November 2007 Clinical and Industry News

Tryton Medical’s Side-Branch Stent Demonstrates Unparalleled 6-Month Angiographic Restenosis Reductions Professor Patrick Serruys, MD, PhD, Presents Cardialaysis Core Laboratory Review of Tryton 1(First-in-Man Study) (n=30): No Side-Branch Restenosis, Late Loss of 0.27± 0.42 mm Tryton Medical, Inc. achieved a major medical milestone in stent technology with unprecedented six-month clinical and angiographic results from the Tryton 1 (First-In-Man Study). Dr. Ralf Muller (Helios Heart Center, Siegburg, Germany) and Professor Patrick W.J.C. Serruys (Erasmus Medical Center, Rotterdam, the Netherlands) presented the clinical and angiographic results at the European Bifurcation Club Meeting in Valencia, Spain. The Tryton Side-Branch Stent was used in conjunction with a standard drug-eluting stent to treat 30 patients with coronary blockages involving large side-branches. After 6 months, none of the patients suffered from side-branch restenosis. Core laboratory quantitative analysis reported a late loss of 0.27 ± 0.42 mm in the side branch and 0.12 ± 0.47 mm in the main vessel. The core angiographic data demonstrates that the hybrid approach, a bare metal Tryton Side-Branch Stent used in conjunction with a standard drug-eluting stent, provides the same type of restenosis reduction we have seen when drug-eluting stents are used to treat standard lesions, said Professor Serruys, Erasmus Medical Center, the Netherlands. The ability to treat bifurcation lesions have been a problem confronting us since the first days of angioplasty, said Dr. Ralf Muller, Helios-Heart Center, Germany. Tryton seamlessly integrates with other aspects of the angioplasty/stent procedure, allowing interventional cardiologists to treat this challenging patient subset with a high level of predictability and ease. The data shows that Tryton’s approach is not only safe, but it reduces restenosis to acceptable levels. I can now treat with confidence, this problem which I confront in nearly 20% of my cases, Muller added. Every year, over half a million bifurcation coronary lesions are sub-optimally treated as no commercially available optimized solution exists for treating bifurcation lesions. As a result, cardiologists are forced to use a provisional strategy which avoids the deployment of a second stent leaving the side branch vulnerable to thrombosis and restenosis. This technology has the capacity to redefine the treatment of bifurcation lesions and resolve a frequent dilemma of the interventional cardiologist, said Dr. Serruys. Bracco Diagnostics Inc. and HealthTrust Purchasing Group Sign a Three-Year Agreement for Contrast Media Bracco Diagnostics Inc., the U.S.-based subsidiary of Bracco Imaging SpA which is part of Bracco Group and HealthTrust Purchasing Group, a healthcare group purchasing organization in the United States, announced a three-year agreement to make Bracco Imaging SpA’s Magnetic Resonance Imaging (MRI) contrast media products available to HealthTrust members through 2010. This agreement includes MultiHance® (gadobenate dimeglumine) injection, 529 mg/mL and ProHance® (gadoteridol) injection 279.3 mg/mL. The agreement is effective September 1, 2007 and extends through August 31, 2010. HealthTrust members with questions regarding the new agreement are encouraged to contact their Bracco Imaging sales representative directly. For full Prescribing Information on both MultiHance and ProHance, please go to https://www.bracco.com/usa/en-US/Imaging/MRI/. Toshiba America Medical Systems Vehicle Fleet Going Green Hybrid Vehicles Further Enhance Commitment to Reducing Carbon Footprint Toshiba America Medical Systems, Inc., offering diagnostic and medical imaging systems, announced its commitment to replacing the company’s entire fleet of sedans for its sales and service teams with hybrid cars over the next three years. As part of Toshiba Corporation’s global environmental initiative, Toshiba chose the Toyota Camry Hybrid to replace one-third of the current gas-only fleet each year. The first set of hybrid cars is scheduled to arrive in mid-to-late November 2007 and will be used by service and sales managers and account executives. With the addition of the Toyota Camry Hybrids, Toshiba expects to reduce fleet CO2 emissions by 25,000 pounds and save approximately $3 thousand to $4 thousand in fuel savings over the lifecycle of each vehicle. The hybrids will take us closer to our goal of reducing emissions in logistics from company cars and freight by one percent each year, said Paul Biggins, director of Regulatory Affairs and head of the TAMS’ Environmental Affairs Committee. Toshiba Corporation has set a global goal of reducing its energy-originated CO2 