Clinical and Industry News

Boston Scientific Announces FDA Clearance For New IQ Guide Wire Boston Scientific Corporation has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market its new coronary IQ Guide Wire in the United States. The Company will launch the product immediately. The Company’s IQ Guide Wire is designed to provide physicians control in a variety of situations. The Company also announced the availability of the IQ Marker Guide Wire, which features two 5 mm markers. Both the IQ and the IQ Marker Guide Wires are available in 185 and 300 cm lengths, and in both straight and J-tip configurations. The IQ Guide Wire complements Boston Scientific’s PT2 Guide Wire, which is designed for use in more difficult cases such as tight lesions or multivessel disease. Heart Disease Risk Factors Rooted in Childhood According to two new studies, lifestyle factors that increase the risk of heart disease in adults begin to take hold in childhood, and possibly even prior to birth. In one study, Boston researchers found that about two-thirds of 1,960 adolescents studied had at least one risk factor for heart disease, and almost 10% had metabolic syndrome. In the other study, British and Australian investigators looked at parental and early-life characteristics and their association with blood pressure in 5-year-old offspring. The children of women who smoked during pregnancy had higher blood pressure compared to children of nonsmokers, and parents’ weight also influenced blood pressure. Breast-feeding was associated with a lower blood pressure. Collectively, the findings suggest a need to start heart disease prevention efforts early, rather than after risk factors have become well established. Sarah de Ferranti, MD, MPH, a researcher from the cardiology division at Children’s Hospital Boston, notes, [Medical] practitioners should be aware of the clustering of metabolic abnormalities in children, and affected children should receive risk-reducing interventions. The metabolic syndrome is defined by the presence of multiple heart disease risk factors (at least 3): impaired fasting glucose, high blood pressure, low HDL, elevated trigylcerides, and obesity (measured by waist circumference). The metabolic syndrome has been studied extensively in adults, but far less in children and adolescents. Researchers adapted the criteria for adult metabolic syndrome to children, then applied them to participants aged 12-19 years in the third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994. Overall, 63.4% of the children and teenagers had at least one metabolic abnormality, said researcher Nader Rifai, PhD. Nearly one-third (31.2%) of overweight/obese adolescents had the metabolic syndrome. The most common risk factor was a low level of HDL cholesterol, seen in more than 40% of boys and girls. About 30% of adolescents had elevated levels of triglycerides, and between 20% and 30% of adolescents had a waist circumference that met the definition of obesity. Additionally, 9.2% met the criteria for metabolic syndrome, which occurred almost equally in boys (9.5%) and girls (8.9 %), and in older (8.3%) and younger (10.3%) adolescents. The distribution of metabolic syndrome by ethnic group was Mexican-Americans, 12.9%; non-Hispanic whites, 10.9%; and non-Hispanic blacks, 2.5%. These percentages for adolescents are similar to those reported in adults from the same ethnic groups. In the second study, Debbie A. Lawlor, MB, ChB, PhD, consultant senior lecturer in epidemiology, department of social medicine, University of Bristol, United Kingdom, and colleagues, reviewed parental and early-life factors that influenced blood pressure in children at age 5. Interest in blood pressure at such an early age comes from the recognition that blood pressure in adults tends to follow the same pattern seen in childhood. The study involved more than 8,500 Australian women and their offspring enrolled in the Mater-University (Queensland, Australia) study of pregnancy and outcomes. The investigators evaluated a variety of variables for their potential influence on childhood blood pressure. The factors included ethnicity, smoking history, mother’s height and weight, father’s body mass index, family education, income and a variety of other factors. Offspring (3,864) were examined at age 5. Children of women who had smoked throughout pregnancy had a systolic blood pressure that was about 1 millimeter of mercury (mm Hg) higher at age 5, compared to children whose mothers did not smoke during pregnancy. A comparison of women who quit smoking during pregnancy with those who continued suggested that quitting during pregnancy could prevent the adverse effect on offspring blood pressure. A mother’s age was associated also with higher blood pressure. A child’s systolic blood pressure was 0.7 mm Hg higher for every additional five years of age in women at the time they gave birth, Lawlor said. Breast-feeding for at least 6 months was associated with lower blood pressure. Other factors associated with blood pressure were the mother’s weight and height, the father’s weight, and the child’s weight, height, and body mass at age 5. Cardiovascular Experts Review Ethical Issues in Research and Health The American College of Cardiology (ACC)/American Heart Association (AHA) Bethesda Conference on Professionalism and Ethics represents the consensus of 66 recognized experts. The document also will be available to the public on www.acc.org/clinical/ consensus/ethics/index.pdf and circ.ahajournals.org. Cardiology opinion leaders tackled such tough topics as researchers’ relationships with industry, adequate diversity in populations participating in clinical research, and ensuring all results of clinical trials, both negative and positive, are made available to the public. Conflicts of interest continue to dominate discussions regarding medical ethics. The ACC and AHA recommend that physicians and physician investigators fully disclose any relationships with industry. This particularly applies to authors of research studies. The conference also addressed the issues of multiple tests and procedures now available for diagnosing and treating cardiovascular disease. It is very important when tests are recommended for patients that they are chosen to ensure the greatest possible benefit. Conference participants also urge cardiologists to actively participate in clinical trials and to ensure that they adequately recruit patients traditionally underrepresented in such trials, especially women, the elderly and minority groups. Additional suggestions encourage cardiologists to provide expert medical opinion for malpractice and other litigation cases. Trial Studies Exercise Role in Relieving Peripheral Arterial Disease While physicians often recommend exercise to help relieve the symptoms of peripheral arterial obstructive disease (PAOD) a potentially debilitating disorder that afflicts one in eight Americans they have done so without fully understanding why it seems to help. However, a new clinical trial led by Duke University Medical Centers aims to supply the scientific basis for this clinical practice. Clinicians have long appreciated that exercise in general can stimulate formation of new blood vessels in skeletal muscle, a process known as angiogenesis. The Duke researchers, collaborating with colleagues at the University of Colorado Health Sciences Center, Denver, believe that this angiogenic response to exercise underlies the improvements in walking endurance and symptom relief of PAOD patients. The Duke team is now enrolling patients in a clinical trial to test this hypothesis. The trial is supported by the five-year, $3.9 million grant from the National Heart Lung Blood Institute. Almost every physician will recommend exercise for their patients with peripheral arterial obstructive disease, but the reality is that we don’t really know why it works, said Duke cardiologist Brian Annex, MD, principal investigator for the trial. If we can understand why exercise works, it would be much easier to make our treatments more effective. It is estimated that between 8 and 12 million Americans suffer from PAOD, an incidence that is slightly less than coronary artery disease. While many patients with PAOD also have coronary artery disease, Annex said that almost half of them have no heart disease. While up to three-quarters of patients do not report symptoms, there is a simple test to screen for PAOD. The ankle-brachial index (ABI), which is the ratio of the blood pressure recorded at the ankle and the arm, can often detect the presence of PAOD. The American Diabetes Association recommends that all diabetics receive annual ABI testing after the age of 50 to screen for PAOD. For the trial, which is recruiting patients at Duke and the University of Colorado, researchers plan to enroll 160 participants, equally divided among men and women. These patients will be randomized to either an individualized exercise program conducted at home or to a supervised exercise program on campus. An additional 66 age-matched participants will be recruited to serve as controls by not exercising. An important goal of this trial is to document the gender differences in the disease and the responses to exercise, Annex said. In the past, women have been horribly under-represented in PAOD studies, even though the incidence of the disease in women is similar to men. The results of our trial should help to establish whether current exercise prescriptions are adequate for both men and women with PAOD, or whether different therapeutic strategies are needed. Because of this focus on gender, the National Institutes of Health’s Office of Research on Women’s Health is a co-sponsor of the trial, which has been named Angiogenesis and Mechanisms of Exercise Training in PAOD (AMNESTI). During the three-month trial, researchers will make detailed measurements at regular intervals using ABI, magnetic resonance imaging and muscle biopsies to determine if exercise is indeed stimulating the growth of new vessels, and furthermore, if these changes correlate with improvement of symptoms. The researchers will follow such markers as the growth of new capillaries in leg muscles, the occurrence of programmed cell death (apoptosis) within leg muscle, and blood levels of vascular progenitor cells, which are produced in the bone marrow and are responsible for blood vessel repair. Limiting Angioplasty to Experienced Hospitals Will Not Reduce Access to Care Standards of volume that limit angioplasty procedures to more experienced hospitals and physicians will not require most patients to travel longer distances for care, according to a new study by researchers at Duke University Medical Center and Duke’s Fuqua School of Business. The findings should allay concerns about the effects of such standards on access to care for heart patients living in rural or remote areas, the researchers said. Earlier studies have