CD&Ds

It's not exactly the "paper or plastic?" debate, but chosing to go with a mechanical or tissue valve replacement is a question that patients with mitral valve failure must ponder. Until recently the popular choice has been to go with mechanical valves, since the devices provide strength and durability.

But there are drawbacks to taking the artificial route the mechanical device makes a loud ticking noise and patients often must take anticoagulation medicines to prevent clotting. And the tissue valve replacement which usually comes from pigs route can be even less promising, because it is significantly weaker and can tear easily.

However, Edwards LifeSciences (Irvine, California) is hoping to add a new dimension to the debate with its newly FDA-approved Carpentier-Edwards Perimount Magna mitral heart valve.

The early September approval came three years after the tissue based-device was given the green light in the European market and is slated to be thrust into the U.S. market, where there are nearly 40,000 mitral valve replacements a year.

"Instead of using the pig tissue, we're using bovine pericardial tissue," Donald Bobo Jr., Edwards' vice president for heart valve therapy, told Cardiovascular Devices & Drugs. "The bovine tissue is stronger."

He said there are two main reasons why pig tissue valve replacements have become so contentious.

"The [problem] is that first, the tissue can calcify and close the valve," Bobo said. "Second, the leaflet tissue is pliable and is easier to tear. The bovine tissue is much stronger and can still calcify but it there aren't many occurrences of that happening. But we do have therapies to prevent calcification."

He added that the Carpentier-Edwards ThermaFix process is an anti-calcification technology that was developed to help mitigate tissue valve leaflet calcification, one of the primary causes of tissue valve deterioration.

The company said that the Perimount Magna valve is the first mitral tissue valve to feature an asymmetric shape that mimics the native mitral anatomy. This design advancement, which it termed "significant and unique," provides what it said is the lowest effective profile and lowest ventricular projection for any tissue mitral valve in the industry.

In addition, the replacement valve is designed specifically to optimize patient blood flow and facilitates placement above the patient's native valve opening, which may allow surgeons to implant a valve that is larger than other conventional tissue valves.

"The Perimount Magna mitral valve represents a significant advancement for patients needing mitral valve replacement. It extends the exceptional hemodynamic performance and durability of the Magna valve platform to a design that is unique and specific to the mitral valve," Bobo said. "When surgeons see the new Perimount Magna mitral valve, they immediately appreciate that its design offers an advanced and easily implantable option."

The Perimount Magna mitral valve was launched in Europe in September 2005. It incorporates features of the Carpentier-Edwards Perimount mitral valve, which the company says has demonstrated 16 years of durability.

"This valve provides patients and surgeons with an important option for mitral valve replacement," said A. Marc Gillinov, MD, staff cardiac surgeon at the Cleveland Clinic Heart and Vascular Institute, and a paid consultant to Edwards Lifesciences. "The features of the valve, including its asymmetric shape, low profile and expansive sewing cuff, are designed to provide ease of implantation in a difficult valve position, low ventricular projection and strong hemodynamic performance."

Analysts say the Magna Mitral could better position the company to help address new surgical valve competition from St. Jude Medical (St. Paul, Minnesota) and Sorin (Milan, Italy). Edwards cited St. Jude and its Biocor implant as a key competitor in the market. Physicians have said Biocor is an easier device to implant than previous mitral valves from Edwards, thus taking market share from the company.

Biotronik EchoCRT study gets under way

Millions of people with heart failure could ultimately benefit from life-saving cardiac resynchronization therapy (CRT) if a new trial just underway proves that it helps.

Up to 70% of the 5 million Americans with congestive heart failure those with narrow QRS are currently treated with medication only and the prognosis for these patients is rarely good. In a new study, EchoCRT (Echocardiography-guided Cardiac Resynchronization Therapy), investigators are trying to determine if these patients could benefit from CRT.

The first implantation of Biotronik's (Berlin/Lake Oswego, Oregon) Lumax CRT was performed in late August at Ohio State University Medical Center (Columbus), marking the beginning of the 1,250-patient trial.