emissions by 25 percent by 2010 as well as non-CO2 greenhouse gas emissions by 35 percent by 2010. For more information, visit www.medical. toshiba.com. Five-Gene Genetic Risk Score Identified, Predicts Risk of Coronary Heart Disease Findings May Complement Current Clinical Practices for Assessing Risk of CHD Celera, an Applera Corporation business, announced the publication of results from the Atherosclerosis Risk in Communities (ARIC) study and two independent case-control studies, describing the development of a Genetic Risk Score (GRS) based on five gene variants that predicts risk for coronary heart disease (CHD). These variant genes are KIF6, MYH15, PALLD, SNX19, and VAMP8. The GRS of each ARIC participant depended on how many of these risk variants an individual possessed. After adjusting for traditional risk factors, those individuals with a high-risk GRS had a 57% increased risk of incident CHD, which is similar to the magnitude of risk for CHD associated with smoking, hypertension, hypercholesterolemia, or obesity. The study results appeared in the October 2007 edition of Genetics in Medicine, and are available on the journal’s website at https://www.geneticsinmedicine.org. The lead author was Lance Bare, PhD, Associate Director of Cardiovascular Disease at Celera, and the collaborators on the work were investigators from the University of Texas Health Science Center, the Texas Heart Institute, the University of Minnesota, the Cleveland Clinic Foundation, and the University of San Francisco, CA. Physicians need a better assessment of an individual's risk for coronary heart disease than that obtained using traditional risk factors alone, said James T. Willerson, MD, President of The University of Texas Health Science Center at Houston, and President-elect Texas Heart Institute, and a co-author on the study. Applying the results of this research study towards the development of a diagnostic test to determine genetic risk for coronary heart disease could lead to more effective prevention and treatment for patients. The identification of this Genetic Risk Score is a result of a broad collaboration over the past several years involving multiple large studies, said Thomas J. White, PhD, Chief Scientific Officer at Celera. About the Genetic Risk Score. For each of the five variants, the participant’s GRS was increased by 1 if the participant was homozygous (had two copies of the variant) for the risk variant, unchanged if heterozygous (one copy), and decreased by 1 if the individual did not carry the risk variant. Therefore, individuals carrying all 10 possible risk variants were assigned a GRS of 5 and those carrying no risk variants were assigned a GRS of -5. A high GRS was defined as a GRS of 3 or higher. Approximately 4 percent of the Caucasian cohort in the ARIC study was classified as high risk, and this high-risk group had a 52-percent higher CHD event rate compared to the rest of the individuals. A similar trend was observed for African-American participants in the study. About Atherosclerosis Risk in Communities Study (ARIC). The Atherosclerosis Risk in Communities Study (ARIC), sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a large-scale, long-term prospective study with 13 years of follow-up that is being conducted to investigate associations of established and suspected coronary heart disease risk factors with CHD in men and women from four American communities. The project has two components: community surveillance of morbidity and mortality and repeated examinations of a representative cohort of men and women in each community. The community surveillance involves abstracting hospital records and death certificates and investigating out-of-hospital deaths. The 15,792 members of the cohort include African-American and Caucasian males and females, who were 45 to 64 years old at baseline. Bioabsorbable Stents Expected to Enter Coronary Stent Market in 2012 Millennium Research Group forecasts that the bioabsorbable stent, expected to enter the market in 2012, will be used in almost 4% of stent procedures in its first year of use. This device is expected to replace the drug-eluting stent (DES) as the gold standard treatment for patients with coronary artery disease, according to Millennium Research Group’s Emerging Technologies for the Diagnosis and Treatment of Coronary Artery Disease 2008 report. Depending on the outcome of ongoing research efforts, bioabsorbable stents could capture over 80% of stent procedures within 5 years of their release. Fueling this growth will be bioabsorbable stents’ lowered requirement for anti-platelet therapy. Patients find long-term drug regimens to be burdensome, and a small percentage of patients are physically unable to