December 1, 2011

Study points to personal treatment for atrial fibrillation

Study points to personal treatment for atrial fibrillation

Vanderbilt Heart & Vascular Institute researchers have identified a genetic variant in patients who respond well to a common form of therapy for atrial fibrillation (AF), a condition that affects more than 2 million Americans.

According to the study, which will be published this month in the Journal of the American College of Cardiology, individuals who carry a particular polymorphism respond better to rate control therapy than those who do not carry this genetic variant.

Dawood Darbar, M.D.

Dawood Darbar, M.D.

“Previous studies have shown that ventricular rate control is an acceptable form of therapy for many patients with AF, but identifying those who are most likely to respond to this treatment has always been a challenge,” said Dawood Darbar, M.D., associate professor of Medicine and director of the Vanderbilt Arrhythmia Service.

AF can be medically managed in one of two ways: prevention of the arrhythmia with anti-arrhythmic drugs or allowing AF to occur, but preventing rapid heart rates. The latter therapy is called ventricular rate control. Studies have clearly shown that rhythm control is no better than rate control in terms of survival, Darbar said.

“It’s important to control the ventricular rate during AF because prolonged rapid ventricular rates during AF significantly increase the risk of developing heart failure.”

Clinical factors such as age, hypertension, coronary artery disease and gender failed to predict response to rate control therapy, so the purpose of this study was to determine whether a common genetic variant would predict which patients would respond better to rate control therapy.

There are two common genetic polymorphisms in the B1-adrenergic receptor that regulate how well one responds to the therapies for AF, which include beta-blockers, calcium channel blockers and digoxin.

“Because beta-blockers mediate their effects through the B1-adrenergic signaling pathway, we thought that perhaps these two common polymorphisms in these receptors might also modulate how well patients respond to rate control for AF,” Darbar said.

The B1-adrenergic receptor polymorphism is carried by about one-third of Caucasians and nearly 40 percent of African-Americans.

“What we found is that individuals who carry this particular polymorphism responded better to ventricular rate control therapy and that they required lower doses of beta-blockers as compared to those who do not carry this genetic variant,” Darbar said.

“To our surprise, we also found there were no clinical predictors to tell you who would or who would not respond to rate control treatment.”

The findings suggest that physicians may need to consider other therapies for AF like anti-arrhythmic drugs or even ablation for patients who don’t carry the polymorphism.

“This is a preliminary study and the results need to be confirmed by other investigators. We are hoping to conduct a randomized controlled trial where patients will undergo genetic testing up front after which they will be randomized to a particular form of therapy based on whether they carry this common genetic variant or not,” Darbar said.

“This study provides us with the data to propose a proper clinical trial with the ultimate goal of tailoring therapies for AF patients based on their genetic make-up.”

This study was made possible, in part, by the existence of the Vanderbilt AF Registry, a genetic and clinical database of more than 2,000 patients whose DNA and clinical response to therapy have been followed by Darbar and colleagues for the past eight years.

“This study emphasizes the importance of personalizing therapy for an individual patient,” Darbar said.

First author of the JACC article is Babar Parvez, M.D., and other contributors include Nagesh Chopra, M.D., Shane Rowan, M.D., Joseph Vaglio, M.D., Raafia Muhammad, M.D., and Dan Roden, M.D., all of Vanderbilt.