EchoCRT is intended to demonstrate that optimal medical therapy plus CRT reduces all-cause mortality or first hospitalization for worsening heart failure in the study population compared to optimal medical therapy alone.

"Originally the trials to get CRT devices approved in the market in Europe and U.S. were based on patients with wide QRS with an electrocardiogram (ECG) anomaly that shows longer-than-normal ventricular activity. They represent only 30% of all subjects with chronic heart failure," Kevin Mitchell, Biotronik VP of clinical studies, told CD&D.

He added, "Years ago when CRT started, the studies were based on the idea that if you have mechanical synchrony you also have electrical. Now we know that there isn't a close correlation between electrical and mechanical defects."

Mitchell said it's the largest, prospective, randomized, double-blind, international, multicenter clinical trial of its kind, with 125 investigational centers worldwide, including sites in Australia, Canada, Israel, Europe and the U.S.

CRT is a treatment for heart failure patients experiencing conduction abnormalities and a lack of synchronization in the two ventricles. An implantable cardioverter-defibrillator (ICD) is surgically inserted to constantly monitor heart rate and rhythm. When it detects a rapid, life-threatening heart rhythm, the ICD delivers a large electrical impulse to the heart muscle to restore normal rhythm.

The EchoCRT study will randomize patients with heart failure, already receiving current standard pharmacological therapy, with a narrow QRS width (less than 130 ms) and echocardiographic evidence of left ventricular dyssynchrony.

"All of the patients enrolled will receive the device. Half will be programmed to CRT therapy on and the others will have it programmed off," Mitchell said.

The Lumax also includes Biotronik home monitoring. That data will be used in a pre-specified analysis to evaluate the frequency and duration of irregular heart rhythms. Patients will be followed for a mean duration of 24 months.

In recognition of its substantial clinical benefits, CRT is recommended in both the European Society of Cardiology guidelines and in the American College of Cardiology/American Heart Association guidelines for the diagnosis and treatment of chronic heart failure. But those guidelines have limited the application of CRT to patients with a QRS width of = 120 ms. EchoCRT will assess whether some of the remaining 70% of heart failure patients with "narrow QRS" could benefit from CRT therapy.

EchoCRT was designed under guidance from an executive steering committee of 11 academic specialists in electrophysiology, heart failure and echocardiography who considered earlier studies in developing the EchoCRT design.

"Chronic heart failure is associated with a poor prognosis with considerably shortened survival and repeated hospitalizations," said Frank Ruschitzka, MD, of the University of Z rich, executive committee co-chairman and international co-principal investigator of EchoCRT. "The vast majority of patients with heart failure present with a narrow QRS and do not currently receive CRT. The EchoCRT trial will test the hypothesis whether CRT improves outcomes in this large subset of heart failure patients."

DuraHeart recipient discharged after 15 days

>The first U.S. patient implanted with a DuraHeart Left Ventricular Assist System (LVAS) from Terumo Heart (Ann Arbor, Michigan) was discharged in late August from the University of Michigan Health System (Ann Arbor), 15 days after receiving the device.

The company says the hockey puck-sized DuraHeart LVAS uses a new type of magnetic levitation technology (Mag-Lev) designed to eliminate mechanical contact within the blood flow path thus minimizing the chance of mechanical failure.

"We are extremely pleased with the performance of the DuraHeart and the recovery of our patient to an excellent functional state to permit discharge. We look forward to expanding upon our early experience with the DuraHeart in the near future," said Francis Pagani, MD, PhD, national co-principal investigator for the U.S. pivotal trial of the DuraHeart LVAS.

Terumo said the patient, a 62-year-old man from Livonia, Michigan, has been suffering from heart failure for nearly 20 years. The goal of these devices is to return the patient back to a relatively normal lifestyle and to provide improved quality of life, it said.

