A study released last month by Frost & Sullivan (London) indicates that the Eastern European cardiac rhythm management (CRM) devices market is expanding slowly. The report, Eastern European CRM Devices Market, says that accession by Eastern European nations to the European Union (EU), coupled with greater awareness of arrhythmia, is boosting market prospects. However, consolidation at the global level, pricing pressures and technological concerns continue to pose challenges to market growth, according to the global consulting firm.

The study says that the market had revenues of $50.5 million in 2006, expected to reach $75.5 million by 2013. “Demand for CRM devices is rising due to the increased incidence of arrhythmia,” said F&S Research Analyst Sowmya Rajagopalan. “At the same time, manufacturer-driven trainings, workshops and symposiums are boosting awareness of the disease and its available treatments, providing a fillip to the uptake of CRM devices in the region.”

The report says, however, that technical constraints could dampen market growth. “CRM devices act as life-saving devices for a specified period depending upon the lifespan of the battery,” the report said. “Currently, these batteries have a short life cycle, thus increasing the need for repeat implantations. Due to their technological sophistication, these products are highly priced. As a result, such repeat procedures aggravate already burgeoning healthcare expenditures.”

Rajagopalan added: “The mounting pressure to reduce prices and gain market share presents another challenge. [And] reimbursement rules that aim to curb spiraling healthcare expenditure, have effected reduced funding allocations for these implantations.”

UK study cites role of MPO in testing of cardiac risk

A study published in the July 10 issue of the Journal of the American College of Cardiology (JACC) reports that European researchers have uncovered a new clue to the mystery of how a seemingly healthy person can actually be at high risk for heart disease or a heart attack. The culprit is myeloperoxidase (MPO), a protein secreted by white blood cells that signals inflammation and also releases a bleach-like substance that damages the cardiovascular system. Although MPO is intended to kill harmful bacteria, it may instead inflame the arteries and cripple protective substances in the blood, according to the study. Long before conventional risk factors set off alarms, elevated MPO levels signal the build-up of harmful plaque.

“We were surprised to find that many years before a cardiovascular event actually occurs, MPO is increased,” said Matthijs Boekholdt, MD, PhD, a resident in cardiology at Academic Medical Center (Amsterdam, the Netherlands). “As we learn more about these processes, we hope to be able to identify ‘vulnerable blood’ as a reliable tool for detecting vulnerable patients.”

Boekholdt and colleagues recruited healthy people living in Norfolk, UK, between 1993 and 1997, as part of a larger community-based research program known as the European Prospective Investigation Into Cancer and Nutrition (EPIC). They took baseline blood samples from each participant and froze the samples for future analysis.

After an average of eight years, 1,138 EPIC-Norfolk participants had been admitted to the hospital or died from the effects of coronary artery disease (CAD), including heart attack. The average blood levels of MPO were “significantly higher” in those who developed heart disease than in those who remained healthy. When MPO levels were divided into four groups, patients in the highest fourth were 1.49 times as likely as those in the lowest fourth to develop CAD or have a heart attack.

When traditional risk factors blood pressure, LDL and HDL cholesterol levels, body mass index, smoking and diabetes were taken into account, an MPO level in the highest fourth increased the risk of heart disease by 1.36 times. Elevated MPO levels signaled increased risk even in those with acceptable levels of LDL cholesterol, HDL cholesterol or C-reactive protein, a well-known marker of inflammation.

One of the study’s authors, Stanley Hazen, MD, PhD, is named as a co-inventor on pending patents filed by the Cleveland Clinic Foundation (Cleveland, Ohio) relating to the use of MPO as a biomarker for cardiovascular disease.

Volcano wins Japan approval of s5i Integrated IVUS System

Volcano (Rancho Cordova, California) reported approval of its s5i Integrated IVUS (intravascular ultrasound) System by regulatory authorities in Japan.

Volcano said it expects to launch the s5i into Japan — which it says represents the largest IVUS market worldwide — this quarter. The company noted that it has already launched the s5i Integrated IVUS system into the U.S. and Europe.

