It's a medical marketer's dream: Offer a safe implantable blood pump for patients dying from end-stage heart failure. With nearly 5 million Americans suffering from that disease—and another 400,000 new cases diagnosed each year—experts have pegged the potential market for ventricular-assist devices (VADs) at 70,000 in the U.S. alone.
At a price of $75,000 to $100,000 per device, the payoffs for companies with superior VAD designs are obvious. Yet, 25 years after the National Heart Lung and Blood Institute began funding research, manufacturers are still trying to clear obstacles blocking widespread use of the devices. Among the challenges:
Design VADS that are smaller, more durable, and pose less risk of infection, stroke, and other complications.
Improve the quality of life for VAD patients with systems that are easier to operate and maintain.
Gain the confidence of cardiologists, who must decide whether a VAD is preferable to medication and other therapies.
Spend tens of millions of dollars to conduct clinical trails and assemble the data to get marketing approval from the Food and Drug Administration (FDA).
Add up those hurdles, and you get total VAD procedures of just 1,500 a year in the U.S., estimates Philip Miller, VP of research and development for California-based WorldHeart, who delayed his honeymoon in 1984 to spend time with the first patient to receive a Novacor VAD. Still, Miller remains optimistic. "This technology is on the cusp of the anticipated market really taking off," he says.
Goal: a viable destination therapy
One reason for the slow adoption of the technology is that, until 2002, when the FDA approved Thoratec's HeartMate XVE system for "destination therapy," VADs could only be implanted in U.S. patients on a temporary basis, either to help a patient recover from heart surgery or to assist those awaiting a heart transplant. Implanted in the abdomen, the 2.5 lb., electrically-powered XVE attaches to the aorta and left ventricle. A flexible tube passes through the skin to connect the implanted pump to an exterior controller.
Only about 2,100 transplants occur in the U.S. each year, a fact that further underscores the need for VADs to be prescribed as permanent devices, say device makers. Thousands die as they wait for a donor heart—and thousands more do not qualify for transplants because of age or other health problems, such as a cancer.
WorldHeart is working on a fully implantable version of its Novacor VAD. The implant receives power through a transcutaneous system.
Currently, major competitors to Thoratec are conducting clinical trails to demonstrate to the FDA that their devices compare favorably to the HeartMate for destination therapy, based on patient survival rates, quality of life, device durability, and cost effectiveness.
For example, WorldHeart's clinical trails will track 200 patients who receive the Novacor I versus 100 who get the HeartMate VAD. Like the HeartMate, the Novacor is a pulsatile device, which mimics the natural heart by employing a polyurethane blood sac that contracts and relaxes. About 1,500 patients have received the Novacor system, approved for bridge to transplant since 1998, including one who used the device for more than six years.
Also targeting destination therapy applications, Houston-based MicroMed Technology is measuring its DeBakey VAD—a dramatically different design—with the HeartMate in clinical trails of some 360 patients. Unlike the Thoratec and Novacor pulsatile devices, the DeBakey VAD pumps blood on a continuous basis. About the size of a "C" battery, it weighs only 4 ounces and features only one moving part—an inducer/impeller that spins at 7,500 RPM and generates blood flow in excess of 10 l/min.
"With its compact size, the VAD doesn't need to sit in a patient's abdomen, which can be uncomfortable and cause problems with digestion," notes Bob Benkowski, MicroMed VP of engineering, who began working on the VAD when it was a NASA project in 1990.
Dr. James Kirkin, director of heart and lung transplantation at the University of Alabama Birmingham hospital, says that he has chosen the DeBakey VAD for his patients because of its "ease of implantation, reliability, small size, and quiet operation." Earlier this year, Kirkin implanted the 300th Debakey VAD, which has gained the CE mark in Europe.
Smaller + simpler = better
Market leader Thoratec, too, is competing against itself in clinical trails that will test the outcomes of patients receiving its new HeartMate II, a continuous flow design weighing 14 oz, against its own FDA-approved XVE. "We've turned the corner on this technology, and what it will really take to kick things off are smaller, less-invasive devices with proven durability," says Ken Butler, a Thoratec senior technical advisor who has worked on VADs since 1984. He adds that Thoratec engineers are already working on a lightweight, fully implantable VAD. Key features: a magnetically-levitated centrifugal pump and a transcutaneous power system. Current VADs, with electric lines extending through the skin, pose a constant risk of infection, doctors say.
Critics claim that the first generation pulsatile devices incorporate too many moving parts—bearings, cams, and pump sacs—that add weight and raise concerns over wear and reliability. In the landmark REMATCH trials, which compared patients who received the HeartMate XVE with a control group on traditional drug therapies, VAD patients had a survivability rate after one year of 52.1 percent—more than double the rate of non-VAD patients. However, the study also found a significant incidence of device failures during the second year.
"The first-generation HeartMate clearly has limited durability," says Dr. Robert Jarvik, who grabbed headlines in 1982 when his total artificial heart was implanted in dentist Barney Clark. "For VAD technology to be accepted, the public needs a device with at least a five-year proven reliability."
In July, Jarvik Heart, Inc. received FDA approval for clinical trials of the Jarvik 2000 FlowMaker rotary pump as a bridge to transplant. Several other U.S. and foreign companies also are seeking initial BTT approval for miniature, impeller-style designs. In Europe, where the Jarvik 2000 has the CE mark, Peter Houghton of England has led an active life supported by the device for nearly 5 ½ years. "We've never had an incident of a broken blood pump," states Jarvik.
On the downside, the newer rotary devices may pose more of a risk of stroke and blood clots, says Dr. Lee Goldberg, a cardiologist at the Hospital of the University of Pennsylvania. Result: most patients will need to take anticoagulant medication.
Winning the medical community
Besides a better track record on device durability, medical manufacturers must demonstrate that their VADs deliver a higher quality of life for patients. "As cardiologists see more and more patients who were terribly sick and can now live near-normal lives because of a VAD, they are going to be much more accepting of these devices," says engineer Gerson Rosenberg, who heads artificial organ research at Penn State's College of Medicine in Hershey.
A major frustration, observers say, is that FDA has so far permitted VADs to be implanted only in patients for whom all other medical alternatives have been exhausted. "We've been putting these devices in patients who are already half-dead when the surgeon opens up their chest," notes Goldberg of the University of Pennsylvania Hospital.
Ultimately, as VADs prove more reliable, the FDA will need to permit clinical trails with younger and healthier patients. Favorable results from that experience will help gain the confidence of cardiologists not just at the premier medical centers but at hospitals all over the country, predicts Butler of Thoratec.
Costs also are a concern, both for device makers and patients. Annual funding from the National Heart Lung and Blood Institute for artificial hearts—now at around $7.5 million—is less than a third of what it was a decade ago, and much of that money is directed to new devices for infants and children. On the plus side, Medicare and Medicaid patients can now get substantial reimbursement for VAD costs.
Given these developments, how long will it be before annual VAD procedures reach that long-anticipated 70,000 number? The consensus from experts: at least another decade.