Interventional radiologists are progressing across a broad front in bringing inventive devices into clinical practice.
For applications designed to treat pathology in the neck, investigators are enthusiastic about the clinical possibilities of stents that may someday replace costly carotid endarterectomy. For treatments in the peripheral vascular system, vendors are optimistic about new catheters that administer clot-busting agents to long stretches of thrombosis.
Among the hottest trends is the marriage of stent and graft technologies used in the minimally invasive treatment of potentially lethal aortic aneurysms, said Dr. Barry T. Katzen, director of the Miami Vascular Institute. The life-saving potential of the new techniques is substantial, considering that 150,000 people in the U.S. were diagnosed with aortic aneurysms last year. Of this total, 44,000 underwent surgery and the rest decided against surgery, partially because of the risks, according to Howard J. Leonhardt, president of World Medical Manufacturing in Sunrise, FL. Between 5% and 10% of patients who undergo surgery to treat aortic aneurysms die on the operating room table.
Early results of human trials indicate that aortic stent-graft placement is safer and less traumatic than surgery. Instead of an eight-day hospital stay, patients undergoing the technique can go home in 48 hours. Recovery is measured in days rather than weeks.
"This technology offers the potential for great patient benefit," Katzen said.
Several trends in endovascular neuroscience are worth watching, according to Dr. Mark H. Wholey, director of diagnostic imaging at Shadyside Hospital in Pittsburgh. The market is expanding, and procedure volumes are increasing. Overall, there are new stents, flexible stents, and better stent expansion. Some experimental stents incorporate drug-delivery devices, while others feature anti-platelet coverings. Still other investigational stent products have been irradiated or feature nodules of radioisotopes to combat restenosis (see "Interventionalists fight restenosis with radiation," page 71).
AORTIC STENT GRAFTS
EndoVascular Technologies of Menlo Park, CA, is moving forward in demonstrating the safety and clinical efficacy of its investigational stent graft in the treatment of abdominal aortic aneurysms. Preliminary results of phase II clinical trials for the tubular configuration of its Endovascular Grafting System were announced in January.
The study found a substantial reduction in mortality, clinical complication rates, and length of hospital stay for patients who underwent the minimally invasive procedure, according to W. James Fitzsimmons, chief executive officer. No deaths or major complications were reported for the 83 patients treated with the EVT graft, while among the 83 patients treated surgically, 4% died, and another 3.3% suffered a major complication, he said.
The EGS device mimics the conventional surgical graft as much as possible, Fitzsimmons said. Both consist of woven polyester fabric that spans the arterial gap weakened by the aneurysm. Rather than surgical implantation, the EGS is transported to the site on a guidewire from a puncture in the groin. In lieu of loop suturing, the interventionalist secures the EGS graft in position by expanding a balloon catheter that impales a series of long hooks into the vessel wall. A self-expanding, stainless-steel-alloy frame also presses the graft against the aortic wall.
EndoVascular Technologies has designed bifurcated and aorto-iliac configurations of the EGS system, according to Fitzsimmons. Phase II clinical trials testing the clinical efficacy of the bifurcated device have reached the midway point, and phase II aorta/iliac trials began in late 1996, he said.
International trials required to gain a CE-mark (the European equivalent of U.S. premarket approval) for the tubular model have been completed.
As of Feb. 1, Leonhardt of World Medical was responding to the final Food and Drug Administration condition that stands in the way of phase II trials of the company's Advanced Talent stent graft system for abdominal aneurysms. Configurations for use in the abdominal and thoracic aorta and modular small-vessel stent spring grafts that extend into the iliac arteries have been approved for use in Australia, Canada, and European and South American countries.
Excluding mismeasurement and operator error, a 95% success rate was reported for the first 65 cases in which the device was implanted to treat subrenal aneurysms of the abdominal aorta, Leonhardt said. The case base includes one instance of a long-term leak and another case in which the patient died when the physician converted to surgery after inadvertently cutting off blood flow to the kidneys. Overall, 92 abdominal aortic implants have been completed since December 1995, he said.
The first application of World's Advanced Talent graft in a thoracic aorta was completed last July. The Australian case involved a 27-year-old gunshot victim whose aorta was grazed by a bullet, Leonhardt said. Another eight successful implants have since been completed.
World's Advanced Talent aortic graft consists of the same Dacron prosthetic material used in surgical grafts. It houses a spring stent composed of a temperature-insensitive blend of nitinol nickel-titanium alloy that is coated with titanium-oxide to resist corrosion. The stent spring exerts up to 240 grams of outward expansion pressure. The top and bottom of the stent release into an open leaflet formation that conforms to vessel shape.
In an experimental configuration, tissue-adhesive packages consisting of microspheres of synthetic and human blood plasma glues are attached to the exterior of the graft. They release their contents when illuminated by operator-controlled intravascular light, Leonhardt said. .
Interventional device market leader Boston Scientific of Natick, MA, is experimenting with an aortic stent graft configuration called the Vanguard. The device features a shaped-memory nitinol stent spring.