Volcano said the s5i is its first IVUS system that can be integrated into new or existing cath labs. The company said it can now tailor an integrated IVUS solution to the unique user and workflow needs for virtually any vendor’s cath lab type or configuration, including multiple controllers and monitors, as well as flexibility in the physical location of the console. The s5i also incorporates Volcano’s real time VH IVUS tissue characterization functionality that enhances the interpretation of IVUS images, and ChromaFlo Stent Apposition analysis which helps physicians confirm proper stent expansion and placement.

Volcano said the s5i IVUS is the only IVUS system to have undergone extensive safety and compatibility testing with Innova series from GE and the Axiom from Siemens. Artis FD series), Philips (Allura series), and Toshiba (Inifinix-I series).

Scott Huennekens, president/CEO of Volcano, said the approval “makes Volcano the only company to offer an integrated IVUS console to the largest worldwide IVUS market ... and believe that the lessons learned through IVUS by Japanese physicians will help increase the use of IVUS in the U.S. and Europe as well.”

Ron Waxman, MD at the Washington Hospital Center, said, “We recently performed an analysis of 7,000 patients at our center and concluded that the incorporation of IVUS guidance into everyday PCI procedures can reduce the patient risk of stent thrombosis by a statistically significant margin. We have always been IVUS advocates, but these new findings have driven IVUS use at the Hospital Center to its highest level ever.

Abiomed reports approval, 1^st use of Impella tech in Canada

Abiomed (Danvers, Massachusetts) reported that its Impella 2.5 and Impella 5.0 circulatory support products have been approved for use in Canada by Health Canada’s Therapeutic Products Program. The company said that the first Canadian patients have received treatment with the Impella 2.5 at the Peter Munk Cardiac Center at Toronto General Hospital.

“We look forward to working with Canadian cardiologists and surgeons to improve clinical outcomes for patients,” said Michael Minogue, president/CEO and chairman of Abiomed.

Vladimir Dzavik, MD, director of the cardiac cath lab and interventional cardiology at the Peter Munk Cardiac Center, said, “We are [pleased] to be the first hospital in Canada to use this exciting new catheter-based circulatory support technology for heart failure patients. We expect the Impella devices to be key treatment options for clinicians in our cath lab and surgical suites.”

The Impella 2.5 is a ventricular-assist catheter inserted percutaneously in the cath lab via the femoral artery into the left ventricle. Up to 2.5 liters of blood per minute are delivered by the pump from the left ventricle into the ascending aorta, providing the heart with active support in critical situations.

Abiomed noted that the Impella 2.5 can be inserted quickly and provides cardiovascular support for a high-risk patient population while having such percutaneous coronary intervention as a stent or balloon angioplasty. The device also can be used to provide additional blood flow to patients with low cardiac output, such as post-cardiotomy, or to protect the muscle of the heart following a heart attack.

The product also is available in Europe, and Abiomed recently reported that it has completed enrollment for the pilot study of the Impella 2.5 in the U.S.

Abiomed’s Impella 5.0 technology consists of catheters that can be introduced percutaneously through a cut-down or surgically. The company said these pumps can achieve flows of up to 5.0 liters per minute, and actively unload the ventricle, reducing myocardial workload and oxygen consumption while increasing cardiac output and coronary and end-organ perfusion.

The Impella 5.0 support systems are intended to be used for up to seven days as left ventricular cardiac-assist devices. They are currently available in Europe and are in pilot studies in the U.S. under an Investigational Device Exemption.

Medtronic’s Reveal XT device introduced for AF monitoring

Medtronic (Minneapolis) reported the European introduction of Reveal XT, which it described as “the first insertable cardiac monitor that offers long-term and continuous monitoring of atrial fibrillation” [AF]. Noting that all other current monitoring tools are either for a limited period or on an intermittent basis, Medtronic said long-term, continuous monitoring “means that a clinician no longer needs to rely only on incomplete data to evaluate how AF may be progressing or treatment effectiveness.”

The Reveal XT Insertable Cardiac Monitor monitors AF patients 24 hours a day, every day for up to three years. Medtronic said that until now, physicians had no means of gathering detailed data, over an extended period, on the progression of AF and the effect of treatment. It said Reveal XT data “may help physicians to evaluate stroke risk and determine appropriate treatment and therapy options for their patients.”

The device recently received CE-mark approval, and the first implant of Reveal XT took place at Asklepios Klinik St. Georg (Hamburg, Germany) by Karl-Heinz Kuck, MD.