be put on anti-thrombotic drugs due to allergies or other complications. The introduction of bare-metal stents (BMS) in the early 1990s revolutionized the practice of interventional cardiology around the world. Restenosis was, however, a significant obstacle to obtaining effective and long-lasting results with these devices. As a result, firms sought further improvements in stent technology. The 2003 launch of DES in the U.S. reduced restenosis rates to below 10%. Nevertheless, DES use has decreased significantly since recent clinical studies associated metallic stents with late stent thrombosis. The discovery of the heightened late stent thrombosis risk has increased the demand for new variations of DES, such as polymer-free stents, bioabsorbable polymer-coated stents, and above all, fully bioabsorbable stents. In addition to bioabsorbable stents, the Emerging Technologies for the Diagnosis and Treatment of Coronary Artery Disease 2008 report also covers polymer-free and bioabsorbable polymer-coated stents, synthetic coronary artery bypass grafts, remote catheter navigation technology, novel diagnostic imaging technologies, and therapeutic angiogenesis using gene and stem cell therapy. This report includes coverage of industry competitors, including Abbott Vascular, Advanced Cell Technology Inc., Bioabsorbable Therapeutics Inc., Biosensors, BIOTRONIK, Boston Scientific, Cardium Therapeutics, CardioVascular BioTherapeutics Inc., Cytori Therapeutics, Hansen Medical, InfraReDx, MIV Therapeutics, OrbusNeich, REVA Medical, Sahajanand Medical Technologies, Sorin Group, Stereotaxis, Terumo, Thermocore Medical, and more. More information is available on www.mrg.net. Mortality Rates 71% Lower at Top-Rated Hospitals: HealthGrades Annual Hospital-Quality Study Patients have on average a 71 percent lower chance of dying at the nation’s top-rated hospitals compared with the lowest-rated hospitals across 18 procedures and conditions analyzed in the tenth annual HealthGrades Hospital Quality in America Study, issued by HealthGrades, the healthcare ratings company. The study, which documents a wide variation in the quality of care between the highest-performing hospitals and all others, also found that if all hospitals performed at the level of hospitals rated with five stars by HealthGrades, 266,604 Medicare lives could potentially have been saved over the three years studied. The HealthGrades study of patient outcomes at the nation’s approximately 5,000 hospitals covers more than 41 million Medicare hospitalization records over the years 2004 to 2006. The study examines procedures and conditions ranging from heart attack to pneumonia to valve-replacement surgery. Based on the study, HealthGrades made available its 2008 quality ratings for virtually every hospital in the country at www.healthgrades.com, a website designed to help individuals research and compare local healthcare providers. According to the study, mortality rates at America’s hospitals have improved 11.8 percent from 2004 to 2006, with the nation's top-rated hospitals improving at a faster rate (12.8 percent) than the lowest rated hospitals (11.4 percent). Of the 18 procedures and conditions studied, those that saw the most improvement in mortality rates were pancreatitis (19.2 percent), pulmonary embolism (17.4 percent) and diabetic acidosis and coma (16.6 percent). Those with the smallest improvement were resection/replacement of the abdominal aorta (0.4 percent), coronary interventional procedures such as angioplasties and stents (0.8 percent) and treatment of heart attack (8.9 percent). Full reports on mortality rate trends in each of the 50 states and the District of Columbia are available in the study. While we are pleased to see that the hospital industry’s focus on improving care quality has continued to reduce mortality rates, a significant variation in quality among the nation’s best and poorest-performing hospitals persists, said Samantha Collier, MD, HealthGrades’ chief medical officer and one of the authors of the study. Concentrating on emulating practices from exemplary hospitals can result in improvement. If this focus were targeted to four key quality areas heart failure, respiratory failure, sepsis, and pneumonia the nation could achieve up to a 50-percent reduction in potentially preventable deaths. The study also found wide variation in risk-adjusted mortality at the state and regional levels: Across all procedures and conditions, the average number of states performing statistically significantly better than predicted was 14, while an average of 19 states performed statistically significantly worse than predicted. The region with the lowest overall risk-adjusted mortality was the East North Central