CD&Ds

ATS Medical (Minneapolis), a maker of cardiac surgery products, said last month that it had completed the final feasibility milestone in the development of its Forcefield technology, a process designed to control the initial interaction between blood and an artificial device, such as a mechanical heart valve prostheses.

"Normally, any device upon insertion into the bloodstream will be recognized as foreign and the body's initial reaction is to send signals that say, 'Hey folks, this isn't supposed to be here'," Michael Dale, president/CEO of ATS, told Cardiovascular Devices & Drugs. What happens next is the activation of platelets, which he explained as the "proverbial bouncers at a bar" which inhibit the device, a reaction that often leads to thrombosis, or clotting.

ATS says its 90-day animal feasibility study was completed with positive results regarding the inhibition of platelet adhesion on mechanical heart valve prostheses. But the fact that the technology worked isn't what makes this animal study significant, Dale said, because the company had already proved the efficacy of Forcefield in earlier acute human clinical studies.

"We needed basic evidence of sustainability of this effect," Dale said. "This provides the green light to go forward and plan for human clinical studies."

ATS said its Forcefield technology has been the focus of presentations at the American Society for Artificial Internal Organs (Boca Raton, Florida) conference in June and at the European Association for Cardio-Thoracic Surgeons meeting in September. Previously,

Mark Slaughter, MD, professor and chief of cardiothoracic surgery at the University of Louisville and Jewish Hospital (both Louisville, Kentucky), presented his findings in an acute human trial with "excellent results," according to ATS.

The company said its 90-day animal feasibility study has demonstrated the longer-term sustained effect of Forcefield on a functioning mechanical heart valve implanted in the mitral position. Examination of the surviving animals confirmed essentially zero presence of platelets on the surface of the heart valves after 90 days without the use of anti-coagulation treatment, ATS noted.

"This is a big deal, this has never been demonstrated before with any device or technology," Dale told CD&D.

Even more significant is what this technology could potentially mean for future patients who receive an implanted device with Forcefield – the elimination of anti-coagulation therapy. Dale said the company's next step would be to plan for human feasibility trials of the technology.

"Forcefield is an enabling technology insofar as the biocompatible interface that we create between a device and the bloodstream is the result of controlling the manner by which a person's blood first interacts with a device," Dale said. "The result is a natural solution and genuinely biocompatible interface between the device and bloodstream."

He added, "The magnitude of this achievement is one of a kind and we predict will be disruptive in the future to the implantable device marketplace. The elimination of long-term anti-coagulation medication would provide physicians greater therapy options in the selection of device type and most importantly better therapy for their patients."

The company's initial product is its Open Pivot Heart Valve, which the company says continues to spur growth in the mechanical valve market segment. Its other offerings include Simulus annuloplasty products for heart valve repair and CryoMaze surgical ablation products.

MIT develops scaffold to mend broken hearts

Researchers at the Massachusetts Institute of Technology (MIT; Cambridge, Massachusetts) have developed a new accordion-like honeycomb scaffold that they say may one day be used to repair, well, broken hearts.

The MIT team believes that living heart cells or stem cells seeded onto such a scaffold would develop into a patch of heart tissue that could be used to treat congenital heart defects or to help repair tissue damaged by a heart attack. The biodegradable device would be gradually absorbed into the body, leaving behind new tissue, the researchers say.

The scaffold, reported in the Nov. 2 online edition of Nature Materials, is designed to more closely match the structural and mechanical properties of native heart tissue than traditional scaffolds, according to George Engelmayr Jr., lead author of the paper and a postdoctoral fellow in the Harvard-MIT Division of Health Sciences and Technology (HST).

Engelmayr told CD&D that traditional "off-the-shelf" scaffolds have basically been adapted for myocardial repair but not specifically designed for this application. He said such scaffolds have been structurally incompatible with recapturing cardiac anisotropy. Heart tissue has to be flexible enough to change shape as the heart contracts, but strong enough to withstand the forces generated by the contractions.

The objective of Engelmayr's team's research was to create a scaffold designed explicitly for hearts, unlike current scaffolds, which are made out of synthetic materials.