“Atrial fibrillation is the most frequent cardiac arrhythmia. It is often accompanied by symptoms that are very unpleasant for the patient,” said Kuck. “Moreover, atrial fibrillation is linked with increased mortality and an increase in the incidence of stroke, by a factor of two- to seven-fold. However, with the new Reveal XT, atrial fibrillation can now be scrutinized over a period of three years with a subcutaneous monitor. This gives us totally new possibilities for monitoring and adjusting the treatment.”

Biotronik finishes enrollment in its first-in-man ProGenic trial

Biotronik (Berlin) reported completing enrollment in the ProLimus I first-in-man trial with its ProGenic pimecrolimus-eluting coronary stent system. The ProLimus I trial is a prospective, non-randomized, multi-center clinical trial with 61 patients enrolled at five sites in Belgium and Germany. Safety and clinical performance of the ProGenic pimecrolimus-eluting stent are evaluated in patients with single de novo coronary artery lesions.

The ProGenic stent is comprised of four elements: The PRO-Kinetic Cobalt Chromium Stent System; the PROBIO silicon carbide passive stent coating as a protective layer that reduces metal ion release and promotes endothelialization; a bioresorbable Poly-L-Lactic Acid polymer drug carrier and what the company termed “the next generation in vascular drug technologies, pimecrolimus.”

Following implantation of the ProGenic stent, drug and polymer is completely absorbed, leaving PROBIO as a long-term safety feature.

Biotronik said the trial is “closer to everyday clinical practice than most first-in-man trials, allowing investigators to include patients with two-vessel disease.”

Clinical follow-up is conducted at 30 days, six months, 12 months and annually up to three years. At the six-month follow-up, all patients will undergo coronary angiography and intravascular ultrasound (IVUS) evaluation.

The primary endpoint of ProLimus I is a composite of major adverse cardiac events (MACE) at six-month follow-up. Secondary endpoints include target vessel revascularization (TVR), in-stent and in-segment binary restenosis, and late lumen loss (both in-stent and in-segment) as measured by angiography.

William Wijns, MD, of Cardiovascular Center Aalst in Belgium, principal investigator of the trial, said, “While eluting a drug having primarily anti-inflammatory effects, the ProGenic stent offers the opportunity for a next step in improving outcomes in the treatment of obstructive coronary artery disease.”

The company said that upon confirmation of favorable results, it will start enrollment of a randomized trial with about 320 patients in 1Q08.

Biotronik’s vascular intervention product line consists of guide wires, balloon catheters and stent systems for coronary and peripheral applications.

NMT’s BioSTAR technology receives CE-mark approval

NMT Medical (Boston) reported receiving CE-mark approval in Europe for its BioSTAR bioabsorbable septal repair implant technology and Rapid Transport delivery system.

President and CEO John Ahern said that BioSTAR “also recently received Canadian regulatory approval and we anticipate initiating a market launch for BioSTAR in both Europe and Canada early in the third quarter.” He added that BioSTAR has been approved for use in MIST II, the company’s pivotal patent foramen ovale (PFO)/migraine trial in the U.S.

BioSTAR is designed to provide biological closure of atrial level defects using the patient’s natural healing response. NMT said data has shown that 90% to 95% of the implant is absorbed over time and replaced with healthy native tissue. It said the data from the prospective multi-center BEST (BioSTAR Evaluation STudy) trial, published in the October 2006 edition of the journal Circulation, demonstrated that BioSTAR provides a more rapid and complete closure of atrial septal defects, with a 92% closure rate at 30 days and 96% at six months.

“BioSTAR represents the first implant in a new generation of bioabsorbable technologies that NMT is developing in order to improve the treatment of structural heart disease,” said Ahern. “As demonstrated by the BEST clinical trial, we believe the unique biomaterial, drug and device combination used in BioSTAR enhances positive septal closure outcomes.

BioSTAR incorporates a purified acellular collagen matrix delivered on the company’s STARFlex alloy framework. The collagen used in BioSTAR also is a platform for timed release of biological response modifiers such as genes, cells, proteins and drugs.

An elutable heparin substrate has been included in the BioSTAR design, which the company said “provides a means to minimize the thrombus formation that occasionally occurs in all intra-cardiac devices.”

