Every year, nearly 12 million American heart patients are wired up and put on bikes or treadmills for stress tests, designed to reveal how well blood flows to their heart muscle.
In 75 percent of those tests, doctors inject a radioactive tracer into the bloodstream, and a gamma-ray camera reveals how well the blood flows into the coronary arteries during both rest and exercise.
These "nuclear" stress tests show constricted blood vessels or dark spots - evidence of muscle scarring from past heart attacks. But they are expensive and time-consuming. And they expose the patient's entire body to radiation, for as long as 72 hours - the equivalent of dozens of chest X-rays.
Now, a Massachusetts company called Acusphere Inc. says it has developed an injectable substance - a gas carried in microscopic polymer spheres - that can show blood flow into the heart muscle just as accurately as a nuclear stress test, but faster and without radiation.
The microspheres, as they are called, increase the reflectivity of the blood to ultrasonic sound, Acusphere scientists say. That makes it possible to show "perfusion" - blood flow through the heart muscle - in a standard echocardiogram, a cheaper, quicker and more widely available procedure that probes the heart with sound waves rather than radiation.
"Because of its ability to look at perfusion, it's very exciting," said Dr. Roxy Senior, director of echocardiology and nuclear cardiology at Northwick Park Hospital in London, who participated in clinical studies of the product. "There's a whole new way of looking at a patient now."
The product, still in clinical trials, is called AI-700. Acusphere unveiled its latest clinical results this week at a meeting of the American Society of Echocardiography in Baltimore.
If it works, AI-700 would be a welcome way to improve stress echo tests and salvage many images that just aren't good enough today, said Dr. Theodore P. Abraham, associate director of echocardiography at Johns Hopkins Medicine, who has no connection to Acusphere or its clinical studies.
"One in every four Americans has a potential for blocked coronary arteries," he said. But echocardiograms, even with the tracers now available, can only show movement in the walls of the heart.
With a tracer such as AI-700, "not only can we outline the border of the heart wall muscle, but now we can actually see it as it goes into the wall muscle" via the coronary blood vessels, Abraham said.
Some people, he said - particularly very large patients or smokers with emphysema - would still require nuclear stress tests. That's because sound energy can't always penetrate easily to their hearts. "This is a physical limitation of ultrasound," he said.
Acusphere spokesman Stephen D. Schultz said AI-700 consists of porous spheres a third to a quarter of the size of human red blood cells. Mixed in water and injected into the bloodstream, they are small enough to travel "just about anywhere in the vascular system," he said.
The spheres are made of the same synthetic polymer, called PLGA, used in some dissolving surgical stitches and other drug delivery systems. Acusphere has various forms under development for delivering different drugs.
The spheres in AI-700 have a honeycomb structure, with voids containing perfluorocarbon gas, an inert substance with many medical uses. In an echocardiogram, the gas enhances the reflectivity of the high-frequency sound, revealing the blood flow - or its absence - within the heart muscle.
After about five minutes - "more than sufficient for the sonographers to get the information they need," Schultz said - the AI-700 spheres begin to break down. The perfluorocarbon gas is expelled through the lungs, and the PLGA is broken down by the liver and spleen and eliminated from the body.
Acusphere's product is not the first contrast agent invented to enhance the sonic reflectivity of blood in the heart, Schultz said. But the others are made with natural substances such as albumin and lipids.
While they help reveal heart movement and blood flow, Schultz said, they break down before they can show blood perfusion into the heart muscle, and the FDA has not approved them for that purpose.
AI-700 may have a rival, however. A California company called Point Biomedical Corp. is seeking FDA approval for CARDIOsphere, a synthetic product that Schultz said is similar enough to make the firm a direct competitor.
The first part of the Acusphere's Phase 3 clinical trials, reported at this week's meeting in Baltimore, found that AI-700 was just as accurate as nuclear stress tests at identifying patients with coronary artery disease.
Senior said the nuclear stress test is a valuable diagnostic tool, and less invasive than angiography, which requires the insertion of a catheter and dye directly into the heart.
But it's problematic for reasons that go beyond the patient's exposure to radioactivity. The radioactive tracers must be tightly controlled. Patients and staff must be shielded, and not every hospital can afford to offer the service or make it available 24 hours a day, Senior said. The tests can cost $1,500 to $2,000 each and take five hours to complete.
By contrast, a stress echo test enhanced with AI-700 can be performed in 15 to 30 minutes, on short notice, for as little as half the cost of a nuclear stress test.
"And every hospital has a machine," Senior said. It could be wheeled to the patient's bedside or used in the emergency room
The low cost and high sensitivity could even enable doctors to offer screening to patients with high coronary risk factors but no apparent cardiac symptoms, Senior said.
Acusphere says it's developing microspheres with different structures and porosities, each designed for optimum delivery of various drugs. One could deliver toxic anti-cancer drugs more quickly and with fewer side effects; another could transport drugs that don't dissolve well in the bloodstream.
The company says it also has had success with tests of inhaled microspheres that could deliver an asthma drug directly to the lungs, in a once-a-day sustained release form not now available.
AI-700 would be the company's first product to reach the market. Senior said the results of Phase 3 clinical trials should be published at the end of this year. Application to the Food and Drug Administration for new drug approval would follow early next year. With approval, AI-700 could reach the market in 2008.