found that patients receiving angioplasty treatment at higher-volume hospitals have better outcomes than those at smaller or less experienced hospitals, said Kevin Schulman, MD, director of the Duke Center for Clinical and Genetic Economics and of the Health Sector Management Program at Fuqua. The American College of Cardiology (ACC) therefore recommends that hospitals perform at least 400 angioplasty procedures annually and that practicing physicians perform at least 75 procedures annually. For the vast majority of patients, travel distances would remain unchanged should those receiving care at low-volume hospitals be diverted to facilities that meet such minimum requirements, the team reported. At operator and hospital levels, higher procedure volume is associated with lower rates of inpatient mortality, emergency bypass surgery and complications, said study researcher Susan Kansagra of Duke. Accordingly, patient outcomes could be improved by requiring hospitals and physicians to meet minimum standards. Our findings suggest that limiting angioplasty to higher-volume hospitals would not increase travel distances for most patients, added Lesley Curtis, PhD, a member of the Duke Center for Clinical and Genetic Economics, who also contributed to the research. However, they caution that other potential costs of restricting angioplasty to more experienced centers such as possible effects on the ability of smaller hospitals to provide other healthcare services must be examined before recommending such a policy. The researchers examined hospital discharge records for 97,401 patients who underwent angioplasty in New York, New Jersey and Florida in 2001. For each patient, the team approximated travel distances to area hospitals as the distance between their home and hospital zip code areas. Eighty-seven percent of patients would have traveled approximately the same distance to the nearest eligible hospital, if a minimum volume standard of 75 angioplasty procedures per physician and 400 per hospital had been in effect, as recommended by the ACC, the researchers found. Two percent of patients would have traveled farther to reach an angioplasty facility and 11 percent would have traveled a shorter distance. With a stricter minimum volume standard of 175 angioplasties per physician and 400 per hospital, 25% of patients would have traveled a shorter distance to the hospital and ten percent a longer distance. The remaining 65% of patients would have experienced no change in travel distance to the nearest qualifying facility, the team reported. Most patients with longer travel distances under such a strict standard would travel no more than 25 miles farther to reach the nearest high volume hospital, they found. Under either standard, less than one percent of patients would travel more than 50 miles farther than their observed travel distance, they found. The only other studies known to address the impact of minimum volume standards on travel distances all for procedures less common than angioplasty, including pancreas and esophagus removal, coronary bypass surgery and pediatric heart surgery have reported small increases in travel distance or time for the majority of patients. Magnetic Resonance Tomography for Overweight Patients Siemens has developed a magnetic resonance tomography (MR) scanner that is specially designed to accommodate obese patients. Featuring an open tunnel, the Magnetom Espree not only offers enough space for the overweight but also provides a less stressful environment in which to examine people who suffer from claustrophobia. It is the only system of its kind worldwide and is in operation at the renowned Mayo Clinic in Jacksonville, Fl. Particularly in countries such as the U.S., where almost two-thirds of all adults are overweight, the Magnetom Espree could help ensure that all categories of patient have access to the same level of healthcare. The overweight are especially prone to cardiovascular conditions and problems with the locomotor system. The new system is able to provide a more reliable diagnosis of such ailments. Conventional open MR scanners function at most with a magnetic field of 0.7 teslas, which with corpulent patients is often insufficient to provide an adequate image quality. By contrast, the Magnetom Espree, like other current high-field systems, functions at 1.5 teslas and therefore produces images of a substantially better quality. With a diameter of 70 centimeters, the tunnel opening is around 10 centimeters larger than other 1.5-tesla systems. The scanner is only 125 centimeters long, and the patient’s head remains outside of the unit for most types of examination, which is of benefit to sufferers of claustrophobia. Radi Medical Systems Presents New Generation PressureWire® Sensor for Fractional Flow Reserve Measurement Radi Medical Systems (Radi) has introduced the PressureWire®5 Sensor for Fractional Flow Reserve (FFR) measurement. The new PressureWire®5 Sensor has significantly improved overall maneuverability, pushability and a new tip design with improved shape retention, valuable during long and complex procedures. Radi’s physiology platform is the only system on the market that provides measurement of pressure (FFR), flow (CFR) and intravascular temperature using a single PressureWire® Sensor and one instrument. All data is easily transferred to a PC for data transfer and storage. PressureWire5 Sensor has received FDA 510(k) clearance for sales and