• BMEYE (Amsterdam, the Netherlands) reported receiving CE-mark approval for its Nexfin line of hemodynamic monitors, providing continuous non-invasive blood pressure and cardiac output monitoring. The Nexfin family of monitors uses a finger sensor to produce accurate continuous non-invasive blood pressure and cardiac output data displayed on a touchscreen.

“[We were] established to develop and market innovative technology that will transform the practice of medicine in hemodynamic patient monitoring. The CE-mark approval [enables] us to market the Nexfin to cardiologists and any clinician who needs to measure continuous non-invasive blood pressure and cardiac output easily and accurately,” said Bill Bednarski, CEO. BMEYE has offices in Amsterdam and St. Louis.

Boston Scientific’s Taxus Petal trial under way in New Zealand

While key second-generation stent products are under review in the U.S., new stent trials continue to be pursued in other countries around the world.

• Boston Scientific (Natick, Massachusetts) reported launch of its TAXUS PETAL I trial, the first human use of the company’s Taxus Petal Bifurcation paclitaxel-eluting stent system, with implantation in a patient in New Zealand. The procedure was performed by John Ormiston, MD, at Auckland City Hospital.

TAXUS PETAL I will evaluate the safety of a bifurcation paclitaxel-eluting stent platform for the treatment of coronary artery disease (CAD). The trial is a non-randomized study with an initial assessment of acute performance and safety (death, myocardial infarction, target vessel revascularization) at 30 days and six months, as well as continued annual follow-up for five years.

Boston Scientific said that a significant percentage of coronary artery disease — as much as 30% — occurs at a bifurcation, where one artery branches into two smaller arteries. “Bifurcations present a common location for the build-up of plaque and are particularly difficult to treat with currently available stents,” the company said. Taxus Petal is designed to treat both the main branch and the side branch of a y-shaped bifurcation.

“The Taxus Petal Stent enabled us to successfully treat a patient with a difficult bifurcation stenosis,” said Ormiston, principal investigator for the TAXUS PETAL I trial. “Bifurcations are a major challenge in interventional cardiology, and the development of a dedicated drug-eluting bifurcation stent is an important advancement.”

He said the design of the stent provides “consistent mechanical support and drug application not only to the main branch but also to the side-branch ostium, where re-narrowing is common with other techniques used today.”

TAXUS PETAL I will enroll a total of 45 patients in New Zealand, France and Germany. Boston Scientific said that upon successful completion of the study, it intends to begin a pivotal trial to gain U.S. and international approval for the stent.

The stent consists of a traditional DES with a side structure — the Petal Strut — in the middle of the stent that opens into the side branch. The new stent is coated with the proven combination of the paclitaxel drug and Translute polymer.

• Reva Medical (San Diego) reported enrollment of the first patients in a first-in-man clinical trial designed to evaluate the safety of the Reva Bioresorbable Coronary Stent for the treatment of coronary artery disease. The company said the RESORB (Reva Endovascular Study of a Bioresorbable Coronary Stent) trial would enroll up to 30 patients at multiple sites in Germany and Brazil. RESORB is a non-randomized study with an initial assessment of major adverse cardiac events (MACE) at 30 days and a follow-up period of five years. A second trial is planned to study the safety of the Reva Paclitaxel-Coated Bioresorbable Stent in an additional 30 patients.

Principal investigator Dr. Eberhard Grube, of the HELIOS Heart Center Siegburg (Siegburg, Germany), performed the first implants. “Bioresorbable stents offer great promise for the future treatment of cardiovascular disease,” Grube said. “They may be an ideal solution to recent concerns regarding incomplete healing and late-stage thrombosis in stent patients.”

The Reva Stent is intended to act as a temporary scaffold to support the blood vessel during the healing process. Once the vessel has healed, the stent is designed to resorb, leaving the patient free of a permanent implant.

In pre-clinical studies, Reva said its stent geometry and proprietary polymer “have demonstrated mechanical performance similar to metal stents and sustained biocompatibility.”

In 2004, Reva established a relationship with Boston Scientific (Natick, Massachusetts). Hank Kucheman, president of Boston Sci’s Interventional Cardiology Group, said, “We look forward to learning more about the potential of this bioresorbable stent technology.”