Mark White, marketing manager for Terumo Heart, told CD&D that the Mag-Lev technology is the core benefit of the DuraHeart, as it prevents a lot of the problems associated with other systems in which the impeller is suspended through pressure distribution.

With those systems, he said that when the pump is starting up for the first time, the impeller is just sitting on the bottom of the blood chamber, which can scratch the chamber surface and potentially create a source for cells to start clotting. He added that outside forces can potentially move the impeller, causing flow variations and even some areas of stagnant blood flow.

"Theoretically, if a patient is doing something really active like playing tennis, it's not inconceivable that it could deflect to the point of touching the chamber wall," White said. "You're relying on hydraulic characteristics to keep the impeller constant and centered and that's difficult to do."

The DuraHeart system, on the other hand, is controlled using position sensors to measure where it is and keep the impeller centered in the blood chamber. He compared it to playing with magnets and watching an object quickly snap to the middle of a magnetic field.

"It's rigidly positioned in the center of that chamber, regardless of what happens on the outside it never drifts out of that position," White said. "That gives you very consistent flow patterns ... no stagnant-flow areas, there is never any contact with the chamber wall ... that's really the core benefit."

He said there have not been any problems with blood clots in any of the DuraHeart systems that have been removed from patients, whereas other systems tend to have clotting issues. The company's engineers believe the Mag-Lev technology is responsible for keeping the devices clot free.

News of the first U.S. patient to receive a DuraHeart LVAS came almost simultaneously with HeartWare (Framingham, Massachusetts/Sydney, Australia) reporting that the first U.S. patient has received its LVAS at Washington Hospital Center (Washington), marking the start of its U.S. trial. Similar to the DuraHeart, the impeller that spins inside the HeartWare LVAS pump is also suspended by magnetic forces. Although both pumps are much smaller than earlier generation devices, the HeartWare is actually small enough to fit directly adjacent to the heart in the pericardial space. Most other systems, including the DuraHeart, are implanted into a surgically-created pump pocket in the abdomen.

Other companies developing similar devices include Ventracor (Chatswood, Australia), Abiomed (Danvers, Massachusetts) and Thoratec (Pleasanton, California).

Earlier this year Terumo received the go-ahead from FDA to start its U.S. trial of DuraHeart as a bridge-to-transplant device (MDD, March 5, 2008). The company also reported a couple months ago that the Institutional Review Board of the University of Michigan Health System voted to move forward with the trial (MDD, June 30, 2008). The trial is expected to enroll 140 patients at up to 40 centers.

In addition to the hockey puck-sized pump, the DuraHeart consists of the following components: an inflow conduit (a small titanium tube connecting the pump to the heart); an outflow conduit comprised of Vaskuteck Gelweave that is sewn to the aorta; a small battery-powered controller that serves as the brain of system and is worn or carried by the patient; and the hospital console, which allows doctors and hospital staff to monitor and have a degree of control over the pump.

Earlier-generation left ventricular assist devices (LVADs) are prone to hemolysis, blood clots and mechanical failure, Terumo noted. The company said it has tried to overcome these problems by combining the Mag-Lev technology and a centrifugal pump. The device has been used in more than 70 patients in Europe with the longest ongoing support more than three years. The device is intended to provide cardiac support for patients awaiting transplant who are at risk of death due to end-stage left ventricular failure.

Eventually, the company would like to get a "permanent" indication for the DuraHeart, in addition to the bridge-to-transplant indication. White said a trial for that indication is planned, but has not started yet. He said the permanent LVAS use market is much bigger than the bridge-to-transplant market because there are only about 2,000 donor hearts available and the criteria to receive a new heart is rather strict.

Cordis wins partial victory in Voda appeal

Patent lawsuits continue to dot the landscape for makers of medical devices, and Cordis (Miami Lakes, Florida) is only one of a number of device firms embroiled in a number of such suits, the pace of which seems to be increasing. Cordis last month managed to win a partial reversal of a juried court case that awarded Jan Voda, MD, of Oklahoma City, Oklahoma, potentially multiple millions of dollar in damages for what he alleges is an infringement of his design for a catheter. However, a new precedent that was set after the conclusion of that initial trial gave the defendant enough room to blunt some of the effect of the suit.

