A CDU

At the 16th annual Transcatheter Cardiovascular Therapeutics (TCT) meeting in Washington in late September, companies big and small presented compelling data from various studies for new products that they hope will lead to newly approved products in the interventional cardiology sector as well as showcased recently cleared devices that could potentially revolutionize the medical field.

Conor Medsystems (Menlo Park, California) unveiled preliminary results from its COSTAR I clinical trial. The COSTAR I study, planned to include up to 130 patients, is designed to evaluate the safety and performance of four formulations of paclitaxel loaded on Conor's COSTAR cobalt chromium stent. The principal investigator for this study is Upendra Kaul, MD, of the Batra Hospital and Medical Research Center (New Delhi, India). The initial results are for one of the four formulations, a 10 mcg dose (per 17-mm stent) released over approximately 30 days. A total of 57 lesions were treated in 40 individuals from a complex patient population.

More than 50% of the patients had a prior myocardial infarction and 28% were diabetic. Other complex characteristics of the patient group included small-diameter coronary vessels and long lesions, with an average reference vessel diameter of 2.46 mm and an average stent length of 22.3 mm.

At four-month follow-up, the in-stent binary restenosis rate for this group of patients was 1.9%. For lesions treated with a single stent, the in-stent angiographic late loss was 0.40 millimeters, and the in-segment late loss was 0.21 millimeters. The volume obstruction by intravascular ultrasound was 7.1%, and the target lesion revascularization rate was 1.8%.

Conor Medsystems develops controlled vascular drug-delivery technologies. It has initially focused on the development of drug-eluting stents to treat coronary artery disease. Conor's stent design incorporates hundreds of small holes, each acting as a reservoir into which drug-polymer compositions can be loaded.

In another presentation at TCT, AccessClosure (Mountain View, California) said results from its MatrixVSG System Pivotal Trial met its safety and effectiveness endpoints. The trial enrolled 630 patients at 13 U.S. sites to evaluate the safety and efficacy of the synthetic hydrogel vascular closure technology designed to seal femoral artery punctures after interventional and diagnostic endovascular procedures. Patients were randomized on a 2:1 basis to standard compression, considered to be the "gold standard" for vascular closure.

Mark Turco, MD, director of the Center for Cardiac and Vascular Research at Washington Adventist Hospital (Takoma Park, Maryland), principal investigator for the trial, said the study results demonstrated that the technology "provides improved hemostasis and ambulation times, with a safety profile non-inferior to standard compression, as per our study protocol." He said the times to hemostasis and ambulation were "very impressive" and thus support use of such a closure technology. "What is different about this novel technology is that it provides secure and rapid extravascular closure with no animal by-products and bioresorbs within one month," Turco added.

Fred Khosravi, president and CEO of AccessClosure, said: "The data that we are seeing today are consistent with data we've seen in our European clinical trials and we are excited to share the results." He said the successful completion of the study "serves as a platform for AccessClosure to complete its premarket approval (PMA) application and also to bring forward a new pipeline of products for access-site management."

Final PMA submission is expected early this fall.

The company said that worldwide, more than 12 million arterial punctures each year require closure and groin management following interventional or diagnostic endovascular procedures. However, broad acceptance of currently approved closure devices has been slow due to safety and efficacy concerns when compared to manual compression.

The Matrix VSG System seals femoral arterial puncture sites through the simultaneous injection of two synthetic fluid components into the tissue tract of the access site. Once the two fluids are delivered, they mix subcutaneously to form a hydrogel sealant over the site, around the artery and in the tissue tract. The fluids are comprised of fully synthetic and non-thrombogenic polyethylene-glycol, a biomaterial commonly used in medical devices and pharmaceutical products.

AccessClosure is privately held and venture-funded.

Also at TCT, MacroPore Biosurgery (San Diego) reported that adipose tissue-derived regenerative cells improved heart function following myocardial infarction (heart attack) in a large-animal preclinical safety study. This study, performed in swine, confirms previous preclinical work by MacroPore and others suggesting that the company's patented technology is safe and may be clinically useful in treating heart disease.

The goal of the study was to determine the safety of adipose tissue-derived regenerative cells delivered into coronary circulation without cell culture. The results were presented in a TCT poster. Intracoronary infusion of adipose tissue-derived regenerative cells 48 hours after infarction was found to be safe, with all 13 swine surviving to the six-month follow-up period. Additionally, the study demonstrated a statistically significant improvement in left ventricular ejection fraction (LVEF) at six-months post-infarction in the treated group over the control group, as measured by 2-D echocardiography. Similar trends were observed by measuring LVEF via cineangiography.

