USC cardiologists have helped lead the charge in bringing a new, more effective therapy to patients suffering from life-threatening heart failure.

Physicians have found that administering nesiritide, a synthesized form of a chemical naturally present in the body, improves short-term symptoms in seriously ill patients with decompensated heart failure, said Uri Elkayam, professor of medicine and director of the Heart Failure Program at USC.

"Over these three years, we have been a major player in the investigation of nesiritide," Elkayam said. USC was one of 40 centers participating in the drug study, and accounted for 15 percent of all patients enrolled.

In a patient with heart failure, the heart cannot pump blood efficiently enough to meet the needs of the body's other organs. That could happen because of coronary artery disease, high blood pressure, weakness of the heart muscle (cardiomyopathy) or other factors. Decompensated heart failure occurs, explained Elkayam, when a heart failure patient is too overloaded with fluids in the body.

"Decompensated heart failure accounts for approximately one million admissions to hospitals in the United States every year," Elkayam said. These patients typically feel very out of breath, cannot lie flat in bed, have a hard time exercising and experience swelling (edema) in the legs or ankles-to the point of going to the hospital.

Once a patient gets to the hospital, doctors administer medication intravenously to help alleviate the symptoms as soon as possible. Cardiologists at LAC+USC Medical Center and USC University Hospital administered nesiritide to patients in a randomized trial, and found it was superior to nitroglycerine and dobutamine-both in effectiveness and in reduced side effects, Elkayam said. (Results were published in the July 27, 2000 issue of the New England Journal of Medicine.)

Physicians in the study measured the pressure within each patient's lungs and heart, he explained. High pressure contributes to shortness of breath.

The researchers found that nesiritide reduced the pressure faster and more significantly within the first three hours of administering the medication than the comparison drug-results presented at November's American Heart Association scientific meeting.

They also have compared it to dobutamine, a commonly administered but problematic drug for patients with decompensated heart failure. "Dobutamine is often associated with increased heart rate and even serious arrhythmias, but nesiritide was associated with signficantly fewer arrhythmias," Elkayam said. "It does not have the same potential for risk as dobutamine."

Further, the patient mortality rate six months after receiving nesiritide for decompensated heart failure was lower than the rate for patients six months after receiving dobutamine, Elkayam reported to physicians at the annual scientific meeting of the Heart Failure Society of America in September.

Elkayam explained that nesiritide is a unique compound-an analog of a brain natriuretic peptide naturally produced in the body.

In a healthy person, the heart's myocardium (or muscular wall) produces brain natriuretic peptide as a way to regulate blood volume. When the heart senses too much blood volume, it responds by secreting this hormone-which gives the brain and kidneys the go-ahead to flush fluid out of the body through urine, and relaxes blood vessel walls. That effectively reduces blood volume.

In patients with heart failure, though, certain receptors that are supposed to pass along information from the brain natriuretic peptide are not very responsive to it, Elkayam said. The signal to flush fluid out of the body gets lost.

But when doctors administer nesiritide, it floods receptors with brain natriuretic peptide. The increased amount of brain natriuretic peptide compensates for the less responsive receptors, and the signal to flush fluid out of the body successfully passes to the brain, kidneys and blood vessels.

"Not only does it cause vasodilation, reducing the work of the heart and pressure in the lungs, but it increases the function of the kidneys so they can produce more urine to get the fluid out," Elkayam said.

While it is not a cure for heart failure, it appears to relieve symptoms quicker and helps patients leave the hospital sooner.

The Food and Drug Administration is still investigating the drug, "but there is a very good chance this drug will be available before the end of the year," Elkayam said. "And we definitely have made it possible to happen."

The drug, known by the trade name Natrecor, is made by Scios Inc.