August 5, 2009
Across the River Thames from London’s Big Ben tower, Martyn Thomas repairs broken hearts.
Thomas, a cardiologist at St. Thomas’ Hospital, fixes diseased heart valves in a way that allows patients to avoid open-heart surgery. The technique employs devices made by Medtronic Inc. of Minneapolis and Edwards Lifesciences Corp., based in Irvine, California. The two companies are racing to bring the technology to the U.S., the key to a worldwide market Medtronic says may top $2 billion annually within five years.
The method may aid as many as 10,000 patients this year in Europe, where regulators allowed the devices on the market without clinical trials for the weakest patients. Doctors there are years ahead of their American counterparts, who must await research results and U.S. approval before using the valves.
“This is a mind-boggling technology, where patients come in very sick and they walk out of the hospital with an excellent quality of life,” said Rob J.W. ten Hoedt, Medtronic’s head of European and Central Asian operations. “Europe is having a party with these new products.”
Medtronic rose 28 cents, or 0.8 percent, to $36.20 yesterday in New York Stock Exchange composite trading and has fallen 31 percent in the 12 months before today. Edwards fell 1 cent to $64.93 and has gained 4.4 percent in the past year.
The U.S. Food and Drug Administration will make approval contingent on a study to prove the valves are at least as effective, and as safe, as traditional care. Doctors in the U.S. recognize the FDA’s need for caution, said Murat Tuzcu, an interventional cardiologist and vice chair for clinical operations at the Cleveland Clinic.
“There is an untapped population, and this technology may open the floodgates in the U.S.,” Tuzcu said in an interview. “We need to get the information, and the FDA’s rigorous oversight is going to give us the best data.”
Traditional repair requires surgeons to stop the heart and make an incision running the length of the chest to get access to the valve that controls the flow of oxygen-rich blood to the body. The narrowed and calcified aortic valve is cut out, and a $5,000 replacement is sewn into place. The surgery is effective, with valves lasting 15 years or longer, said Larry Wood, Edwards’s corporate vice president of transcatheter valve replacement.
Thomas, an interventional cardiologist and valve pioneer, instead threads a specially designed $25,000 valve into a beating heart through an artery in the leg or a small incision in the ribs. In some cases, the heart is directly pierced at the apex with a hollow-nosed needle, allowing doctors to insert a guide wire and wind it through the organ’s chambers. The replacement valve, crimped onto a catheter, follows the wire as it is fed into place.
The procedure has been performed for less than five years, leaving questions about the comparative safety of the surgery and the durability of the valve, which must open and close 40 million times a year. Medical regulators in Europe limit the operation to patients who can’t easily tolerate open-heart surgery to repair their diseased valves.
“This is a lethal condition, with a 50 percent annual mortality rate,” Thomas said. “The real skill, especially at this early stage, is picking a patient who will survive the procedure and then will also thrive.”
European Union regulators, who set rules for 27 countries, cleared the devices from Edwards and Medtronic in 2007. The valves may generate $200 million in sales this year in Europe, the only place where they are approved, according to forecasts from Medtronic and Edwards. The world market will be larger, the companies say.
“There is no doubt this is a $2 billion to $2.5 billion market in the population we have today,” mainly patients older than 75 and others who couldn’t tolerate open-heart surgery, ten Hoedt of Medtronic said in an interview. “If we go younger, to age 65, that market opportunity will grow exponentially.”
Surgeons are still unsure of the death and complication rates, including strokes, aortic rupture, bleeding and migrating valves, in patients who undergo the procedure. A registry tracking patients in Europe showed a 78 percent survival after one year in patients getting the valve through an artery, and 50 percent for sicker patients treated through the ribs.
Edwards began a clinical trial of its Sapien valve in 2007, putting it at least two years ahead of its main rival, Medtronic’s CoreValve, in progress toward the U.S. market. The results may be available next year, according to Edwards’s Wood.
The procedure relieves symptoms for patients who don’t qualify for a traditional operation, Thomas said. Researchers are studying whether it will prolong life and reduce subsequent medical costs by helping patients avoid repeated hospitalizations as the disease worsens, he said.
With aortic stenosis, the heart struggles to pump, causing pain, fainting and heart failure, according to the U.S. National Institutes of Health, based in Bethesda, Maryland. Four percent of octogenarians have the condition, and the number of patients will continue to grow as the population ages, Thomas said.
The recovery period with the minimally invasive approach is easier, with patients typically walking within a day of surgery and returning to normal life without months of rehabilitation, doctors said.
There are 254,000 aortic valves replaced worldwide each year, including 105,000 in Europe, according to Toronto-based Millennium Research Group. Almost one in 10 European patients now gets the new aortic valves, said Larry Biegelsen, an analyst at Wells Fargo Securities LLC in New York. About 40 percent of all aortic valve replacements may be done without chest-cracking surgery by 2014, he said in a telephone interview.
Patients getting the valves undergo heart manipulation to speed up the beating and wring out blood, Thomas said. The process makes it easier to position the replacement on top of the existing valve without stopping the heart and putting the patient on a heart-lung bypass machine, he said.
A study, published in the Journal of the American College of Cardiology in May, showed the new devices help the heart pump out more blood than the older models that are sewn into place. The improvement may stem from a larger opening inside the newer valves, which don’t have an internal ring needed to hold the stitches in place, said Edwards’s Wood.
As physicians learn more about the less-onerous treatment option, they are sending more patients for evaluation by cardiologists, Thomas and other doctors said. Aortic valve procedures in Europe grew about 9 percent last year, about three times the usual rate, Wachovia’s Biegelsen said.
“It was a sleepy market before,” Biegelsen said. “The transcatheter technology is expanding the market.”
The procedure requires cooperation between half a dozen interventional cardiologists, heart surgeons, anesthesiologists and imaging experts, plus nurses and technicians to get the valve positioned correctly. Cardiac surgeons, who cut open the chest, participate in each operation at St. Thomas. So do their traditional rivals, the interventional cardiologists who work through small incisions.
Surgeons typically oversee the operation when a slit is made between the ribs and the heart is pierced to insert the valve. The puncture is closed like a sack, with drawstring stitches the surgeon puts in place before the procedure. Interventional cardiologists lead the way when the valve is threaded through the artery in the groin up to the heart.
The new valves cost about $25,000, about five times the price of the traditional models. The price takes into account the cost of developing a new technology and the training and supervision needed when physicians first start doing the procedure, Edwards’s Wood said. The first year the devices were sold in Europe, a company specialist was present to assist at each operation, he said.
The complete cost of doing the procedure, including the recovery time in the hospital, is likely to be about the same in the U.S. as for traditional operations, Wood said. While the valve costs more, it results in speedier surgery, less need for other equipment such as heart-lung bypass machines, and fewer days in the hospital, he said.
The valves are the first generation to use the less- invasive, catheter-based approach. Other devices in development could be more easily inserted and manipulated, allowing doctors to reposition them during the procedure whereas the current devices can’t be moved after they are installed.
Boston Scientific Corp. made an equity investment, for an amount not publicly disclosed, in Sadra Medical, a closely held company founded in 2003 in Campbell, California. Sadra is developing an aortic valve system known as Lotus that can be implanted through the circulatory system and repositioned as needed.
U.S. regulators are “going to want to know that these valves last for 10 years, as the surgically implanted valves do,” James Tobin, who retired in July as chief executive officer of Natick, Massachusetts-based Boston Scientific, said in an interview. “Our position is, let’s hold our fire on the first-generation stuff and wait until the better solutions are at hand.”
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