"We are encouraged by the findings from this preclinical study, which suggest that delivery of autologous, adipose tissue-derived, regenerative cells is safe and effective in preserving left ventricular systolic function," said John Fraser, vice president, research and technology, at MacroPore. "Despite the fact that this study was designed primarily to evaluate the safety of dose escalation in limited infarcts, we observed statistically significant improvements in heart function. Additional swine studies are underway to better understand and optimize dosing and efficacy in order to lay the foundation for clinical work."

Elsewhere at TCT:

Guidant (Indianapolis) disclosed plans to conduct a study designed to increase clinical understanding of vulnerable plaques – lipid-rich coronary lesions that suddenly rupture – that may cause most heart attacks. The study will include 700 acute coronary syndrome patients receiving stents in the U.S. and Europe.

The study, Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT), will use novel intravascular imaging technology from Volcano Therapeutics (Rancho Cordova, California), a privately held company focused on the development of products for the detection and treatment of atherosclerosis and vulnerable plaques, to collect data about characteristics of lesions not causing symptoms at the time of treatment. The study will correlate lesion characteristics, patient risk factors and biomarker measurements with subsequent heart attacks and other cardiac events, potentially paving the way for physicians to identify and treat at-risk patients before a heart attack occurs.

"Guidant is initiating the first prospective natural history study that will provide highly anticipated data to help further the search for evidence-based clinical assessment of patient risk," said principal investigator Gregg Stone, MD, professor of medicine at Columbia University Medical Center (New York).

"The PROSPECT study will collect critical new information about the role of vulnerable plaque in unexpected heart attacks and about the natural progression of coronary artery disease," said Beverly Lorell, MD, vice president, chief medical and technology officer at Guidant. "As a growing body of scientific knowledge about vulnerable plaque is built, physicians may one day be able to better predict and prevent heart attacks."

The cause of most heart attacks was once believed to be the gradual closing of arteries over time as plaque build-up slowly increased, restricting blood and oxygen flow to the heart. However, the vast majority of heart attacks are now believed to be triggered by the rupture of a lipid-rich vulnerable plaque hidden under the surface of the artery wall, causing blood to clot on the plaque and suddenly block the artery. For this reason, heart attacks often occur in apparently healthy people who were unaware they have this type of plaque buildup in the walls of their arteries. Volcano's technology uses intravascular ultrasound radio frequency signal components to characterize lesion composition and morphology.

Rubicon Medical (Salt Lake City) reported that the adverse event rate 30 days following the procedures involving 51 initial patients enrolled in its RULE-Carotid, Europe study of the Rubicon filter was 6.1%. The RULE-Carotid study involved the testing of the Rubicon filter, a distal embolic protection device, specifically in carotid arteries. The studies were performed by leading cardiologists at three hospitals in Germany, with Joachim Schofer, MD, co-founder of the Center of Cardiology and Vascular Intervention (Hamburg, Germany), serving as the principal investigator.

Rubicon Medical also announced updated results for the RULE-SVG, Europe clinical study. The major adverse cardiac (MACE) event rate 30 days following the procedures involving 44 initial patients enrolled in the RULE-SVG, Europe study of the Rubicon filter was 4.5%. "The Rubicon filter's performance has been impressive in both the RULE-SVG, Europe and RULE-Carotid, Europe clinical studies," said Richard Linder, president and CEO of Rubicon Medical. "Physicians who've used the device have commented that the unique constraint and remote actuating technology platform of the Rubicon filter allows for a combination of ease, safety and control."

The constraint and remote actuating technology (CARAT) platform allows the company to externally constrain the filter portion of the device on its guidewire and to deploy the filter without the use of a delivery catheter. As a result, the filter is designed with an ultra-low crossing profile, providing cardiologists and interventional radiologists with the ability to deliver the Rubicon Filter past many blockages in blood vessels not previously navigable with other embolic protection filter delivery systems.

Rubicon received approval for up to 60 patients in the RULE-Carotid, Europe clinical study and will continue to collect data on additional patients. The company plans to use the collected data to generate the necessary reports as part of the clinical study protocol and file for regulatory approval for marketing clearance for the filter and its use in carotid arteries in Europe. It is currently expected that CE mark clearance for use in carotid arteries will be obtained in 2004.

