Edwards Lifesciences in Irvine has been making artificial heart valves since 1960, so it thought it knew the ins and outs of treating valve disease.

But since 2004 it has run into many surprises — some encouraging, some upsetting — as it worked on a system for implanting valves without open-heart surgery. (VIDEO: CLICK HERE to watch a video explaining Edwards valve-replacement systems.)

One of the biggest discoveries was how much it had to overhaul the technology, which it purchased as part of a $125 million-plus corporate acquisition.

Another revelation was how many people might want the product if the Edwards catheter system for heart valves lives up to its potential.

"There's a large untreated patient population," says Larry Wood, corporate vice president in charge of catheter-implanted heart valves at Edwards. "That was a bit of news to us as a No. 1 heart-valve maker."

Edwards knew that while about 100,000 patients have open-heart surgery in the United States each year to replace failing valves, another 100,000 need new valves but don't get them. The main reason: Their health is too poor for major surgery, which makes them candidates for a catheter-based system.

Then in 2005 and 2006, medical researchers found that even more patients suffer from valve disease. Two studies revealed valve malfunctions in a third or more of elderly patients who undergo stress tests, even though they had no symptoms otherwise.

Although Edwards hasn't released an estimate of how much it could gain from commercial success of what it calls the Edwards-Sapien valve system, it's vying for what's potentially a multi-billion-dollar market.

EARLY PROBLEMS

Unpleasant surprises occurred soon after Edwards acquired the catheter system in its 2004 purchase of Percutaneous Valve Technologies Inc. of Fort Lee, N.J.

The system had been developed by a PVT subsidiary in Caesarea, Israel, and by interventional cardiologist Alain Cribier of Rouen, France, who used it to implant the first aortic valve through a catheter in 2002. He inserted the catheter through a vein in the leg, threaded it upward to the heart, following the direction of blood flow, then twisted it through the chambers of the heart to the aortic valve.

Cribier, with more than 10 years of experience using balloon catheters to treat calcified heart valves, had repeated successes with that procedure. But when initial trials conducted by other doctors began in the United States, a number of the first patients died. Edwards decided it needed to intervene.

In mid-2005, it halted the trials and began making changes.

Edwards concluded that Cribier, as a pioneer of balloon-catheter surgery, was able to succeed in procedures too difficult to teach to other doctors, Wood says.

So, it changed Cribier's tortuous route through the heart to the aortic valve, which sometimes caused damage to other heart valves along the way. The new route was against the direction of blood, but more direct – from a leg artery up to the aorta and through it to the aortic valve.

Since restarting the feasibility trials in early 2006, results have been more encouraging. At hospitals in New York, Cleveland and Dallas, 55 gravely ill patients with an average age of 82 received catheter-delivered implants of Edwards heart valves. After 30 days, only about 7 percent had died, compared to a projected 33 percent if they had open-heart surgery.

Such results are part of the reason why Vasilis Babaliaros and Peter Block of the Emory University School of Medicine call the Edwards and CoreValve devices a "drastically improved" technology.

CONTINUAL CHANGE

With a staff of 100 working on the technology in Irvine and Israel, Edwards keeps improving the technology.

New tissue. The valves had been made from the pericardial membrane surrounding a horse's heart. Now, like other Edwards valves, they're made of pericardial tissue from cows.

That means they can run through the same quality tests that Edwards uses for other tissues, including a computerized measure of thickness, mechanized dye-cutters to assure standard sizes, anti-calcification treatment, and a test to make sure that the three leaflets in each valve have matching elasticity.

New catheter features. In the Edwards Retroflex system, the catheter contains a lever that allows the cardiologist to curve the catheter tube to follow the curve of the aorta.

Two routes instead of one. Edwards has devised a second new route for a catheter to follow – through a small incision between the ribs and through the apex, or tip, of the heart. This system, called the Ascendra delivery system, is for patients with arteries too narrow or diseased for the Retroflex catheter.

"We've been making heart valves (of bovine tissue) since 1982, so we apply all our experience," Wood says.

Based on those improvements and the results it has achieved with a total of 300 catheter-delivered valve implants worldwide, Edwards anticipates receiving approval to sell its system in Europe by the end of this year.

It hopes for approval from the FDA by this month for a randomized clinical trial. If all goes well, approval to market the Edwards-Sapien valve system in the United States could come by 2010.