The MIT team seeded small patches of the scaffold with heart cells from newborn rats and grew them for one week. They found that the mechanical and electrical properties of the engineered tissue varied in different directions. When the cells were lined up parallel to an electric field, for instance, they beat in sync more readily.

Engelmayr and his colleagues used microfabrication techniques to create the accordion-like honeycomb microstructure in poly(glycerol sebacate), which yields porous, elastomeric 3-D scaffolds with controllable stiffness and anisotropy.

The accordion-like honeycomb scaffold has three key advantages over traditional cardiac tissue engineered scaffolds, Engelmayr said: First, its mechanical properties closely match those of native heart tissue. For example, it is stiffer when stretched circumferentially as compared to longitudinally. Surprisingly though, the new scaffold "turned out to be a better match for the right ventricle rather than the left ventricle," Engelmayr told CD&D.

Engelmayr found that he could essentially "dial in" specific mechanical properties for the polymer scaffold by varying the time it is allowed to set, or cure. He noted that with this ability, coupled with the flexibility of the laser technique, "we might be able to come up with even better pore shapes with better mechanical properties."

Second, the MIT team demonstrated heart cell contractility inducible by electric field stimulation with directionally dependent electrical excitation thresholds. Heart muscle, Engelmayr explained, is directionally dependent – meaning its cells are aligned in specific directions. Third, his team saw greater heart cell alignment on the accordion-like honeycomb scaffolds than isotropic control scaffolds.

"Prototype bilaminar scaffolds with 3-D interconnected pore networks yielded electrically excitable grafts with multi-layered neonatal rat heart cells," the MIT researchers noted. "Accordion-like honeycombs can thus overcome principal structural–mechanical limitations of previous scaffolds, promoting the formation of grafts with aligned heart cells and mechanical properties more closely resembling native myocardium."

The National Institutes of Health, National Aeronautics and Space Administration, and Draper Laboratory sponsored the research.

"At this point we have not done any in vivo studies yet, but this is certainly on the horizon," Engelmayr said.

Medtronic pushes ahead with RX sales

As quickly as a patent and a related court injunction expires, another lawsuit is filed in the ongoing case of Abbott's (Abbott Park, Illinois) patent for a stent delivery system. It has sought to prevent Medtronic's (Minneapolis) access to the system for eight years.

But the day after the injunction was lifted early last month, Medtronic launched its portfolio of angioplasty products in the U.S. on the Rapid Exchange (RX) Delivery System, including the Endeavor drug-eluting stent (DES), the Driver and MicroDriver bare-metal stents, and the NC (non-compliant) Sprinter balloon catheter systems.

A day later, Abbott filed suit in the U.S. District Court for the Northern District of California asking for a new injunction, Medtronic spokesman Joe McGrath told CD&D.

At the heart of the intellectual property war is the RX delivery system, popular among physicians because it enables a single operator to deliver angioplasty products, including balloon catheters and stents, through the coronary vasculature. As a short-, single-wire system, it is an alternative to the over-the-wire (OTW) delivery system, a dual-, long-wire system that requires two operators.

"We expect RX to add about two to three share points in the U.S. for the Endeavor drug-eluting stent," McGrath said. "With access to RX, we expect Endeavor's U.S. market share to stabilize in the high teens."

Medtronic said it has abided by the injunction since it was originally issued in 2000 for any RX catheter which infringes claim three of what's now known as the '233 patent.

"RX is the delivery system preferred by three-quarters of U.S. interventional cardiologists," McGrath said. "Medtronic's angioplasty products have previously been available on the OTW delivery system and our proprietary Multi-Exchange (MX) 2 delivery system, a short-, single-wire system. They remain available on these delivery systems."

"RX is a prescription for greater success in cardiac catheterization laboratories nationwide going forward," said Sean Salmon, VP and general manager of the Coronary and Peripheral Vascular business at Medtronic. "Delivering the Endeavor stent on RX makes our flagship DES even more deliverable."

E added, "Given the popularity of RX among physicians, patients with coronary artery disease across the country will soon be much more likely to receive the Endeavor stent, which has demonstrated both long-term safety and durable efficacy in extensive clinical research."

