Multidisciplinary Study of Right Ventricular Dysplasia

Brief Title

Multidisciplinary Study of Right Ventricular Dysplasia

Official Title

Multidisciplinary Study of Right Ventricular Dysplasia

Brief Summary

      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.

Detailed Description


      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.

Study Type


Primary Outcome

Identifying the cardiac, clinical, and genetic aspects of ARVD


Heart Diseases


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

September 2001

Completion Date

July 2010

Primary Completion Date

July 2010

Eligibility Criteria

        Inclusion Criteria:

          -  Males and females over the age of puberty

          -  Suspected ARVD based on the presence of major or minor Task Force Criteria

        Exclusion Criteria:

          -  Children younger than 12 years of age

          -  Internal cardioverter defibrillator (ICD) in place for more than 2 years (for

          -  Individuals with monomorphic ventricular ectopy of predominantly RBBB morphology

          -  Individuals with obvious cardiomyopathic abnormalities of structure or function
             predominantly affecting the left ventricle

          -  Individuals with other conditions that might be mistaken for right ventricular
             dysplasia such as congenital heart disease, e.g., atrial septal defect, anomalous
             drainage of the pulmonary vessels into the right atrium, and Ebstein's malformation

          -  Individuals unwilling to undergo diagnostic testing at the nearest enrolling center




12 Years - 90 Years

Accepts Healthy Volunteers



Frank I. Marcus, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party

Principal Investigator

Study Sponsor

University of Arizona


 National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

Frank I. Marcus, MD, Principal Investigator, University of Arizona

Verification Date

January 2013