Heart research shifts to early detection

It is one of the most enduring and intractable problems in medicine: In half of men and two-thirds of women who die abruptly from heart disease, there is no warning, no symptom of a problem brewing.

Now, scientists from Boston to Tokyo are intensifying a high-stakes race to better understand the phenomenon and come up with a way to detect trouble deep inside the heart. They are using sound and light to peer directly into the heart's vessels, hunting for clumps of fat not much larger than a grain of rice and primed to rupture.

The experimental detection systems are all the talk at major meetings of cardiologists, with preliminary findings presented last month at a conference in Washington and more reports expected next week at a Chicago convention.

"It's like a mystery novel -- we're trying to recreate the crime looking backwards in time. You have the smoking gun, which is a heart attack," said Dr. Sergio Waxman, a cardiovascular researcher at Lahey Clinic and leader of a plaque-detection trial. "The question is, how do we prevent this from happening?"

If one of the approaches under development succeeds -- and that's not guaranteed -- the consequences could be profound, for patients and scientists alike. It could translate into tens of thousands of lives saved annually. And it could have equally staggering economic implications, with one market analyst estimating that detection systems have the potential to generate billions of dollars in revenue, dwarfing recent innovations such as stents.

But the efforts to detect dangerous deposits of fat also have reinforced long-standing rifts in one of the most competitive and lucrative realms of medicine.

One camp of cardiovascular specialists argues that heart disease can't be stopped without looking at the patient's entire coronary system. They remain deeply skeptical about the ability of any test to identify the precise location of a potential problem, and even if researchers develop such a test, the doubters ask: What would we do with that information?

"We need to draw a very careful line about raising hopes of the public that there will be some wonderful gizmo that will allow us to put the finger in the dike," said Dr. Peter Libby, chief of cardiovascular medicine at Brigham and Women's Hospital. "We could save tens of thousands of heart attacks if we applied what we already know -- like the current guidelines on cholesterol, blood pressure, diet. But these are things that are boring to the public."

Another camp -- and that's the camp working on the detection systems -- emphasizes the importance of tracking down those fat deposits believed to be most likely to rupture and create fatal blockages. Champions of that approach have a name for those deposits: vulnerable plaque.

"What I generally say is I agree it's a systemic disease, and it is very important to treat it systemically," said Dr. James E. Muller, chief executive of a Burlington biotech company called InfraReDx, which has attracted $50 million from investors to create a plaque-detection system. "But, unfortunately, if you go into a coronary care unit, you'll find it's full of people who've been taking their statins to lower their cholesterol and even taking an aspirin -- the best systemic therapy possible -- and they still have a heart attack."

And when that patient undergoes surgery to open a blockage, Muller said, "you find there's one spot in the artery that caused the clot."

To locate that spot, researchers must travel directly into the heart because sufficiently detailed snapshots can't be taken through skin, bone, and muscle.

There's nothing new about shooting images inside the heart, of course: Specialists do that routinely while clearing blocked vessels during a procedure called angioplasty. But while the picture-taking systems used during those operations are good at spying big blockages, they're not so good when it comes to examining the contents of smaller, rupture-prone plaques, said Dr. Momtaz Wassef of the National Heart, Lung, and Blood Institute.

So researchers have enlisted some tried-and-true technologies, including ultrasound and infrared, to attempt to identify troublesome fat deposits in what Muller described as a "harsh environment" for such testing: the beating human heart. They're not looking for major blockages. Instead, they're hunting for plaques with the right mix of fat and a thin cap on top that make them vulnerable to rupture.

Thousands of patients around the world are participating in studies of these detection systems.

A California company called Volcano, for example, has enrolled 3,000 patients in a trial of its advanced ultrasound system, said Vince Burgess, the company's marketing vice president.

Another technique measuring echoes of light -- optical coherence tomography -- has been tried on about 150 patients at Massachusetts General Hospital by Dr. Ik-Kyung Jang. A Westford company called LightLab is selling the optical systems in Europe, China, and South Korea, and US trials are almost finished, said Joe Schmitt, the firm's chief technology officer.

Muller's InfraReDx has also begun a trial of its system, which uses infrared laser light to read the chemical fingerprints of plaques. The trial ultimately will include about 100 patients at five hospitals, including Lahey in Burlington.

InfraReDx has received preliminary FDA approval to test its method, but that only means it's acceptable to use the technique in human arteries; it says nothing about the system's ability to detect fatty deposits. Muller said the company intends to seek approval for that more-specific use in March, and hopes to begin selling units next summer.

"I take it for granted that one or more of these techniques will work," said Dr. Gary Mintz, director of publications of the Cardiovascular Research Foundation, a private medical research organization. "But they do have some risks. There are complications associated with every technique. So, the question is, is it worth it?"

Use of plaque-detection systems would be limited to patients already undergoing invasive procedures, such as angioplasty. Such patients, who have had a life-threatening heart problem, are at dramatically higher risk of another one, and, developers of the systems argue, could especially benefit from detection of dangerous fat deposits.

The market could be substantial: Muller said 1 million US patients and 2 million worldwide annually undergo procedures to clear clogged arteries.

Jan Wald, a medical device analyst at the financial services firm A.G. Edwards & Sons who is familiar with the competing plaque-detection systems, said that "in the investment community, the question is: How quick are the techniques going to be utilized and available? Is it going to be realized in 2007? 2012? 2020?"

But even if scientists succeed in perfecting a system to pinpoint dangerous fat deposits, there's no agreement on what to do about them. Would it be enough to give patients high doses of cholesterol-lowering drugs? Would it be necessary to implant tiny metal scaffolds to keep arteries open?

"Are you going to put three, four, five stents in people with vulnerable plaque?" Jang asked. "I would not."

At medical conferences, the elite of cardiology continue to joust over plaque-detection systems, with true believers facing off against naysayers such as Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

"They're barking up the wrong tree," Nissen said. "This has been an elusive target and the chance that any one of these little companies is going to hit a home run here after 15 years of all this discussion is, I think, relatively low.

"Would I like someone to hit a home run and help us figure out where to intervene? The answer, of course, is yes."

Stephen Smith can be reached at stsmith@globe.com.