The Rubicon filter is designed for use in medical procedures downstream from a blockage in a blood vessel to allow the capture and removal of dislodged embolic material. It is a guidewire-based filter that is deployed without the use of a catheter, making it smaller and easier to navigate through blood vessels.

Heartlab (Westerly, Rhode Island), a designer and supplier of digital image and information networks for cardiology, reported at the meeting that its CardioNow web-based technology for DICOM study sharing was used during the TCT conference to connect sites broadcasting live cases from around the world with conference attendees in Washington.

This year, 25 sites from countries including France, Germany, Korea and the U.S. performed live cases that were simultaneously broadcast to conference attendees. Post-procedure, sites broadcasting live cases used Heartlab's CardioNow WebSend PC-based DICOM study sharing software to electronically transfer complete angiograms of studies performed at their locations to the Washington Convention Center, where they then could be reviewed in native DICOM format from Heartlab Encompass review stations at the Heartlab booth or via standard PCs with Internet access.

The technology enabled attendees to review, discuss and analyze complete cases they may have missed during concurrent live sessions.

Cordis Endovascular (Warren, New Jersey), a division of Cordis (Miami Lakes, Florida), reported at the meeting that a patient in Newport Beach, California was the first to enroll in the company's surveillance study of its carotid artery stenting system for treatment of patients with carotid artery disease at high-risk for adverse events from carotid endarterectomy. "Through this surveillance study we seek to corroborate findings of the landmark SAPPHIRE study, the only randomized clinical trial conducted to validate the potential of carotid artery stent placement in high surgical-risk patients," said Subbarao Myla, MD, medical director, cardiovascular research and vascular interventions, Hoag Memorial Hospital Presbyterian (Newport Beach, California). "We are proud to be the first center to enroll a patient in this study."

The launch of this study followed the approvable letter that Cordis received in August from the FDA for the Precise nitinol self-expanding stent, part of the Cordis Carotid System. The FDA will review separately the second generation embolic protection device, the Cordis Angioguard XP emboli capture guidewire system, the second component of the Cordis Carotid System, under a 510(k) process. The company said it is currently working closely with the FDA to fulfill requirements for final marketing approval of both the Precise and Angioguard.

The FDA granted permission to Cordis Endovascular to initiate a surveillance study that will provide ongoing data about the carotid stenting procedure. When fully implemented, the surveillance study will enroll 1,500 patients at 112 sites in the U.S. These centers are being selected based on criteria agreed upon by the FDA and will represent a cross section of physicians who will be performing the procedure.

Carotid stenting is intended as an alternative to CEA, the current gold standard surgical treatment for removing arterial plaque from the carotid artery.

As part of the surveillance study, the FDA also granted permission to Cordis Endovascular to launch its comprehensive training program for physicians and other relevant healthcare professionals called CASES (Cordis Carotid Artery Stenting Education System). This training will include didactic review, case observations and simulation training, and hands-on experience at one of the Regional Education Centers across the country.

"CASES was developed by multiple thoughtleaders in the industry and was reviewed by the FDA and the Centers for Medicaid & Medicare Services," said Dennis Donohoe, MD, vice president, clinical and regulatory affairs, Cordis Endovascular. "It is the most recent initiative in Cordis' legacy of providing health professionals with 'best-in-class' education and training to ensure patient safety and medical proficiency in performing this breakthrough procedure."

In addition to clinical outcomes, the surveillance study will serve to validate the CASES program.

Vascular Solutions (Minneapolis) reported the presentation of preliminary results of the DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) clinical study. Presentation of the data from the first 60 patients of the 78 patients enrolled to date in the study was made by Dr. Pedro Silva of Milan, Italy. The DEAR-MI clinical study is a randomized evaluation of the use of the company's Pronto extraction catheter for the removal of thrombus from patients presenting with ST elevated acute myocardial infarction who are admitted within 12 hours of symptom onset.

The Pronto extraction catheter consists of a rapid exchange catheter with an atraumatic distal tip and large extraction lumen that can be percutaneously inserted into an artery to remove soft thrombus. An included locking vacuum syringe allows for single-operator deployment. The device received CE mark approval in August 2003 and FDA 510(k) clearance in December 2003.

