Another company has taken a step toward U.S. approval for a ventricular assist device (VAD), reporting FDA approval for its pivotal trial. Jarvik Heart (New York) the company whose namesake, Robert Jarvik, MD, invented the original artificial heart implanted in Barney Clark more than 20 years ago said in mid-July that it had received full approval from the FDA to begin a pivotal trial of the Jarvik 2000 FlowMaker, for bridge-to-transplant use, with an eye toward ultimate approval of the device as a destination therapy.

The pivotal study is designed to establish the safety and efficacy of the Jarvik 2000 in supporting severe heart failure patients while they await the availability of a donor heart for transplant. In Europe, the Jarvik 2000 has earned the CE mark for both bridge-to-transplant and destination therapy, and has been supporting its first lifetime-use patient for more than five years with what the company called "an excellent quality of life."

Jarvik Heart said it plans to submit an application to the FDA later this year for a pivotal study of the Jarvik 2000 for use as a destination therapy in the U.S. under a protocol designed for the treatment of heart failure in earlier-stage patients. The company said that using the mechanical heart earlier before patients suffer too much damage to other organs is expected to help them recover more rapidly to a normal life. According to Jarvik, while a bridge-to-transplant approval may help some patients, that clearance is merely a stepping-stone toward the more important use for a VAD. "The thing that is needed in a public health sense is a long-term, heart-assist device that is really simple and [provides] a good quality of life for people," he told Cardiovascular Device Update.

Jarvik said that his company's emphasis is different from the majority of other players in this sector. "We're trying to introduce treatment for the sake of relieving the symptoms of severe heart failure. Most efforts have been solely toward extending life" after patients had already reached a critical stage where the device is largely a last-minute rescue device. He said VADs "should be used earlier for lifetime use or for very long-term bridge-to-transplant type of use that we have named maintenance therapy."

Up to 160 patients will be enrolled in the pivotal study at 25 medical centers throughout the U.S. At the time of its announcement, the company reported nine "trained" implant centers, saying that 16 additional implant teams will be added over the next year. In addition to the survival rate to transplant, the study will examine patient quality of life and rates of serious adverse events, the company said.

The launch of the pivotal study follows completion of a pilot study of the Jarvik 2000 in the U.S., which enrolled 63 patients at eight medical centers. Many of those patients are surviving up to five years following implant of the mechanical heart and subsequent transplant.

Elsewhere in the product pipeline:

Biotronik (Lake Oswego, Oregon) reported last month that it has received FDA approval to market its Protos CLS family of single-chamber and dual-chamber pacemakers as responding to physiologic dem-ands instigated by exercise and acute mental stress, a claim that serves to differentiate its systems from other companies selling the devices in the U.S. Technology embedded in the privately held company's pacemakers, called Closed Loop Stimulation (CLS), is designed to integrate with the natural control centers of the heart to provide a physiologic and appropriate heart rate. Biotronik originally received approval to market its Protos DR and VR pacemakers from the FDA in late-December 2002 but this newest approval allows the company to make marketing claims that its pacemakers can respond to varying levels of stress, more closely mimicking the true functions of the human heart. Traditionally, rate-adaptive pacemakers sense that patients are in motion or that they have changed their respiration rate in order to increase or decrease heart rates. Protos with CLS measures contraction dynamics in the right ventricle, thereby integrating the heart rate back into the cardiovascular control loop. In such cases, rate adaptation is accomplished by interpreting what the autonomic nervous system really needs in situations involving exercise and other demands, and then adjusts automatically to avert any possible over-response or under-response. This capability, said the company, allows for long-term reliability and optimization, regardless of changes in a patient's heart condition. Biotronik also reported FDA approval of the ICS 3000. The programmer features a 12-inch high-resolution, high-contrast, lightweight LCD touch-screen color display; jam-resistant thermal printer; CD-RW drive; USB ports; and 30 gb hard drive. The ICS 3000 also incorporates a detachable screen to simplify and improve follow-up efficiency, essentially transforming the programmer into a tablet PC, the company said. The ICS 3000 will be made available to U.S. hospitals and clinics that implant Biotronik cardiac pacemakers and im-plantable cardioverter defibrillators.

