The Heart of the Industry

Device Manufacturers Look to Create the Next Generation of Yesterday’s Superstar Performers With Advanced Technology

Paula DeJohn
Contributing Writer

Farlow’s Scientific offers anatomically correct glassblown models, such as the one shown above, for demonstrating products and procedures or for R&D of new designs. Photo courtesy of Farlow’s Scientific Glassblowing, Inc. Photography by Harte Robba.

With heart disease now acknowledged as the primary cause of death in the United States, it is no surprise that the scientific community has been stepping up the pace of research, developing new devices and procedures and refining old ones. According to the American Heart Association, 2,400 Americans die of cardiovascular disease each day—a number higher than the combined number of deaths from respiratory disease, diabetes and accidents.

But given the publicity attached to every stent failure and implant defect, it may surprise some that overall, the outcomes for heart disease are improving dramatically.

An international six-year study conducted at the University of Edinburgh that followed 45,000 patients with heart problems revealed that the worldwide death rate was reduced by nearly half over the years of 1999 to 2005 (for more information on the study, see the May 2 issue of the Journal of the American Medical Association).

Perhaps part of this reduction can be attributed to the rapid growth of the market for complex cardiovascular treatment devices. Research firm Frost & Sullivan, based in Palo Alto, CA, has estimated that the cardiac device market in North America was $17.88 billion in 2005 and will grow to $40.46 billion in 2011. Researchers attributed part of that growth to the need for more products to serve the aging population, but they also cite the demand for less invasive—and less expensive—treatment from patients and insurers.

Cardiovascular technology is heading in many directions, based on clinical trials and announcements from start-up companies and the observations of component manufacturers as they review orders from OEM customers. Trends include ever-smaller components, use of space-age materials, combination products that marry devices with drugs, robotics and new applications for less invasive surgery. Following is a look at some recent advancements within major cardiovascular technology categories.

Catheters

Angiography and angioplasty combine radiology and cardiology in a procedure that is performed under X-ray guidance in the cardiac catheterization laboratory. A wire, followed by a PTCA catheter, is inserted through the femoral artery in the groin (or sometimes the arm) and pushed through to the heart. A contrast medium is injected through the catheter to permit X-ray images of the heart and arteries. If a blockage appears, the balloon is inflated to open the vessel.

Only about 950 hospitals nationwide have cardiac catheterization laboratories. Most cardiac catheter models currently sell for between $200 and $300, according to published surveys.

The concept of catheterization to diagnose heart problems dates from the 1930s. Using catheters to treat those conditions came much later. In 1980, Murray Hill, NJ-based C.R. Bard introduced its first balloon catheter for percutaneous transluminal coronary angioplasty (PTCA). Other companies followed suit and now, along with Bard, the big cardiovascular companies—eg, Natick, MA-based Boston Scientific and its recent acquisition, Guidant; Minneapolis, MN-based Medtronic; and the Cordis division of Johnson & Johnson, based in New Brunswick, NJ—dominate the market. Together, Indianapolis, IN-based Guidant and Boston Scientific claim about 68% of the market.

While new brands, such as Guidant’s Voyager line, have entered the market in this decade, the catheter market generally is considered mature. However, the ways in which these products are being used have shifted. While catheters historically were used for diagnosis, now they also are used to deliver treatment, such as stents—in turn, other imaging technologies, such as magnetic resonance, have played a larger role in diagnosis.

According to a Feb. 25 New York Times article, nearly one million US patients received stents in 2006, while the number of bypass surgeries decreased by a third in the past decade. However, the article notes, concerns regarding stent safety—such as risk of blood clots—has led some clinicians to predict a resurgence of the more-invasive bypass procedures.       

Ralph Joiner, vice president of sales and marketing for Grass Valley, CA–based Farlow’s Scientific, a manufacturer of catheterization components, said he does not see any threat to the catheter market, from stent issues or new technology. “It will be a long time before anything replaces catheters,” he said. “I still firmly believe there are applications where you’re going to have to use a balloon.”

Catheters are serving other purposes in the cardiovascular market as well. For example, they serve in the treatment of structural heart defects, such as the use of valvuloplasty to open non-functioning cardiac valves or implantation of devices to close holes in the heart wall.

Outside the heart, catheters are used in procedures that help diagnose and alleviate peripheral vascular disease. The New York-based Cardiovascular Research Foundation estimated that 10 million Americans suffer from this condition, a chronic deficiency in blood flow to the limbs caused by a buildup of fatty plaques on vessel walls. FoxHollow Technologies, based in Redwood City, CA, put that estimate at 12 million.

