Multidisciplinary Study of Right Ventricular Dysplasia
The purpose of this study is to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias.
Arrhythmogenic Right Ventricular Dysplasia
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Multidisciplinary Study of Right Ventricular Dysplasia|
- Identifying the cardiac, clinical, and genetic aspects of ARVD [ Time Frame: Measured during the course of the study ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||September 2001|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
ARVD is an uncommon disorder but is considered a major cause of sudden death and life-threatening arrhythmia, in particular in the young population. The prevalence of ARVD is unknown but is certainly underestimated because of the difficulties in obtaining a correct diagnosis. It appears to be particularly frequent in certain geographical areas, probably for a founder effect, such as in northeast Italy, where a large number of ARVD cases and families have been described. A noncontrolled study of the University of Padua reported a frequency of familial forms of about 30 percent, indicating the existence of a defective gene in a large proportion of cases. In the United States the frequency of the disease is unknown, but the number of cases seems to be increasing.
The etiology of ARVD was unknown until very recently. The main hypothesis involved apoptotic mechanisms and, in some cases, a viral infection. However, in the last couple of years, two genes causing ARVD have been identified. The first one encodes plakoglobin, a protein of the cardiac junctions with adhesive and signaling functions. The second ARVD gene is the cardiac ryanodine receptor (RYR2), which has been characterized only very recently by Dr. Danieli's group. In fact, this discovery is so recent that in this study, RYR2 is still considered a potential candidate. The discovery of the first disease genes provides the basis for a candidate gene approach following the hypothesis of a "final common pathway." Thus, major candidates become genes involved in cell-cell adhesion and encoding ion channels.
This is a multidisciplinary, multicenter, collaborative study investigating the cardiac, clinical, and genetic aspects of ARVD. The specific aims are (1) to establish a North American ARVD Registry enrolling ARVD patients and their family members, based on standardized diagnostic test criteria, in a prospective longitudinal follow-up study; (2) to determine the genetic background of ARVD by identifying chromosomal loci and specific gene mutations associated with this disorder; (3) to determine the influence of the genotype on the clinical course of patients with ARVD and explore phenotype-genotype associations that will contribute to improved diagnosis, risk stratification, and therapy; and (4) to develop quantitative methods to assess right ventricular function in order to enhance the specificity and sensitivity of ARVD diagnosis.
|United States, Arizona|
|University of Arizona|
|Tucson, Arizona, United States, 85724|
|Principal Investigator:||Frank I. Marcus, MD||University of Arizona|
|Principal Investigator:||Jeffrey Towbin||Baylor College of Medicine|
|Principal Investigator:||Wojciech Zareba||University of Rochester|