQTS is rare but carries a high risk of life-threatening events such as ventricular arrhythmias and conduction disorders. There are no data on possible gene specificity.