Region (IL, IN, MI, OH and WI) while the East South Central region (AL, KY, MS and TN) had the highest mortality. The region with the most overall improvement for all procedures and conditions was the West South Central region (AR, LA, OK and TX), where the risk-adjusted mortality dropped by 13.5 percent. The least improvement was seen in the Mountain region (AZ, CO, ID, MT, NE, NV, NM, UT, and WY), with a decline of 8.8 percent. The East North Central region (IL, IN, MI, OH, and WI), had the highest percentage of best-performing hospitals those hospitals that are among the best 15 percent for risk-adjusted mortality overall at 26 percent. Less than seven percent of hospitals within the East South Central region (AL, KY, MS, and TN) and the New England region (CT, ME, MA, NH, RI, and VT) were top-performing hospitals. In the study’s analysis of mortality rates, the following 18 procedures and conditions were analyzed: atrial fibrillation, bowel obstruction, chronic obstructive pulmonary disease, coronary bypass surgery, coronary interventional procedures (angioplasty/stent), diabetic acidosis and coma, gastrointestinal bleed, gastrointestinal surgeries and procedures, heart attack, heart failure, pancreatitis, pneumonia, pulmonary embolism, resection/replacement of the abdominal aorta, respiratory failure, sepsis, stroke, and valve replacement surgery. The full study, along with its methodology and state-by-state hospital-quality statistics, can be found at www.healthgrades.com. Expecting an Afternoon Nap Can Reduce Blood Pressure Where does the benefit lie in an afternoon nap. Is it in the nap itself or in the anticipation of taking a snooze? Researchers in the United Kingdom have found that the time just before you fall asleep is where beneficial cardiovascular changes take place. The finding is part of a study entitled Acute Changes in Cardiovascular Function During the Onset Period of Daytime Sleep: Comparison to Lying Awake and Standing, found in the online edition of the Journal of Applied Physiology, published by The American Physiological Society. The study was conducted by researchers at the Liverpool John Moores University in Liverpool, U.K. Afternoon naps, or siestas, are practiced in many Mediterranean and Latin American countries such as Spain and Argentina. They are typically short naps or rest periods of no more than an hour that are taken in the afternoon. While earlier studies on siestas have found that this practice may slightly increase the risk of heart attack, newer and more controlled studies have shown an inverse relationship between siesta taking and fatal heart attacks. In a recent epidemiological study of 23,000 people in Greece, those who regularly took siestas showed a 37% reduction in coronary mortality compared to those who never nap, while individuals who occasionally napped in the afternoon had a reduction of 12%. Why do afternoon naps affect cardiovascular function? One reason could be changes in blood pressure. At night, our blood pressure and heart rate decreases as we sleep. Some researchers hypothesize that the lower blood pressure reduces strain on the heart and decreases the risk of a fatal heart attack. Most studies have focused on cardiovascular behavior in nighttime sleeping. This study provides a detailed description of changes in cardiovascular function of daytime sleep in healthy individuals, comparing napping with other daytime activities such as standing and lying down without going to sleep. The researchers tested nine healthy volunteers (eight men, one woman) who did not routinely take afternoon naps. The volunteers attended the university laboratory on three separate afternoons after sleeping four hours the night before. The volunteers wore equipment that checked blood pressure, heart rate, and forearm cutaneous vascular conductance (which determines dilation of blood vessels). During one afternoon session, the volunteer spent an hour resting, lying face-up in bed. During another session, the volunteer spent an hour relaxed, but standing. And in one session, the volunteer was allowed an hour to sleep, lying face-up. During the sleep stage, the researchers measured the volunteer’s different stages of sleep. The session in which the volunteer was allowed to fall asleep was delineated into three phases: Phase 1: A five-minute period of relaxed wakefulness before lights were turned off (volunteers had been lying on the bed for a minimum of 15 minutes before this phase) Phase 2: The period between lights out and the onset of Stage 1 sleep (loss of some conscious awareness of the external environment) Phase 3: The period between the Stage 1 and the onset of Stage 2 sleep (conscious awareness of the external environment