Corvita, a Miami-based subsidiary of Pfizer Hospital Products Group, is also a potential contender in this market. It has developed an endoluminal graft that combines a self-expanding metallic stent made from a proprietary elastomeric-spun fiber.
CAROTID STENTS
EndoTex Interventional Systems in Menlo Park is perfecting stents designed for carotid artery implantation. The small, venture-capital-backed firm is assured success even if its stent is adopted as an alternative to only a small portion of the 250,000 carotid endarterectomies performed every year. The rewards could be substantial if EndoTex's minimally invasive technique proves to be as clinically efficacious as surgery.
The investigational protocol involves balloon angioplasty of the carotid artery to eliminate stenosis, followed by installation of a self-expanding stent to assure unobstructed arterial flow and serve as prophylaxis against restenosis.
Because the carotid arteries present special needs, EndoTex designed a self-expanding stent specifically for that application, according to Dr. Michael R. Ross, clinical affairs director. EndoTex uses nitinol to provide the elastic qualities essential for this application.
Mesh size is another important consideration, because soft carotid plaques tend to ooze through the gaps and embolize, Ross said. Care was taken to optimize stent porosity to guard against this "cheese-grater" effect, he said.
Preclinical trials on the EndoTex stent have been completed. The first human trials will commence this year, Ross said.
At least three other companies are developing carotid stents. Cordis Endovascular Systems of Miami Lakes, FL, a division of Johnson & Johnson, is working on a balloon-expandable stent. Schneider USA, a Minneapolis unit of Pfizer Hospital Products Group, has devised a stent that combines self-expansion and balloon assistance to reach its full diameter. Scimed Life Systems, a subsidiary of Boston Scientific in Maple Grove, MN, is also working on a carotid stent project.
Seattle-based NeoRx is examining an investigational pharmaceutical agent that mimics the characteristics of a stent. The concept was inspired by research that found that virtually all restenosis following angioplasty is caused by vascular remodeling, or contraction of the artery itself, according to Dr. Robert Schroff, general manager of cardiovascular products.
The company is testing Biostent, a drug and pharmaceutical delivery system that employs cytochalasin B, an agent that inhibits the contraction of smooth muscle cells. It is delivered to the site by the Microporous Infusion Catheter, an intravascular drug-delivery catheter developed by Cordis.
NeoRx's investigational protocol recommends administration of cytochalasin B after coronary balloon angioplasty with the intent of reducing postprocedural restenosis, Schroff said. Results of completed phase I trials are being evaluated.
DRUG-DELIVERY SYSTEMS
InterVentional Technologies of San Diego is looking at eliminating the pitfalls of intravascular drug delivery with its work-in-progress Infiltrator, a patented balloon catheter that administers therapies intramurally. The device features 21 rows of micro-miniaturized injector ports containing needles that are 1/10,000th of an inch long. When the balloon is inflated, the needles penetrate the lumen, so therapy can be injected into the media cell structure.
The design strategy overcomes the shortcoming of earlier therapy delivery devices, according to Rob Michiels, IVT president. They operate by either shooting drugs against the vessel wall or by trapping the agent against the wall of the lumen.
Animal testing and a European safety study of the Infiltrator have been completed. IVT anticipates gaining a regulatory go-ahead for European sales this year.
AngioDynamics of Glen Falls, NY, began selling a long-length version of its Pro infusion catheters in mid-1996. The devices deliver therapeutic agents over lengths of up to 50 cm, according to Michael P. Cody, corporate communications director. The slits of the Pro perform like valves in that they all open simultaneously, so the drug is delivered uniformly along the entire length of the thrombus, Cody said.
"This catheter opens the potential for being far more aggressive in treating venous clots," he said.
CO2 GAS CONTRAST
AngioDynamics is in the midst of phase II/III U.S. trials of CO2Ject, a carbon dioxide angiographic system. The device is approved for intravascular injection of CO2 for use as a contrast medium during angiographic x-ray applications below the diaphragm.
The technique is extremely safe and inexpensive compared with iodinated contrast media, according to Cody. Because it is a naturally occurring metabolite, no one is allergic to carbon dioxide, he said.
AngioDynamics' engineers needed eight years, however, to determine how to control gas delivery, Cody noted. Safeguards were built into the instrument to prohibit explosive delivery, and patient monitoring was added.
Even a small device can have a substantial impact on the quality of daily practice. That point was reinforced with the introduction of the Burney biopsy needle, following FDA clearance in late 1995. The disposable, coaxial needle system features a sidehole about 1 cm from its distal tip. The side-exiting hole enables the user to rotate the needle to obtain multiple samples from a single needle stick, according to Dr. Stephen M. Stockberger, an assistant professor of radiology at Indiana University in Indianapolis.
Stockberger conducted a controlled test last year that compared the Burney needle's performance with the diagnostic yield of conventional coaxial devices. Diagnostic material was obtained in all 27 patients biopsied with the Burney needle, while the diagnostic rate of the conventional needle system was 84%, he said.
The Burney needle is manufactured by Promex, a small, privately held firm in Indianapolis. It is available with an 18-gauge introducer and a 23-gauge biopsy needle, or a 19-gauge size with a 25-gauge biopsy needle.