McGrath pointed out that the addition of RX adds no cost to Medtronic's products. "We've been manufacturing the Endeavor stent on RX in Ireland for several years for sale in international markets outside the U.S.," he said.

Medtronic received the CE mark for its Endeavor drug-eluting coronary stent with RX delivery system in 2005.

Thoratec shares waver after HeartMate II deaths

Thoratec (Pleasanton, Caifornia) shares took as much as a 20% trouncing in late October after the company reported that it had issued a notice to hospitals following 27 reports concerning wear and tear to its HeartMate II Left Ventricular Assist System (LVAD) for end-stage heart failure.

According to the company, wear and tear to the percutaneous lead connecting the HeartMate blood pump with the system controller can interrupt pump function, and in the reported cases lead to the need for pump replacement. Thus, Thoratec issued an Urgent Medical Device Correction notice. In five cases replacement wasn't an option and those patients died.

That notice went out to hospitals and identified the probability and symptoms of the problem, and recommended that the pump be replaced as soon as possible if damage to the percutaneous lead is confirmed. Hospitals were also requested to review the instructions for care of the percutaneous lead with their ongoing HeartMate II LVAS patients.

The company held a conference call yesterday to discuss concerns from the Friday announcement and to possibly put out any fires.

"This notice was a safety advisory only – and I want to be clear about what this correction notice does not involve," President/CEO Gerhard Burbach said during the conference call. "First there's no impact on product shipement activities and we're continuing to provide Heartmate IIs to customers. We're not asking for the devices to be returned; there's no underlying manufacturing defects and we don't expect to experience any material financial impact."

These reports occurred throughout five years of clinical experience with 1,972 implants. All patients who have undergone a replacement of the HeartMate II pump survived the operation and were alive at least 30 days postoperatively. The affected systems were distributed to 153 hospitals and distributors throughout the United States, Europe, Canada and other countries.

The device was given FDA approval in April.

Questions concerning the mode of failure in LVD's popped up during the conference call. A caller pointed out that pulsatile pumps have had a mode of failure for LVD since the 1980s and that this recent release isn't anything new in the clinical setting.

"I guess the fundamental question to start with is why are we seeing this press release now," the caller asked. "Why the necessity for it and what does it suggest for the durability of the Heart Mate II?"

Burbach responded saying that he wanted to have as much "open communication" and "transparency" as possible and the device would still be offered to customers.

Thoratec declined to provide any details about the patients who died or their use of the heart pump. The device includes an electrical cable to power the blood pump which passes through the patient's skin to an external controller that the patient wears on his or her waist. The controller is powered either by batteries or connected to an electrical power outlet. Blood flow is set through the pump based on the patient's need, and the controller monitors pump performance, sounding alarms if it detects dangerous conditions or a possible malfunction.

The system can operate on two external batteries, allowing the patient to move freely for up to three hours.

FDA approves carotid artery stent

Cardiovascular surgeons in the U.S. have a new carotid artery stent in their toolbox when treating patients with carotid artery disease – a device their counterparts in Europe have had at their disposal since 1999.

The FDA in late October approved Boston Scientific's (Natick, Massachusetts) Carotid Wallstent Monorail Endoprosthesis for patients with carotid artery disease who are at high risk for surgery. The Wallstent is the "leading carotid stent" in Europe and other international markets, according to the company. It is a self-expanding stent mounted on a rapid exchange delivery system, designed to re-open the carotid artery by treating stenosis, and improve blood flow to the brain.

"It's a highly deliverable system, it allows the physician to place the device in very tortuous anatomy, [and] it's a low-profile design," Scott Warren, group marketing manager of Carotid Solutions at Boston Scientific, told CD&D.

Warren said there are three key differences between the Wallstent and competing devices: first, the Wallstent has the smallest free-cell area because it features a closed-cell stent design; second, it has the "unique ability to be re-constrained," he said, which allows the physician during the deployment of the device to stop, re-constrain and re-deploy the device if necessary to achieve better placement of the stent; and third, the Wallstent is the only carotid artery stent system approved in the U.S. with an indication for bilateral carotid artery disease, meaning blockages in the carotid arteries on both sides of the neck.