Silva said the preliminary results indicate that thrombus aspiration with the Pronto catheter before standard percutaneous coronary intervention in acute myocardial infarction (AMI) cases "is safe and easy to perform and improves myocardial reperfusion as measured by complete ST-segment resolution and improved myocardial blush." He said differences in ST-segment resolution (64.2% vs. 35.5%) and myocardial blush grade (78.6% vs. 38.5%) between the Pronto arm and the control arm were statistically significant, indicating "the substantial benefit of thrombus aspiration with the Pronto."

An additional benefit, he said, "is our increased utilization of direct stenting, a technique that we performed in 59% of the first 60 patients in the study and have increased in use as we have gained more experience with this device." A total of 200 patients are expected to be enrolled in the trial.

Edwards Lifesciences (Irvine, California) featured several interventional cardiovascular technologies at the meeting. In addition to a number of presentations on the latest developments in its percutaneous heart valve initiatives, the company featured its new LifeStent line of peripheral vascular stent technologies. More than a dozen presentations were delivered on the latest developments in percutaneous heart valve technologies and the promise of the technology.

Alain Cribier, MD, chief of cardiology at University Hospital (Rouen, France), presented data in several sessions regarding the Cribier-Edwards percutaneous heart valve, a proprietary balloon-expandable stent technology integrated with a percutaneously delivered tissue heart valve. Among Cribier's presentations was 12-month follow-up data from one case in the current European clinical trials. During his presentation, he introduced the patient involved in this case, an 84-year-old woman who traveled from Paris to thank the clinicians in attendance for developing the technologies that have helped save her life. "This patient was suffering from a number of serious health challenges, and was unlikely to have survived traditional heart valve surgery due to her severe condition," Cribier said. "We were pleased to be able to help this mother of 11 children live to share this important one-year anniversary of her procedure."

Edwards also featured its LifeStent NT Self-Expanding biliary stent system for the first time since obtaining FDA clearance. The stent's self-expanding, triple-helix design provides physicians with a highly flexible intraluminal scaffold with sufficient radial strength to address clinical needs in a challenging area of the anatomy, the company said.

Spectranetics (Colorado Springs, Colorado) said its products were used in two live-case sessions. The first featured a 2.3 mm-diameter CliRpath excimer laser catheter recently cleared by the FDA to treat a total occlusion in the popliteal artery of the leg. The blockage was successfully treated by Drs. Giancarlo Biamino and Dierk Schienert of Leipzig Heart Center (Leipzig, Germany).

The second live case featured a patient with chronic total occlusion (CTO) in the left anterior descending coronary artery that was successfully crossed using a Prima Laser Wire and a Quick-Cross support catheter. The female patient treated had triple-vessel disease, with the target lesion having previously failed crossing attempts with mechanical wires. Jaap Hamburger, MD, of Vancouver General Hospital in British Columbia, performed the crossing of the CTO, which was about 20 mm in length, in roughly 10 minutes.

Siemens Medical Solutions (Malvern, Pennsylvania) reported that a live broadcast was shown from the first U.S. installation site of the Somatom Sensation Cardiac 64 computed tomography (CT) system. Siemens was showcasing the Somatom Sensation Cardiac 64, along with other interventional cardiac technologies, to demonstrate the role of this technology in non-invasive imaging of the heart and blood vessels.

Siemens bills the Somatom Sensation Cardiac 64 as "the world's first 64-slice CT scanner particularly optimized for cardiac, thoracic and vascular imaging." With a standard gantry rotation speed of .33 second and a spatial resolution of .4 mm, the scanner is routinely able to visualize the smallest coronary artery. The Sensation Cardiac 64 enables an ECG-gated coverage of the entire chest in a 20 second breath-hold, enabling evaluation, in a single scan, of the most common causes of acute chest pain.

The Beaumont Heart Center (Royal Oak, Michigan) was planning to broadcast a live cardiac CT patient scan in conjunction with the more traditional live broadcasts of interventional procedures at the meeting venue. The Thorax Center at Erasmus University (Rotterdam, the Netherlands) also was to broadcast a live Cardiac CT patient scan using the Somatom Sensation 64.

The broadcasts were intended to give physicians first-hand experience of the technology in terms of early diagnosis and management of heart disease, and they represented the first live CT broadcasts in the history of the TCT scientific sessions, the company said.