That company is no stranger to this market. In June 2003, the FDA approved FoxHollow’s SilverHawk plaque excision system for use in peripheral vessels. Now the company is seeking approval for cardiac use as well. The SilverHawk is a device that removes plaque by scraping it away with a catheter-driven blade, rather than compressing it against the vessel wall, as do balloons and stents.

Electrophysiologists use catheters to aid in the diagnosis and treatment of cardiac arrhythmias (irregular heartbeats). Biosense Webster, based in Diamond Bar, CA, produces ablation catheters used to destroy cardiac tissue that causes arrhythmias. At the annual Heart Rhythm Society (HRS) conference held in May, Biosense announced it would collaborate with Medtronic on a product development program to create new technologies for treatment of arrhythmias. Medtronic spokeswoman Kyra Schmitt said the collaboration likely would focus on merging Biosense Webster’s cardiac mapping technology with Medtronic’s implanted devices.

Bard, which also produces electrophysiology catheters, demonstrated the company’s latest refinements at the HRS conference. These included the Scorpion ablation catheter, capable of bidirectional tip orientation and more flexible curve settings for more accurate tissue mapping and delivery of electrical contact. Other Bard innovations include a steerable sheath, which will allow doctors to maneuver the catheter more easily, and the company’s ElectroView three-dimensional heart mapping software.

Currently in clinical trial is a device, delivered by a catheter, designed to close defective mitral valves to treat blood regurgitation that makes the heart work harder. Called MitraClip, the device is made by Evalve Inc., based in Redwood City, CA.

According to Ajay Kirtane, MD, an assistant professor of clinical medicine at Columbia University Medical Center in New York and a faculty member of the Cardiovascular Research Foundation (CRF), valves themselves could be replaced via catheter in the future.

Aiding the innovators of catheterization technology today are component manufacturers, who often provide OEMs with items such as tubes, tips, balloons and guidewires.

One company contributing molds and tips for most of the “major brands” is Farlow’s Scientific. Customers include “everyone in the world,” according to Joiner. The company employs a staff of professional glassblowers who make small glass tubes that an OEM can use to hold the ends of two tubes of different materials. Heating the glass compresses the tubes to form a butt seal. Farlow’s Scientific also makes molds for catheter tips. “Some use metal,” Joiner noted, but many prefer glass because “you can see what you’re doing, it has a relatively low cost and it’s clean.”

Another component of catheters and other heart devices is wire, fabricated by specialty firms such as Wytech, based in Rahway, NJ. Wytech makes core wire for PTCA guidewires, made of soft, flexible stainless steel tipped with platinum so it is visible on X-rays. Paul Dowd, the company’s vice president of sales and marketing, predicted that more catheters and other devices will take advantage of the properties of nitinol for specialized wires. The reason, he explained, is the material’s extreme flexibility and its “shape memory” that allows it to return to a preset shape after distortion.

“That’s the thing people really love to play with,” Dowd said.

Nitinol, an alloy of nickel and titanium, was developed for military and industrial use but is becoming more popular for medical use, such as guidewires that can pass through complex channels in the body yet avoid kinking or bending.

Stents

Stent technology is another booming segment in the cardiovascular market. Published reports value the US cardiac stent market at about $3 billion, with Boston Scientific and Johnson & Johnson sharing $2.9 billion of that total.

Today, stents are available as either a bare-metal product or one that is coated with a drug. The market has been in flux with the selection of these products, though, given all the longitudinal studies presenting mixed results about some of the newer technology. Ever since the landmark event of April 2003, when the FDA approved Cordis’ Cypher sirolimus-eluting stent—the first drug-eluting stent approved in the United States (they have been used in Europe for a longer period)—bare-metal stents have taken a back seat in demand, and prices have slid downward accordingly. The market for drug-eluting stents has grown even larger, thanks to the 2004 US approval for Boston Scientific’s Taxus stent, which is coated with the drug paclitaxel.

Other companies also have developed variations using different drugs and different configurations. The latest is from Xtent, based in Menlo Park, CA. In an ongoing trial that began in December 2005, Xtent has been testing its NX DES system, designed to deliver multiple drug-eluting stents using a single catheter. The NX also can handle longer stents—during the trial, a doctor inserted a single 52-mm stent, the longest stent ever placed in coronary arteries from a single catheter, the company claims.