disappears) Researchers found a significant drop in blood pressure during the sleep trial, but not during the resting or standing trials. What’s more, this drop in blood pressure occurred mostly after lights out, just before the volunteer fell asleep. This reduction in blood pressure may be one explanation for the lower cardiovascular mortality that some studies have found among people who habitually take siestas. On the other hand, some studies of nocturnal sleep have shown that blood pressure rises when we awake and that more cardiac deaths occur in the mornings. The John Moores team plans to study blood pressure during the waking portion of the afternoon nap to see if this period may also pose an increased danger of coronary mortality. Taking the Stress Out of Choosing the Right Stress Test Stress tests are good front-line indicators of heart disease, but just how good depends on ordering the right one, researchers say. Thirty percent of all women, for example, have a false positive exercise treadmill test, in which they walk for several minutes at a slightly increasing incline with an electrocardiogram measuring the electrical activity of the heart, they say. So if you are female, I put you on a treadmill and the waves that measure the electrical activity of your heart drop. You say, ‘Am I going to die?’ says Dr. Vincent J.B. Robinson, nuclear cardiologist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta. That probably is not the case. But instead of then taking those 30 percent of women to the catheterization lab to look for blood vessel blockages, we put them back on the treadmill this time with a contrast medium so we can see the heart work and possibly with a pharmacologic stress agent as well. To help ensure all physicians know the best strategy, a team of MCG cardiologists reviewed the literature on stress tests and wrote a comprehensive article for the October issue of Southern Medical Journal. Coronary artery disease is a very, very prevalent condition and every physician, regardless of specialty, has to face the disease one way or the other, says Dr. Rakesh N. Patel, MCG research assistant who will start a cardiology fellowship in July. A lot of stress tests are available to help assess disease. To maximize the sensitivity and specificity, you have to choose the appropriate stress test. Dr. Patel is the paper’s first author. The paper, complete with algorithms for doing just that, is followed by a quiz that offers continuing medical education credit. Pharmacologic stressors, needed by about half of patients getting stress tests, dilate healthy blood vessels but not diseased vessels, which already are maximally dilated. The addition of a radioactive contrast agent enables heart images where segments fed by healthy vessels glow and diseased areas look like black holes, says Dr. Robinson, the paper’s corresponding author. About one-third of all patients can’t exercise adequately to get good information without those pharmacologic agents. That means being able to walk for at least five minutes and reach 85 percent of maximum age-predicted heart rate: 220 minus age. If you can exercise adequately, it increases blood flow to the heart about twofold, so you don’t need pharmacologic agents, which increase blood flow four- to fivefold, says Dr. Robinson. An exercise EKG is the test we should try first if it’s feasible. However, if a patient can’t walk without pain, shortness of breath or other symptoms that led to testing in the first place, he goes right to stressing the heart with pharmacologic agents. The agents reduce the risk of the test for some patients, because their hearts don’t have to work as hard. In fact, they have been used safely in patients approximately 48 hours after a heart attack, Dr. Robinson says. Without these agents, exercise EKGs have about a 64 percent probability of picking up disease, leaving lots of room for concern if serious disease is suspected, he says. If you perform like an athlete, walk for 12 minutes with no EKG changes, are laughing and have no symptoms, that is a great test. That means your chance of needing revascularization, of having dangerous coronary artery disease that could kill you, is almost zero, Dr. Robinson says. But if you puttered along, got to five minutes and had chest pain but your EKG was still normal, you better believe I would go on to do pharmacologic stress with the perfusion agent. The point here is, in a lethal disease, you cannot accept a 64 percent probability of picking up the disease. In some patients, such as those with pacemakers, exercise EKGs are not even a first option; pharmacologic stress agents alone must be used to perfuse the heart. However, the physicians note that the best images are