Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design.

Introduction: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries.

Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy.

Aims: Cardiac myosin light chain kinase (cMLCK) phosphorylates ventricular myosin regulatory light chain 2 (MLC2v) and regulates sarcomere and cardiomyocyte organization. However, few data exist regarding the relationship between cMLCK mutations and MLC2v phosphorylation, particularly in terms of developing familial dilated cardiomyopathy (DCM) in whom cMLCK gene mutations were identified. The purpose of the present study was to investigate functional consequences of cMLCK mutations in DCM patients.

Functional analysis of KCNH2 gene mutations of type 2 long QT syndrome in larval zebrafish using microscopy and electrocardiography.

Heterologous expression systems play a vital role in the characterization of potassium voltage-gated channel subfamily H member 2 (KCNH2) gene mutations, such as E637K which is associated with long QT syndrome type 2 (LQT2). In vivo assays using zebrafish provide a means for testing genetic variants of cardiac disease; however, limited information on the role of the E637K mutation is available from in vivo systems and their utility has yet to be fully exploited in the context of LQT2. We sought to evaluate the ability of the E637K mutant channel to restore normal repolarization in larval zebrafish with a human KCNH2 orthologue, kcnh2a-knockdown.

J Waves for Predicting Cardiac Events in Hypertrophic Cardiomyopathy.

Objectives: This study sought to investigate whether the presence of J waves was associated with cardiac events in patients with hypertrophic cardiomyopathy (HCM).

Background: It has been uncertain whether the presence of J waves predicts life-threatening cardiac events in patients with HCM.

Methods: This study evaluated consecutive 338 patients with HCM (207 men; age 61 ± 17 years of age).

Huge right ventricular mass lesion associated with genital malignant tumor: a case report.

Background: Primary heart tumors are rare, whereas metastatic heart tumors occur more frequently.

Case Presentation: We report a case of a 75-year-old Japanese woman who had metastatic heart tumors of the right ventricle. Although she initially received antibiotic therapy following a diagnosis of pneumonia and pleuritis, her symptoms worsened, and she developed dyspnea and bilateral lower limb edema.

Whole exome sequencing combined with integrated variant annotation prediction identifies a causative myosin essential light chain variant in hypertrophic cardiomyopathy.

Background: The development of candidate gene approaches to enable molecular diagnosis of hypertrophic cardiomyopathy (HCM) has required extensive and prolonged efforts. Whole exome sequencing (WES) technologies have already accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. As a result, there is great interest in extending the use of WES to any of Mendelian diseases.

Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation.

Background: Few rare variants in atrial fibrillation (AF)-associated genes have been functionally characterized to identify a causal relationship between these variants and development of AF. We here sought to determine the clinical effect of rare variants in AF-associated genes in patients with lone AF and characterized these variants electrophysiologically and bioinformatically.

Methods And Results: We screened all coding regions in 12 AF-associated genes in 90 patients with lone AF, with an onset of 47±11 years (66 men; mean age, 56±13 years) by high-resolution melting curve analysis and DNA sequencing.

Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

Introduction: Myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) usually shows a patchy distribution, which may not be detected by pathological Q waves on 12-lead ECGs. Fragmented QRS complexes (fQRS) reflect intraventricular conduction delay and can be a marker of myocardial fibrosis. We assessed whether fQRS show better correlation with myocardial fibrosis than pathological Q waves in HCM.

Right ventricular hypertrophy is associated with cardiovascular events in hypertrophic cardiomyopathy: evidence from study with magnetic resonance imaging.

Background: Although left ventricular (LV) morphology and function have been well studied in hypertrophic cardiomyopathy (HCM), few data exist regarding the right ventricle. Accordingly, we studied right ventricular (RV) morphology and function and their effect on cardiovascular events in HCM using cardiac magnetic resonance (CMR) imaging.

Methods: This retrospective study included 106 HCM patients (age 61.

Increased extent of myocardial fibrosis in genotyped hypertrophic cardiomyopathy with ventricular tachyarrhythmias.

Background: Occurrence of malignant ventricular tachyarrhythmias such as ventricular tachycardia and fibrillation (VT/VF) in hypertrophic cardiomyopathy (HCM) can be related to the extent of myocardial fibrosis. Although late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging has been used to detect myocardial fibrosis, few data exist regarding relationships between CMR-determined myocardial fibrosis and VT/VF in genotyped HCM populations.

Objective: We retrospectively investigated whether the extent of LGE can be increased in HCM patients with VT/VF compared to those without VT/VF in the genotyped HCM population.

Fragmented QRS predicts heart failure progression in patients with hypertrophic cardiomyopathy.

Background: Although fragmented QRS complex (frag-QRS) reflecting intra-ventricular conduction delay has been shown to be a prognostic marker for cardiac events, few data exist regarding the impact of frag-QRS on cardiac events in hypertrophic cardiomyopathy (HCM).

Methods And Results: Ninety-four HCM patients (56 male; mean age, 58 ± 17 years) were retrospectively investigated. Frag-QRS was defined as the presence of various RsR' patterns in at least 2 contiguous ECG leads.

Compound heterozygosity deteriorates phenotypes of hypertrophic cardiomyopathy with founder MYBPC3 mutation: evidence from patients and zebrafish models.

Although most founder mutation carriers of hypertrophic cardiomyopathy (HCM), such as the cardiac myosin-binding protein C gene (MYBPC3), arose from a common ancestor exhibit favorable clinical phenotypes, there still remain small fractions of these carriers associated with increased cardiovascular events. However, few data exist regarding the defining factors that modify phenotypes of these patients, particularly in terms of multiple gene mutations. Therefore, we assessed genotype-phenotype correlations and investigated factors that contribute to phenotypic diversities of mutation carriers from 488 unrelated HCM probands.

High sensitivity of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens in hypertrophic cardiomyopathy.

Background: Myocardial scarring can be assessed by cardiac magnetic resonance imaging with late gadolinium enhancement and by endomyocardial biopsy. However, accuracy of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens remains unknown in hypertrophic cardiomyopathy. We investigated whether late gadolinium enhancement in the whole heart reflects microscopic myocardial scarring in the small biopsied specimens in hypertrophic cardiomyopathy.

Impact of systolic dysfunction in genotyped hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere, and approximately 5% of cases of HCM show systolic dysfunction with poor prognosis. Few data exist regarding the systolic dysfunction in a large population of genotyped HCM subjects.

Hypothesis: The aim of this study was to assess the systolic dysfunction and prognosis in sarcomere gene mutation carriers.

Immediate disappearance of large thrombus in left atrium without evidence of systemic embolization after heparin treatment.

We report an unusual case with giant left atrial thrombus which disappeared soon after starting anticoagulation without evidence of further systemic embolism. A 75-year-old female with non-valvular atrial fibrillation suddenly complained of pain of her right arm and left leg. Contrast-enhanced computed tomography showed occlusion of right brachial and left popliteal arteries.

A KCR1 variant implicated in susceptibility to the long QT syndrome.

The acquired long QT syndrome (aLQTS) is frequently associated with extrinsic and intrinsic risk factors including therapeutic agents that inadvertently inhibit the KCNH2 K(+) channel that underlies the repolarizing I(Kr) current in the heart. Previous reports demonstrated that K(+) channel regulator 1 (KCR1) diminishes KCNH2 drug sensitivity and may protect susceptible patients from developing aLQTS. Here, we describe a novel variant of KCR1 (E33D) isolated from a patient with ventricular fibrillation and significant QT prolongation.