The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

Aims: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics.

Methods And Results: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course.

Diastolic Ventricular Interaction in Heart Failure With Preserved Ejection Fraction.

Background Exercise-induced pulmonary hypertension is common in heart failure with preserved ejection fraction ( HF p EF ). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise. Methods and Results Contrast stress echocardiography was performed in 30 HF p EF patients, 17 hypertensive controls, and 17 normotensive controls (healthy).

Update on hypertrophic cardiomyopathy and a guide to the guidelines.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment.

Standing on the Shoulders of Giants: J.A.P. Paré and the Birth of Cardiovascular Genetics.

Sudden death and stroke afflicted a family from rural Quebec with such frequency as to be called the Coaticook curse by the local community. In Montreal in the late 1950s, a team of physicians led by J.A.

Dynamic conduction and repolarisation changes in early arrhythmogenic right ventricular cardiomyopathy versus benign outflow tract ectopy demonstrated by high density mapping & paced surface ECG analysis.

Aims: The concealed phase of arrhythmogenic right ventricular cardiomyopathy (ARVC) may initially manifest electrophysiologically. No studies have examined dynamic conduction/repolarization kinetics to distinguish benign right ventricular outflow tract ectopy (RVOT ectopy) from ARVC's early phase. We investigated dynamic endocardial electrophysiological changes that differentiate early ARVC disease expression from RVOT ectopy.

When rare illuminates common: how cardiocutaneous syndromes transformed our perspective on arrhythmogenic cardiomyopathy.

The classic cardiocutaneous syndromes of Naxos and Carvajal are rare. The myocardial disorder integral to their pathology - arrhythmogenic cardiomyopathy - is arguably not uncommon, with a prevalence of up to 1 in 1,000 despite almost certain under-recognition. Yet the study of cardiocutaneous syndromes has been integral to evolution of the contemporary perspective of arrhythmogenic cardiomyopathy - its clinical course, disease spectrum, genetics, and cellular and molecular mechanisms.

Insights and challenges in hypertrophic cardiomyopathy, 2012.

We present a contemporary overview of hypertrophic cardiomyopathy (HCM), incorporating recent thinking on disease mechanisms and advances in therapy. Clinical, pathological, genetic, and mechanistic definitions of HCM are discussed. The genetic profile of HCM in both adults and children is explored to the extent of present knowledge.

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions.

Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria.

Background: With recognition of disease-causing genes in arrhythmogenic right ventricular cardiomyopathy, mutation analysis is being applied.

Methods And Results: The role of genotyping in familial assessment for arrhythmogenic right ventricular cardiomyopathy was investigated, including the prevalence of mutations in known causal genes, the penetrance and expressivity in genotyped families, and the utility of the 2010 Task Force criteria in clinical diagnosis. Clinical and molecular genetic evaluation was performed in 210 first-degree and 45 second-degree relatives from 100 families.

Genetics of Dilated Cardiomyopathy: Risk of Conduction Defects and Sudden Cardiac Death.

Dilated cardiomyopathy is familial in at least 40--60% of cases and causal mutations have been identified in more than 40 different genes. Mutations in lamin A/C (LMNA) and desmosomal components appear associated with increased risk of sudden cardiac death, the latter in the context of left-dominant arrhythmogenic cardiomyopathy. Specific clinical features may be valuable in identifying patients with these mutations.

Mutational heterogeneity, modifier genes, and environmental influences contribute to phenotypic diversity of arrhythmogenic cardiomyopathy.

Background: Arrhythmogenic cardiomyopathy is one of the leading causes of sudden cardiac death in the < or =35-year age group. The broad phenotypic spectrum encompasses left-dominant and biventricular subtypes, characterized by early left ventricular involvement, as well as the classic right-dominant form, better known as arrhythmogenic right ventricular cardiomyopathy. Mendelian inheritance patterns are accompanied by incomplete penetrance and variable expressivity, the latter manifesting as diversity in morphology, arrhythmic burden, and clinical outcomes.

Genetics of restrictive cardiomyopathy.

Restrictive physiology, a severe form of diastolic dysfunction, is characteristically observed in the setting of constrictive pericarditis and myocardial restriction. The latter is commonly due to systemic diseases, some of which are inherited as mendelian traits (eg, hereditary amyloidosis), while others are multifactorial (eg, sarcoidosis). When restrictive physiology occurs as an early and dominant feature of a primary myocardial disorder, it may be termed restrictive cardiomyopathy.

Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) has a prevalence of at least 1 in 1000, is a leading cause of sudden cardiac death in people aged < or =35 years, and accounts for up to 10% of deaths from undiagnosed cardiac disease in the <65 age group. The classic form of the disease has an early predilection for the right ventricle, but recognition of left-dominant and biventricular subtypes has prompted proposal of the broader term arrhythmogenic cardiomyopathy. The clinical profile of the disease bridges the gap between the cardiomyopathies and inherited arrhythmia syndromes.

Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity.

Objectives: We sought to investigate the clinical-genetic profile of left-dominant arrhythmogenic cardiomyopathy (LDAC).

Background: In the absence of coronary disease and left ventricular (LV) systolic dysfunction, lateral T-wave inversion and arrhythmia of LV origin are often considered benign. Similarly, chest pain with enzyme release might be attributed to viral myocarditis.

Left ventricular noncompaction and cardiomyopathy: cause, contributor, or epiphenomenon?

Purpose Of Review: To discuss unresolved issues pertaining to aetiology and diagnosis of isolated left ventricular noncompaction.

Recent Findings: Left ventricular noncompaction may be sporadic or familial and is linked to mutations in mitochondrial, cytoskeletal, Z-line, and sarcomeric proteins. Severe childhood manifestations include fetal hydrops or sudden infant death syndrome.

The utility of magnetic resonance imaging in the evaluation of arrhythmogenic right ventricular cardiomyopathy.

Purpose Of Review: Perceptions of the utility of cardiovascular magnetic resonance in the evaluation of arrhythmogenic right ventricular cardiomyopathy have changed considerably in the past decade. This review offers an up-to-date perspective on the diagnostic role of cardiovascular magnetic resonance in the genetics era.

Recent Findings: Originally hailed as a putative gold standard in arrhythmogenic cardiomyopathy, cardiovascular magnetic resonance has received a more guarded reception lately owing to interobserver variability and lack of standardized protocols.

Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a recognized cause of sudden cardiac death, which may be prevented by timely detection and intervention. Clinical diagnosis of ARVC is fraught with difficulties in both index cases and relatives owing to the nonspecific nature of associated features, diverse phenotypic manifestations, and a lack of conspicuous abnormalities in the early, "concealed" phase. During the past 7 years, researchers have isolated causative mutations in several components of the desmosome, shedding light on the molecular mechanisms underlying the disease and offering the promise of genetic testing as a diagnostic tool.