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UCSD finds genetic time bomb in heart that leads to heart failure in some patients

Each year, thousands of children undergo corrective surgery for congenital heart malformations that improve the immediate function of the heart. However, surgical correction of certain forms of congenital heart disease may not fix the underlying molecular trigger that drives progressive heart failure and sudden death later in life, according to new research from the University of California, San Diego (UCSD) School of Medicine. Over time, a genetic time bomb that causes structural abnormalities at birth, continues to degrade vital heart systems, eventually disrupting the electrical impulses that control the heartbeat.

Now, researchers have determined where and how this progressive heart failure occurs in patients with familial forms of congenital heart disease called atrial septal defects, even after the malformation is surgically corrected. The researchers believe that their findings could, potentially, apply to other forms of congenital heart disease, as well.

In a study published in the April 30 edition of the journal Cell, the investigators used mouse and human subjects to determine that genetic defects in a gene called Nkx2-5, which is critical for embryonic heart formation, continue to exert their detrimental effects over time by degrading the electrical wiring of the heart, in particular, the heart's atrioventricular (AV) node (which normally conducts electrical impulses between the upper and lower chambers of the heart), and by encouraging excessive overgrowth of heart tissue.

According to the March of Dimes, congenital heart defects, which are structural problems present at birth, are the most common birth defect in newborns. Atrial septal defects are sometimes called holes in the heart. A defect between the heart's two upper chambers (the atria) occurs in the septum, the wall that separates the heart's left and right sides. The most common treatment has been s
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
29-Apr-2004


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