Isoproterenol Challenge to Detect Arrhythmogenic Right Ventricular Cardiomyopathy

Brief Title

Isoproterenol Challenge to Detect Arrhythmogenic Right Ventricular Cardiomyopathy

Official Title

Utility of Isoproterenol Challenge Test to Detect Disease in Patients With Incomplete Diagnostic Criteria for Arrhythmogenic Right Ventricular Cardiomyopathy

Brief Summary

      This study will examine the usefulness of a new test called an isoproterenol challenge in
      patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and family members who
      may have the disease but do not have clear-cut evidence of it. ARVC is a rare condition that
      runs in families. Heart muscle is replaced with fatty, scar-like tissue, especially in the
      right ventricle (lower pumping chamber of the heart), and can sometimes extend to the left
      ventricle (the main pumping chamber). The fat can interfere with the heartbeat, producing
      abnormal heart rhythms, such as ventricular tachycardia (VT) - a very fast heartbeat that can
      cause sudden death, especially in young people. Isoproterenol is a drug that increases heart
      rate and heart muscle contractions. In isoproterenol challenge, subjects are given increasing
      doses of the drug through a catheter (see details below) to try to produce an abnormal heart
      rhythm.

      ARVC is hard to diagnose with current tests. This study will see if isoproterenol challenge
      provokes VT in patients with the disease and can confirm the diagnosis; if it can detect the
      disease in family members better than currently available tests; and if it provokes abnormal
      rhythms in healthy control subjects. In addition, the study will explore the genetics of ARVC
      and determine whether infection could contribute to its development.

      Patients with ARVC, their family members, and normal volunteers 18 years of age and older may
      be eligible for this study. Candidates are screened with a medical history and physical
      examination, electrocardiogram (EKG), treadmill and bicycle exercise testing, and an
      echocardiogram (ultrasound test of the heart).

      Participants undergo the following tests and procedures:

        -  Blood tests - Blood is collected to study the genetics of ARVC, to test for evidence of
           old infections, and to measure brain natriuretic peptide - a hormone that can increase
           with development of heart failure.

        -  Heart magnetic resonance imaging (MRI). This test looks at heart structure and function.
           MRI uses a magnetic field and radio waves to produce images of body tissues and organs.
           The subject lies on a table that is moved into the scanner (a narrow cylinder), wearing
           earplugs to muffle loud knocking sounds that occur during the scanning process. At some
           time during the test, the subject is given a contrast agent called gadolinium through a
           catheter (thin, flexible tube) in a vein to improve the scan pictures. The scan time
           varies from 30 to 90 minutes, with most scans lasting 60 minutes. (Control subjects do
           not undergo MRI.)

        -  Isoproterenol challenge. Subjects are given increasing doses of isoproterenol through a
           catheter until the heart rate reaches 100 to 120 beats per minute for no more than 1
           hour. A special EKG records heart rhythm during the test and an echocardiogram records
           right and left ventricular function.

        -  QRST surface mapping EKG. This special EKG, done with 64 or 120 leads, maps
           abnormalities of heart rhythm and cardiac conduction during the isoproterenol challenge.
           These tests are like a regular EKG, except that more leads are placed on the chest, and
           on the back as well.

      Patients and family members who wish to have follow-up visits may return to the NIH Clinical
      Center once a year for 5 years for guidance about therapy based on clinical considerations
      and new information or investigations.
    

Detailed Description

      Arrhythmogenic right ventricular cardiomyopathy (ARVC) formerly referred to as arrhythmogenic
      right ventricular dysplasia (ARVD) is a familial hetergenous clinical and molecular disease
      characterized by dilatation and dysfunction of the right ventricle and ventricular
      arrhythmias. The ventricular arrhythmias are heart rate and catecholamine dependent. Not
      infrequently, there is involvement of the left ventricle. The diagnosis of ARVC is critical
      as therapy including implantable defibrillators may prevent sudden death. However,
      identification of affected family members remains a major challenge due to limitation of
      current imaging and diagnostic techniques. We propose (1) to establish the sensitivity and
      specificity of the isoproterenol challenge test for ARVC by testing both patients with known
      ARVC and healthy volunteers; (2) to estimate the proportion of family members who present
      with incomplete criteria for ARVC but are subsequently diagnosed with the condition by an
      isoproterenol challenge test; and, (3) to study the inheritance of ARVC and the potential
      role of occult infection in its development.
    


Study Type

Observational




Condition

Arrhythmic Right Ventricular Cardiomyopathy



Publications

* 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

160

Start Date

May 2004

Completion Date

December 2005


Eligibility Criteria

        INCLUSION CRITERIA:

        Patients with ARVC:

        Either gender, aged greater than 5 years.

        The presence of two major criteria; one major and two minor criteria; or four minor
        criteria from separate diagnostic categories.

        Normal Volunteers:

        Age and gender matched with ARVC patients, age greater than 18 years.

        No known cardiac disease.

        Normal EKG, normal echocardiogram, normal Bruce protocol treadmill exercise test.

        Family Members of Patients with ARVC:

        Either gender, aged greater than 5 years.

        A proband with ARVC

        EXCLUSION CRITERIA:

        Patients with ARVC:

        Pregnancy or lactation excludes tests with potential risk, e.g. radiation, isoprenaline,
        MRI, but does not exclude 12-lead ECG and echocardiogram.

        Coronary artery disease.

        Known infiltrate or congenital heart disease that could mimic the appearances of ARVC.

        Asthma prevents participation in Isoproterenol infusion.

        Any other condition that would prevent participation in the study.

        Normal Volunteers:

        Pregnancy or lactation.

        Asthma.

        Coronary artery disease, hypertension, diabetes, hypertrophic cardiomyopathy, or other
        known cardiomyopathy.

        Known infiltrative or congenital heart disease that could mimic the appearances of ARVC.

        Any Acute or chronic illness.

        Chronic drug therapy.

        Family Members of Patients with ARVC:

        Pregnancy or lactation excludes tests with potential risk, e.g. radiation, isoprenaline,
        MRI, but does not exclude 12-lead ECG and echocardiogram.

        Coronary artery disease.

        Known infiltrative or congenital heart disease that could mimic the appearances of ARVC.

        Asthma prevents participation in Isoproterenol infusion.

        Any other condition that would prevent participation in the study.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

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Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00083395

Organization ID

040194

Secondary IDs

04-CC-0194


Study Sponsor

National Institutes of Health Clinical Center (CC)


Study Sponsor

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Verification Date

December 2005