Unique heart arrhythmia drug represents one of the first molecular-based therapies for heart failure

Heart researchers at Columbia University Medical Center have developed and tested a unique heart arrhythmia drug that could prevent the sudden death of millions of people with heart failure as well as people with an inherited heart disorder. The drug represents one of the first molecular-based therapies for heart failure and avoids the toxicity of current treatments.

Results of the initial animal test, published in the April 9 issue of Science, showed the drug completely prevents sudden death from arrhythmia in mice that have the same heart defect as people with heart failure.

"The drug will be an incredible advance if it works in patients," says Andrew Marks, M.D., chairman of physiology and cellular biophysics, director of the Center for Molecular Cardiology at CUMC, and leader of the new study. "It represents the beginning of an era when drugs will directly fix the molecular defects in heart failure. While our drug is one of the first molecular-based therapies for heart failure and arrhythmias, it won't be the last."

Heart failure is not a heart attack, but a weakening over years of the heart's ability to pump blood. About 50 percent of the 4.6 million patients with heart failure in the United States will die from a type of arrhythmia that produces a fast and erratic beating of the heart. But medications that prevent arrhythmia are so toxic that most have been removed from the market. Other options, defibrillators and heart transplants, are highly invasive and cost hundreds of thousands of dollars.

In the new study, the experimental drug was tested in mice that had the same molecular defect as people with heart failure and some otherwise healthy people who develop fatal arrhythmias during exercise. The defect causes a tiny channel in heart muscle to leak calcium ions into heart cells. The leak can trigger a fatal arrhythmia at any time in heart failure patients or during exercise in people with an inherited defect in the channel.

All 10 mice that received the drug thrived and never developed an arrhythmia, while 8 out of 9 untreated mice became arrhythmic and died. The new drug, developed by Dr. Marks, prevents arrhythmia and sudden death by patching the leak in the heart's calcium channel and is based on Dr. Marks' 15 years of research. Work in Dr. Marks' lab elucidated how the channel works to make the heart beat, and in the past few years, his lab has revealed the channel's connection to heart failure and fatal arrhythmia.

The experimental drug also has great potential in preventing the relentless deterioration of the heart during heart failure, because the leak contributes to the decline. "By fixing the leak, you could potentially slow the progression of heart failure and allow patients to live their lives more normally, not in and out of hospitals," Dr. Marks says. "Our idea is to take a pill instead of spending hundreds of thousands of dollars on implants and heart transplants."