Two patients in Brazil in late June became the first patients outside the U.S. to receive a paclitaxel-coated stent to treat peripheral arterial disease (PAD). The two men were released from Casa de Saude Sao Jose Hospital the day after they received Zilver PTX drug-eluting vascular stents from Cook (Bloomington, Indiana) as part of a worldwide trial to determine whether drug-eluting stents (DESs) are as effective in treating PAD as they are in treating heart disease. Cook's Zilver PTX Drug-Eluting Vascular Stent is under investigation for the use in the treatment of symptomatic vascular disease of the above-the-knee femoropopliteal artery. The Zilver PTX trial is being conducted initially in 31 U.S. medical facilities and will enroll 60 patients. In May, Cook expanded its trial to include up to 760 patients at more than 50 sites in Europe, Asia, Australia, Canada and Latin America. The study compares the safety and effectiveness of the drug-eluting stent to standard PAD interventions, and is the first trial to test if a paclitaxel-eluting DES device can be used to treat PAD, Cook said. Cook holds a co-exclusive license from Angiotech Pharmaceuticals (Vancouver, British Columbia) for the use of paclitaxel in the peripheral vascular and also for gastrointestinal use.

Cytori Therapeutics (San Diego), which is developing cell-based therapeutics using adult stem cells, reported preclinical findings that demonstrate that adipose-derived stem cells (ADCs) will engraft in injured heart muscle following a heart attack-like injury. Adipose, also known as fat tissue, contains a specialized class of stem cells, which are comprised of multiple cell types that may promote healing and repair. The results are reported in the July issue of Cytotherapy. The study, which evaluated three groups of 12 mice, suggests that ADCs home in on specific sites of injury through biological signaling that occurs naturally during heart attacks, the company said. Additionally, it was observed that the areas immediately surrounding the infarct regions express markers of endothelial cells, suggesting the ADCs may participate in inducing blood vessel growth or repair.

Dade Behring (Deerfield, Illinois) said that its Dimension Vista 1500 integrated system, which will be its first integrated chemistry/immunochemistry system targeted at high-volume clinical laboratory customers, has received 510 clearance from the FDA. This is the first of a series of submissions and ap-provals prior to the anticipated commercialization of the Dimension Vista system in the second half of 2006. The Dimension Vista 1500 integrated system will combine photometry, turbidemetry, nephelometry, integrated multisensor technology and LOCI technologies. The new design will integrate analysis of electrolytes, general and special chemistries, drugs-of-abuse, therapeutic drugs, immunosuppressive drugs, plasma proteins, cardiac marker tests and high-sensitivity immunoassays into one analyzer.

Guidant (Indianapolis) last month reported on two of its trials, one for surgical ablation of cardiac tissue and the other for its emerging drug-eluting stent program. The company reported the enrollment of the first patient in a clinical trial designed to study a new therapy for the treatment of permanent atrial fibrillation (AF). The trial will evaluate the safety and efficacy of the Flex microwave surgical ablation system to treat permanent AF patients undergoing mitral valve surgery. Results of the trial may be used to obtain FDA approval to treat permanent AF with the technology, the company said. The first patient was enrolled in the trial in late June by John Johnkoski, MD, cardiothoracic surgeon, at Wausau Hospital (Wausau, Wisconsin). Called RESOLVE-AF (RandomizEd Study Of SurgicaL Ablation with MicrowaVe Energy for the Treatment of Atrial Fibrillation), this prospective, randomized trial will enroll 200 patients at up to 40 U.S. and European centers. Guidant's Flex system, which includes a surgical ablation probe and microwave generator, directs microwave energy to targeted tissue to induce cell death. The system typically is used to ablate heart tissue during a coronary artery bypass surgery or mitral valve surgery, but also can be used in minimally invasive, closed-chest procedures. Guidant acquired the Flex technology via its acquisition of AFx (Fremont, California) in February 2004. The system has been used in more than 8,000 procedures worldwide. In March, the device received the CE mark specifically for the treatment of AF, in addition to other cardiac ablation uses. The company is pursuing individual ablation clearances, including the important AF market. Guidant also reported that it has begun enrollment in its SPIRIT II drug-eluting stent clinical study. SPIRIT II is a 300-patient study evaluating the Xience V, an everolimus-eluting coronary stent system using the company's cobalt chromium Multi-Link Vision coronary stent system platform. This single-blind, randomized controlled study further evaluates the Xience V compared to Boston Scientific's Taxus Express2 paclitaxel-eluting coronary stent system for the treatment of coronary artery disease. Results of the SPIRIT II study will provide additional clinical data to support the launch of Xience V in several countries outside the U.S. the company said. The first patient was enrolled by Gert Richardt, MD, of Segeberger Kliniken (Bad Segeberg, Germany). "I am enthusiastic about the potential of the Xience V everolimus-eluting stent system for the treatment of coronary artery disease," Richardt said in a statement. Guidant disclosed in June the U.S. initiation of SPIRIT III, a large-scale pivotal clinical trial evaluating Xience V, a study which may be used to obtain FDA approval for the system for the treatment of coronary artery disease.

