Dawood Darbar, M.D.
Study seeks genetic clues to irregular heart rhythm
A defect in the cardiac sodium channel, which is important in regulating the electrical activity of the heart, appears to be responsible for an inherited form of atrial fibrillation (AF).
The finding, reported by Dawood Darbar, M.D., and colleagues in the April 15 issue of Circulation, has implications for the way cardiologists will eventually treat this most common form of irregular heart rhythm by enabling them to tailor medication to the gene defect responsible for it.
While ion channel gene variants have long been associated with AF, the Circulation study is one of the first to show a high incidence of defects in the cardiac sodium channel.
“The cardiac sodium channel plays a key role in cardiac excitability and conduction,” said Darbar, assistant professor of Medicine at Vanderbilt Medical Center.
Defects in this channel have been shown to be associated with a number of inherited arrhythmias of the heart, such as the long QT syndrome, the Brugada syndrome, cardiac conduction disease and sudden cardiac death in patients with normal hearts.
“As the cardiac sodium channel is associated with a number of inherited arrhythmias, we thought it may also play a role in patients who develop AF,” Darbar said.
Darbar and a team of researchers and nurses screened 375 patients with AF who were recruited as part of the Vanderbilt AF registry, which is an ongoing clinical and DNA registry of more than 1,000 patients.
The researchers found that 6 percent of patients with AF had variants in the cardiac sodium channel, much higher than other genes that have been associated with AF. As there are now more than 2 million Americans with AF, this finding might account for 100,000 current cases and half a million cases as the population ages.
“That's why this study is important. It's one of the first to show a high incidence of defects in sodium channel in patients with AF,” Darbar said.
Not only did they find gene variants in 6 percent of their subjects with AF, but when researchers looked at the families of these patients, about 2.7 percent of the variants were novel and had not previously been identified or were known to exist. Furthermore, when the researchers looked at the families of these patients with AF, they found that six of the eight families with novel variants had more than one family member affected by AF, suggesting that in these families the defect in the cardiac sodium channel was responsible for AF.
Darbar said it is important to note that it is only recently that Vanderbilt researchers and others have been able to show that genetics may be important in certain forms of AF, especially the type that occurs in individuals under age 60 who have AF that is not associated with high blood pressure or heart disease — lone AF. However, the genes responsible for the common forms of AF have eluded researchers.
“This study may allow us to one day screen patients with AF, look for defects in the cardiac sodium channel, and if we find one, treatment can be tailored based on the specific defect,” Darbar said.
Other contributors to the Circulation study include Prince Kannankeril, M.D., Brian Donahue, M.D., Ph.D., Gayle Kucera, R.N., Tanya Stubblefield, R.N., Jonathan Haines, Ph.D., Alfred George Jr, M.D., and Dan Roden, M.D.