Voda sued the company in 2003 over the company's XB catheter and won handily with the damages set at 7.5% of gross sales despite the fact that Cordis went to market with the first iteration of the XB before Voda filed a patent for his invention. The crucial change to the original XB was a change in the catheter to a slightly curved design that apparently failed to be curved enough to avoid infringement of a catheter described as "straight," among other things.

The suit alleged that Cordis willfully infringed on the physician's patent and prior to the end of the first trial, Voda expanded the jurisdiction of his suit to four other nations, Britain, Canada, France and Germany.

The Federal Circuit Court of Appeals for the Western District of Oklahoma ruled on Aug. 18 that the lower court's instructions to the jury regarding willfulness were erroneous. The notion of willfulness in this context was affected by a lawsuit involving computer hard drive maker Seagate Technologies (Scotts Valley, California). That suit, which was decided in August 2007, is said to have lowered the bar for defending allegations that a defendant willfully infringed on a patent. The first trial in Cordis v. Voda concluded before the Seagate trial had run its course, but the appeal came after the closure of the Seagate trial, hence the application of that standard for willfulness.

The Circuit Court overturned the jurisdiction claim based on the lack of a provision affirming such a claim in the Paris Convention for the Protection of Industrial Property of 1883. However, the Paris Treaty does not ban such a claim, either. Voda also lost a motion to slap an injunction on Cordis' distribution of the XB.

Software snag leads to AED recall

Physio-Control (Redmond, Washington), maker of external defibrillators, has been in the news quite a bit over the past year and a half, and is now drawing more ink because of a recent class I recall of 249 units of its LifePak CR Plus automated external defibrillators (AEDs). The company initiated the recall because the units were loaded with software written for its semi-automated AEDs.

According to the Sept. 11 statement, the company already had completed the recall of the affected units, which when activated would display a prompt to "press the shock button to deliver therapy," according to the statement. Physio-Control indicated that the shock button is covered on the automated units and as a consequence, "it is possible that therapy could be delayed or not delivered at all, possibly resulting in death."

The company notes that one complaint has surfaced in connection with one of the affected units and that as of Sept. 2, it "has notified all affected customers and shipped replacement devices at no charge." In the meantime, the company recommends that customers either remove the unit or "remove and discard the shock button cover" per instructions it has provided.

The firm's owner, Medtronic (Minneapolis), had attempted to spin off Physio-Control last year, but production problems halted the plan. Medtronic signed a consent decree with FDA earlier this year over quality problems at Physio-Control's plant in Redmond, but FDA's warning letter database indicates no issuance of a warning letter.

Ann Devine, public relations manager at Physio-Control, told CD&D that the problem with the incorrectly downloaded software was due to a "keying-in error." She also said that the hardware design of the LifePak CR fully automated unit is essentially the same as the semi-automated unit for which the software in question was written, hence the availability of the shock button on the automated version.

Regarding the company's persistent problems with regulations governing good manufacturing practices, Devine said, "We're working very closely with FDA and with a third-party auditor" to bring operations into compliance. She said the company and FDA have not yet set up a future inspection date to check on the company's corrections.

New guidance for ultrasound 510(k)s

FDA has published a new guidance for those "seeking marketing clearance of diagnostic ultrasound systems and transducers."

The 68-page guidance covers intravascular ultrasound catheters and cardiovascular blood flow meters as well as ultrasonic pulsed Doppler imaging systems. One thing has not changed, the guidance notes, informing the reader that the guidance "retains the two-track approach of the 1997 guidance." Track 1 recommendations "are for devices that do not conform to the output display standard," whereas those for track 3 deal with devices that do conform to that standard.