Clinical Trial: Cardiac Function in Patients With Hereditary Hemochromatosis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Characterization of Cardiac Function in Subjects With Hereditary Hemochromatosis Who Are New York Heart Association Functional Class I

Brief Summary:

This study will examine the effect of iron buildup in the hearts of patients with hereditary hemochromatosis (HH), a genetic disease that causes the body to accumulate excess amounts of iron. The excess iron can damage the heart, liver, pancreas, skin, and joints. Generally, early treatment with phlebotomy (periodic removal of a unit of blood), and in some cases chelation (using a drug to remove iron from the body) slows down organ damage in HH patients. This study will try to elucidate the effect of iron buildup in the heart and determine if phlebotomy and chelation help keep the heart healthy.

Patients with HH and healthy volunteers 21 years of age and older may be eligible for this study. (Normal volunteers will provide normal values of heart function that will be used to verify abnormalities detected in HH patients.) Patients must have a gene abnormality of Hfe gene Cys282Try homozygote. They may or may not be receiving treatment for HH and they must have no heart symptoms or serious organ damage due to HH. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), Holter EKG (24-hour EKG monitoring, see description below), and chest x-ray.

Participants will undergo the following tests and procedures over 2 to 5 days:

  • Exercise test: The participant exercises on a treadmill while wearing a mouthpiece, which is used to measure how much oxygen is used. Electrodes placed on the chest and arms monitor the heartbeat during the test.
  • Echocardiography: This ultrasound test uses sound waves to take pictures. A small probe is held against the chest to allow a technician to take pictures of the heart and assess its function. A drug called Optison may be inject

    Detailed Summary:

    Hereditary hemochromatosis (HH) is the most common hereditary metabolic abnormality among Caucasians. Homozygosity for the Cys282Tyr mutation, which is the most common known mutation with a predisposition to iron overload, occurs with an estimated frequency of 8 per 1000 in the Caucasians. Hemochromatosis in its advanced stages is associated with severe cardiac complications including congestive heart failure, premature coronary artery disease, and cardiac arrhythmias. The clinical manifestations of HH are due to increased iron absorption and abnormal iron cycling with excessive iron deposition in various organs. Mutations of the Hfe gene on chromosome 6 have been recently identified. Although the pathophysiology remains incompletely understood, a homozygote mutation in Cys282Tyr is present in 84 to 100% of clinically confirmed HH cases. This discovery permits the early diagnosis of this disease and could be used for screening to identify asymptomatic cases. Therefore, the NHLBI in January 2000 launched a 30 million dollar project named HEIRS (HEmochromatosis and IRon overload Study) to screen 1,000,000 adults for HH, and recently completed enrollment.

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    Increased left ventricular wall thickness and mass has been found to be early cardiac manifestations of HH appearing before the onset of contractile dysfunction. Interestingly, a report also indicates that functional abnormalities of the heart can be seen in predominantly asymptomatic HH patient group. Such abnormalities of diastolic function are detected by Doppler echocardiography. Observations support the theory that asymptomatic cardiac dysfunction is detectable with non-invasive cardiac imaging in patients with HH. <TAB>

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    Although the pathophy
    Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

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    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 9, 2003
    Date Started: September 3, 2003
    Date Completion:
    Last Updated: April 20, 2017
    Last Verified: December 23, 2016