Medtronic (Minneapolis) reported the U.S. introduction of the EnTrust implantable cardioverter-defibrillator (ICD). The company said the EnTrust single- and dual-chamber devices expand its premium line of ICDs, which are designed to treat patients with ventricular tachycardia (VT) that can lead to sudden cardiac arrest. The EnTrust ICD family was approved by the FDA on June 14. EnTrust is the first ICD to offer ATP During Charging, a Medtronic-exclusive feature that automatically uses pacing pulses to painlessly stop fast, dangerous heartbeats, while concurrently preparing to deliver a shock if needed. The company said recent clinical studies have shown that 90% of fast heart rhythms have the potential to be terminated by pacing alone. It said the use of this anti-tachycardia pacing to stop fast heartbeats has been clinically proven to eliminate three out of four shocks with painless therapy, potentially improving patient quality of life. The EnTrust dual-chamber ICD also helps reduce inappropriate therapy by better identifying episodes of supraventricular tachycardia, which may ensure that patients receive appropriate shocks. The dual-chamber version also incorporates a pacing mode called Managed Ventricular Pacing (MVP), which promotes natural heart activity by "significantly reducing" unnecessary pacing in the heart's ventricle. This algorithm can reduce the amount of ventricular pacing to a median of 0.1%, compared to 50% or more with typical dual-chamber ICDs, Medtronic said. MVP has been available in several of its pacemakers and defibrillators since 2004.

MIV Therapeutics (MIVT; Vancouver, British Columbia), a developer of biocompatible stent coatings and drug delivery technologies, said it has completed Phase I animal feasibility studies in sheep of two models of an implantable arterial filtration technology device designed to prevent strokes by diverting embolic particles flowing through the bloodstream. These two models of MIVT's Aortic Embolic Protection Device (AEPD) are designed to prevent both major types of embolic strokes those triggered by heart surgery and catheterization, and those that occur naturally, not in connection with such procedures. The AEPD filtration devices are being developed by wholly-owned MIVT subsidiary SagaX Medical Technologies (Herzliya, Israel). Both AEPD filter prototypes use stent-based filter-deflector technology. The AEPD I prototype model is designed to be implanted temporarily in the aorta during heart surgery and heart catheterization to divert particles that might otherwise reach the brain, where they could trigger embolic strokes. The AEPD II prototype is designed to be implanted permanently to prevent the embolic strokes that occur from natural causes, such as aging. The studies are being conducted at the Hadassah University Hospital (Jerusalem) Cardiology Research Institute .

Novadaq Technologies (Toronto), which is developing medical devices based on its imaging platform for the diagnosis and treatment of vascular and ophthalmic conditions, said that it has been granted a patent by the U.S. Patent and Trademark Office for the SPY Intra-operative Imaging System. The FDA-cleared SPY System enables real-time visual confirmation of revascularization during heart bypass surgery, which the company said allows bypass graft technical errors to be detected and corrected while the patient is still in the operating room. U.S. patent No. 6,915,154 B1, "Method and apparatus for performing intra-operative angiography," describes the SPY intra-operative fluorescent imaging system that enables cardiac surgeons to confirm the location of coronary arteries during coronary artery bypass graft procedures and visually assess and validate the functionality of bypass grafts.