Johnson & Johnson was less successful in a trial of one of its newer stents. In May, the company ended testing of its cobalt-chromium CoStar II model (made by recent acquisition Conor Medsystems, based in Menlo Park, CA). In comparison with Taxus, the CoStar failed to measure up, and Johnson & Johnson pulled it off markets in other countries and cancelled its application for FDA approval. CoStar also used paclitaxel as a coating, and additionally carried the drug in reservoirs embedded in the wire mesh. However, the dosage was insufficient, according to statements from Conor and Johnson & Johnson, and they announced plans to switch to a sirolimus coating before resuming CoStar development.

Where does the future hold for stent technology? Joiner of Farlow’s Scientific predicted that the industry likely will see stents made of some biodegradable material that will be safer and more effective than what’s currently available.

Other Implantable Devices

Pacemakers are big-ticket items, and technology improvements are rewarded with price increases. According to a 2004 survey published in the newsletter Hospital Materials Management, hospitals that purchased pacemakers spent an average of $4,884 per licensed bed on them, an increase of 74% from the previous year, primarily due to newer technology.

That year, the average price of a single-chamber pacemaker was $3,500. Dual-chamber models averaged $4,000, and leads cost $500 on average.

A single-chamber pacemaker has one lead that is attached to an atrium or ventricle and set to a standard rate. The dual-chamber version has two leads, usually attached to an upper and a lower chamber, set to keep both beating at the same rate.

Pacemakers are programmed to maintain heart rate by responding to criteria such as body movement or oxygen consumption. They perform the function of the heart’s sinus node, which regulates heartbeats. The power source for most types is a battery connected to an integrated circuit, and encased in titanium or another bio-inert metal. Leads may be unipolar or bipolar and are connected directly to the heart wall. The entire device weighs about 33 grams (1.16 oz.).

Medtronic, Boston Scientific (through its Guidant division) and Minneapolis, MN-based St. Jude lead the pacemaker market in terms of sales.

Although pacemakers long have been used in patients with heart problems, refinements continue to be made with the technology. For example, many of the top manufacturers in this market are focusing on remote monitoring. In April, Medtronic completed a case study demonstrating its CareLink system. Using wireless technology and customized programming, the system can notify, via voice messages, a physician when a patient’s vital signs reach levels that could trigger atrial fibrillation.

The Zephyr pacemaker is one example of how technology is evolving. This model was designed to automatically perform all standard follow-up testing before a patient arrives at a doctor’s appointment.  In addition, it’s the first pacemaker that can, in about 90 seconds, tell physicians which device timing settings are optimal for each patient’s needs. Photo courtesy of St. Jude Medical.

Similarly, St. Jude offers an Internet-based remote data transmission system called Merlin. The system transmits device data to the patient’s electronic health record, which also is part of the Merlin system.
On May 3, almost concurrent with the HRS conference, St. Jude received FDA approval for its Zephyr pacemaker line. The Zephyr adds a new capability: a programming feature, called QuickOpt, which computes ideal timing settings in about 90 seconds. The company said this feature saves the time and cost of echocardiography, the current method of verifying timing cycles.

St. Jude Medical also recently unveiled a new insulation material for cardiac leads (used with pacemakers). Named SPC, the hybrid material combines silicone rubber and polyurethane. Based on two years of animal studies, St. Jude said SPC appears biostable, with almost no degradation. If further studies are successful, the material could replace the polyurethane 55D currently popular in leads.

For Oscor, a 25-year-old company based in Palm Harbor, FL, working with wire often means producing leads for pacemakers and other implantable devices. Bethania Tavárez, Oscor’s director of sales and business development, said her company produces molds and metal products for many of the large OEMs that have introduced the latest implantable cardiovascular technology available. The company produces leads for cardiac pacemakers, defibrillators, neurostimulation devices, biosensors and other implantable items.

Minneapolis, MN-based Enpath Medical, which also makes leads for pacing, currently is helping develop a new connector standard for the industry.

Along with pacemakers, the other major category in cardiovascular technology is implantable cardioverter defibrillators (ICDs). Medtronic, Boston Scientific/Guidant and St. Jude lead this market as well.

Problems with leads and electronic defects, as well as reports of overuse in patients who may not need them, gave ICDs a black eye in recent years, and recalls have dominated the press in the past two years. The news isn’t all bad, though. A new report from the Minneapolis Heart Institute, released May 10, indicated the newest devices are more reliable and last longer. The study, which compared ICDs implanted from 2004 to 2006 with earlier models implanted between 2001 and 2003, found that between those periods, longevity increased by 26% for dual-chamber ICDs and by 36% for single-chamber models.

To help in future monitoring, the industry established the National ICD Registry in September 2004. First-year results from 1,450 participating hospitals tracked 100,000 patients and were accepted as a benchmark by the Centers for Medicare and Medicaid Services (CMS).