produced in patients who can also exercise, which pulls blood from the abdomen to the heart, resulting in sharper images. In fact, the MCG researchers have shown pharmacologic agents work even better when given after exercise has started. Picking the right pharmacologic agent can even be an issue. For example, the two most popular agents adenosine and dipyridamole can increase problems such as wheezing, says Dr. Patel. In patients with those problems, physicians opt for dobutamine, the least used agent because it creates a catecholamine surge that causes the heart to shake and blood pressure to rise and can be harmful in patients at high risk of a heart attack. Hand-Held Fluid Aspiration Device FDA Cleared: New PowrSyringe Platform Added to Pinyons Medical Technology Pinyons Medical Technology, Inc. announced it received U.S. Food and Drug Administration clearance to market the PowrSyringe Aspirator. The PowrSyringe Aspirator is a disposable hand-held medical device that incorporates ergonomic and mechanical advantages for fluid aspiration during a variety of medical procedures. The use of a large syringe barrel to aspirate fluids can increase aspiration speed, suction, and volume when compared to a smaller syringe barrel. However, it takes additional user strength and force to pull plungers back when using larger barrels. Therefore, most aspiration procedures require one-hand to hold the barrel and the other hand to pull the plunger back for successful aspiration. The PowrSyringe Aspirator eliminates the need for two hands to perform aspiration. The Aspirator’s design includes handles connected to an integrated syringe barrel and plunger that pull the plunger back when the handles are squeezed. The PowrSyringe Aspirator platform is open-ended with universal connectors in a variety of barrel sizes that are compatible with multiple catheters, needles, and related medical devices. Pinyons is developing a family of PowrSyringe devices for angiography, balloon catheter inflation, spinal discography & vertebroplasty, biopsy, aspiration, and other general applications where fluids are injected or aspirated through small devices to diagnose, treat, or enable other medical devices. The PowrSyringe Monitor is expected to be available for commercial sale in early 2008. U.S. and foreign patents are issued and pending on the PowrSyringe Injector, Monitor, and Aspirator. The PowrSyringe Aspirator is licensed to Pinyons Medical Technology, Inc. by Aspiration Medical Technologies, LLC in Park City, Utah. Pinyons Medical Technology, Inc., www.pinyonsmedical. com has offices in Park City, Utah and Hallandale Beach, Florida. Frost & Sullivan Select Guerbet, Manufacturer of X-ray Contrast Agent Oxilan, for Product Quality Award Frost & Sullivan have selected Guerbet as the recipient of the 2007 North American Frost & Sullivan Product Quality Leadership Award for the superiority of its contrast media products. The company’s flagship product is Oxilan® (ioxilan) Injection, a non-ionic low viscous and low osmolar monomer x-ray contrast agent. Contrast media products in the medical imaging industry encounter several technical and regulatory hurdles, developmental costs, clinical testing, and FDA approval to reach a sellable stage and finally, gain acceptance by end users, says Frost & Sullivan Research Analyst AJ Ajibade. Guerbet has implemented a product development strategy that emphasizes quality and customer satisfaction, with the high quality technical characteristics of its contrast media products embodying the extent of its commitment. Guerbet has Oxilan to thank for its sustained success. Despite the possibility of side effects in injection of x-ray contrast media, Oxilan has achieved remarkably positive usage feedback, confirming it to be a safe product. Based on differences in structure, ionicity, osmolality and viscosity, contrast media are categorized under either monomers or dimers, ionic or non-ionic, low osmolar contrast media (LOCM) or high osmolar contrast media (HOCM) and low viscous contrast media (LVCM) or high viscous contrast media (HVCM). As an LOCM and LVCM, Oxilan shows fewer adverse side effects. Oxilan’s unique molecular structure has a hydrophobic region within its hydrophilic side chain, which leads to molecular aggregation and a reduction in the number of osmotically active particles in solution, explains Ajibade. This results in the lowest osmolality (695mOsm/kg H2O) and viscosity (16.3 mPa.s at 20°C) of all non-ionic monomer contrast media. Each year, Frost & Sullivan presents this Award to the company that has demonstrated superior quality control over their existing competitors in product manufacturing. For more information, visit www.awards.frost.com.

NULL