Advertisement

Topics

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

2014-08-27 03:18:28 | BioPortfolio

Summary

The purpose of this trial is to study the genetic and phenotypic aspects of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), and determine the impact of genetic testing in clinical practice.

Description

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC), is an inherited myocardial disease that predominantly affects the right ventricle (RV) and the estimated prevalence in the general population ranges from 1 to 5 in 1000. It is characterized histopathologically by fibro-fatty myocardial replacement and clinically by ventricular arrhythmia that may lead to sudden death, especially in young people and athletes. Clinical diagnosis is based on diagnostic criteria proposed by the International Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (Task Force 1994), but is often difficult due to a broad spectrum of clinical features and a lond period of concealed cardiac expression, with delayed diagnosis.

ARVC/D is familial in 30 to 50% and is typically transmitted as an autosomal dominant trait with variable penetrance. In the past years, the identification of causative mutations in plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2) has fostered the view that ARVC/D is a disorder of the desmosome and provided new insight into its pathogenesis.

The major recent advance in the molecular genetics of ARVD/C might lead to important clinical impact through early and correct diagnosis in patients and relatives, and through potential genotype-phenotype correlations. This key-issue requires first to clarify the optimal molecular strategy, and its efficiency. Such a systematic, detailed and comprehensive mutation screening study is not available until now.

Aim:

Study the genetic and phenotypic aspects of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), and determine the impact of genetic testing in clinical practice.

Methods:

The study was approved by the Pitié-Salpétriêre Hospital ethical committee (CPPRB) and written informed consent was obtained from all participating individuals, recruited in France.

A cohort of 100 unrelated patients with ARVD/C will be recruited. Clinical evaluation will include clinical history, family history, blood sample for DNA analysis 12-lead ECG, signal-average ECG, 24-hour ambulatory ECG, transthoracic echocardiography, MRI and/or radionuclide scintigraphy, and contrast angiography when possible. A clinical diagnosis of ARVD/C is made according to the established European Society of Cardiology / International Society and Federation of Cardiology Task Force major and minor criteria (Task Force 1994).

All available relatives will be proposed for enrollment in the study with blood sample for DNA analysis and non invasive cardiac examination, including 12-lead ECG, signal-average ECG, and transthoracic echocardiography.

Mutational analysis of the five genes encoding desmosomal genes will be performed in all index cases (in plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, desmocollin-2). When mutations will be identified, available relatives will be analysed. In index cases without desmosomal mutation, additional analyses will be performed according to a candidate gene strategy and, when possible, through a genome wide approach and linkage analyses.

Expected results:

Determine the genetic origin in patients with ARVD/C whatever the familial context.

Determine a molecular strategy for routine genetic testing. Determine the impact of genetic testing as a diagnostic test in patients and relatives.

Determine the impact of genetics as a prognostic tool, through phenotype-genotype analyses.

Determine the natural evolution of the disease in relatives, and the penetrance.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Conditions

Cardiomyopathy

Location

Pitié-Salpêtrière Hospital
Paris
France
75013

Status

Recruiting

Source

Assistance Publique - Hôpitaux de Paris

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:18:28-0400

Clinical Trials [199 Associated Clinical Trials listed on BioPortfolio]

Cardiomyopathy Arrhythmia Risk Evaluation

This study will evaluate the prognostic utility of novel ECG markers of electrical instability in patients with cardiomyopathy.

A Study of Anemia in Children With Dilated Cardiomyopathy

Dilated cardiomyopathy is a heart muscle disorder characterized by systolic dysfunction and dilation of the left or both ventricles.Dilated cardiomyopathy can develop in people of any age ...

Hypertrophic Cardiomyopathy Pilot Study

This study evaluates mechanisms of arrhythmogenicity in hypertrophic cardiomyopathy, in comparison to patients with well-understood arrhythmogenic substrate (ischemic cardiomyopathy), as w...

Peripartum Cardiomyopathy

Peri-partum cardiomyopathy is a heart muscle weakness that occurs during or following pregnancy. Research suggests that many initial heart injuries including viruses, pregnancy and other ...

TAKO-TSUBO Cardiomyopathy and Genetic

This is a case-control association study with multicentric prospective recruitment. Tako-TSUBO cardiomyopathy is a new clinical entity mimicking an acute coronary syndrome. It is characte...

PubMed Articles [441 Associated PubMed Articles listed on BioPortfolio]

The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertroph...

Ventricular arrhythmias and sudden cardiac arrest in Takotsubo cardiomyopathy: Incidence, predictive factors and clinical implications.

Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. Life threatening arrhythmias (LTA) can occur and worsen prognosis.

High validity of cardiomyopathy diagnoses in western Sweden (1989-2009).

Hospital discharges with a diagnosis of cardiomyopathy have more than doubled in Sweden since 1987. We validated the cardiomyopathy diagnoses over this time period to investigate that the increase was...

A Case Report of Recurrent Takotsubo Cardiomyopathy in a Patient during Myasthenia Crisis.

Patients with myasthenia crisis can develop Takotsubo stress cardiomyopathy (SC) due to emotional or physical stress and high level of circulating catecholamines. We report a patient who developed rec...

Cirrhotic cardiomyopathy after transplantation: Neither the transient nor innocent bystander.

Cirrhotic cardiomyopathy in end stage liver disease is currently characterized by blunted contractile systolic response to stress with or without diastolic dysfunction in the absence of known heart di...

Medical and Biotech [MESH] Definitions

A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).

An autosomal dominant inherited form of HYPERTROPHIC CARDIOMYOPATHY. It results from any of more than 50 mutations involving genes encoding contractile proteins such as VENTRICULAR MYOSINS; cardiac TROPONIN T; ALPHA-TROPOMYOSIN.

A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).

Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.

An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)

More From BioPortfolio on "Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Cardiology
Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Trial