In spite of the problems the ICD market has faced, manufacturers continue their quest to create innovative next-generation products. One of the latest ICD technology involves an implant system with devices that automate cardiopulmonary resuscitation (CPR) and give electronic feedback to practitioners. Zoll Medical Corporation, based in Chelmsford, MA, includes CodeNet software with its ICDs. This software powers the AutoPulse automatic compression device, as well as records compression results when clinicians administer manual compressions. One package Zoll currently markets to hospitals includes two wireless PDAs; two R Series defibrillators with pacing; a case of electrodes; an AutoPulse unit; and a case of LifeBand compression devices.

A case study shows automated CPR is successful. The Richmond, VA-based Ambulance Authority compared 499 manual CPR cases and 284 cases using automated CPR via AutoPulse. The study reviewed out-of-hospital cardiac arrest cases between January 2001 and March 2005, after paramedics started using the AutoPulse. The rate of survival until hospital discharge rose to 9.7% using automated CPR, compared with 2.9% using manual chest compressions.

What’s Ahead

In the future, companies will collaborate more closely with their outsourcing partners, according to Accellent Executive Vice President Patrick Fabian, who noted that the company , an outsouring provider in Wilmington, MA, has its own design team and procedures in place to build a product from design to packaging. “We are seeing a clear trend toward more development work and complete device opportunities and less of a focus on simple component manufacturing,” he said.

Another trend is increasing complexity in the final products. The market for convergent technology—a combination of a device and drug or biologic—will continue to grow in the cardiovascular realm. For example, future cardiology procedures could involve products such as inhalation devices for drug delivery and liquid sutures.

“Companies that are historically device companies are now starting to get into drugs,” according to Carl Martin, CEO of Millersburg, PA-based Advanced Scientifics, a provider of disposable products (eg, IV bags and packaging) used during cardiovascular surgery. Martin said more of his clients are working with both devices and drugs.

The road ahead will not be smooth, though. Martin noted that the growth in the combination market continues to challenge the FDA, since it traditionally has separated those categories in its review process.

Kirtane of the CRF sees additional problems with the way devices are approved in this country. The FDA, he noted, is testing for efficacy, and since most new devices are expensive, the sample size is kept small. However, large samples are required to measure safety. That “conundrum” accounts for some of the well-publicized failures of devices that have been cleared for use by the FDA, he said.
In addition, he noted, “There’s a dissociation between what the FDA approves and what CMS is willing to pay for. That’s a little frustrating for physicians and for patients.”

Joiner of Farlow’s Scientific noted that the device industry could be challenged in times to come as drugs play a larger role in the treatment of cardiovascular problems and, in some cases, replace surgery for treatment. However, he also predicted that med-tech manufacturers will have new opportunities as the use of robots for cardiac surgery increases. This sophisticated equipment can work with much smaller incisions, he noted.

The future of implantables may rest in the addition of diagnostic capabilities. For example, Medtronic is focusing on developing devices that incorporate diagnostic tools with therapy. “We have been quite active as a company in the field of detection and diagnosis,” Schmitt said.
Ideally, she added, a device implanted in a patient with diagnosed heart failure could measure changing conditions before symptoms (such as increased fluid in the heart cavity) appear and alert physicians using remote monitors. “This is a new area, certainly, in [atrial fibrillation] management,” Schmitt said.

Medtronic and other industry members also are developing devices that could combine the functions of ICDs with those of pacemakers. For example, future implants could detect an abnormal heart rhythm before it reaches the point where the patient needs a shock, and they instead could regulate the heartbeat in the same manner as a pacemaker.

With the rapid advances in technology, combined with associated competition and regulation along with increasing public scrutiny, the stakes are high for OEMs and their outsourcing partners. As a clinician who participates in trials of the latest devices, Kirtane understands the manufacturers’ dilemma. “It’s always good to have public awareness,” he said, “but there’s often a gap between the sound bites and actual research that’s going on.”

He urged companies to provide as much data as possible to independent researchers—such a strategy could have helped avoid recent controversies over stent efficacy and ICD failures (for example), he believes.

While protecting proprietary information is important, he added, the industry has a responsibility not only to shareholders but also to the public. By enabling independent studies, innovators can avoid some of the public and investor concerns surrounding new products, Kirtane advised. “Transparency is going to be critical,” he concluded.

Paula DeJohn has written about manufacturing and healthcare supplychain topics for more than a decade, and has served in editorial positions at Wire Journal International and Hospital Materials Management. She lives in Aurora, CO.