Arrhythmic Right Ventricular Cardiomyopathy Clinical Trial
Official title:
Utility of Isoproterenol Challenge Test to Detect Disease in Patients With Incomplete Diagnostic Criteria for Arrhythmogenic Right Ventricular Cardiomyopathy
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.
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. ;
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