distribution in the U.S. Spectranetics Enrolls First U.S. Patient in Extended FAMILI Feasibility Trial for Heart Attack Patients Spectranetics Corporation has initiated U.S. patient enrollment in their Extended FAMILI (Flow in Acute Myocardial Infarction after Laser Intervention) feasibility clinical trial. The feasibility trial will enroll 80 patients at up to 20 multi-national sites. To date, a total of 40 patients have been enrolled, with 39 being enrolled at seven European sites. The first U.S. patient was enrolled at Pinnacle Health Systems, Harrisburg, PA, with the procedure being conducted by Rajesh Dave, MD. The patient was a 72 year-old male who presented with an acute myocardial infarction due to a complete blockage in the left coronary artery. Dr. Rajesh Dave commented, I’ve always believed that ablating thrombus and ruptured plaque with excimer laser technology improves the likelihood of attaining TIMI 3 flow, as well as reduces the potential for complications such as ‘no reflow’ after stent implantation. In my first case within Extended FAMILI, we attained TIMI 3 flow after only a single pass with a 0.9 millimeter laser catheter. We followed this with a larger 1.4 millimeter laser catheter to further open the vessel and provide a higher chance of attaining a superior outcome with stent implantation. I am very pleased to see excimer laser now being examined in acute myocardial infarction patients. Dr. Dave reported there were no complications. ‘Heart Attack Gene’ Discovered at Cleveland Clinic Exists in 1“2% of U.S. Heart Patients In November 2003, Cleveland Clinic researchers announced the discovery of the first gene confirmed as a cause of coronary heart disease in humans. Less than a year later, their studies indicate this heart attack gene is more prevalent among Americans than expected. According to their findings, as many as 1 percent to 2 percent of all U.S. heart attack and coronary artery disease patients may carry mutations of the MEF2A gene. Cleveland Clinic researchers discovered this gene by methodically studying the genetic makeup of 21 members of an Iowa family plagued for generations by heart disease. When researchers initially discovered an MEF2A deletion mutation in the Iowa family, they acknowledged it was unlikely that the exact genetic mutation would be found in other people. Instead, they began to search for smaller mutations involving the same gene, and they found just that. The latest mutation involves three novel mutations in exon 7, rather than exon 11 as in the original MEF2A mutation. The new mutations also involve one base pair point change, instead of a 21 base pair deletion. This is another exciting and vital piece in the heart-disease puzzle, said Eric J. Topol, MD, chairman of the Department of Cardiovascular Medicine at The Cleveland Clinic. This study indicates that coronary artery disease and heart attack can result from a spectrum of MEF2A mutations. This work along with that of other groups will quickly solve the genetic bar code for coronary disease, greatly enhancing our efforts to prevent it or make an early diagnosis. Dr. Topol, who also serves as the Clinic’s provost and chief academic officer, said the study indicates that a significant number 1.93% of the population suffering from coronary artery disease or heart attack may carry MEF2A mutations. The MEF2A gene makes a protein that controls the expression of hundreds or even thousands of other genes in the endothelium. Cleveland Clinic scientists suspect the resulting genetic changes weaken the endothelium, making it more susceptible to invasions and attacks by monocytes and macrophages. For the latest study, researchers reviewed the genetic data of 207 patients with coronary artery disease/heart attack and 191 patients with normal angiograms as a control group. No MEF2A mutations were detected in the control group, however three novel mutations were identified in four of the 207 coronary artery disease/heart attack patients (1.93 percent). Researchers concluded the gene carriers with loss-of-function mutations appear to be associated with less severe coronary artery disease and did not develop heart attack, as did the Iowa family with a more severe mutation. This supports the theory that a range of mutations is likely and that a range of corresponding outcomes exists. Further study will be needed to define the actual prevalence of MEF2A mutations. Identifying new mutations in the MEF2A gene is a significant finding because it brings us one step closer to unlocking the genetics behind heart disease and heart attack, said Qing Wang, PhD, director of The Cleveland Clinic’s Center for Cardiovascular Genetics. The finding that 1 percent to 2 percent of the heart disease population have mutations in MEF2A also is significant because it brings us closer to the development of a future genetic testing kit for these patients. Aggressive lifestyle modifications and preventive therapies will help patients to prevent or delay the onset of heart attacks. Guidant Begins Enrollment in New Study of Carotid Stenting CAPTURE Will Advance Understanding of Carotid Stenting In High-Risk Patients at 150 U.S. Sites Guidant Corporation has begun enrollment in CAPTURE (Carotid Acculink/Accunet Post Approval Trial to Uncover Rare Events), an FDA-required post-approval study of carotid artery stenting performed by physicians from multiple specialties. The study will utilize Guidant’s carotid stent and embolic protection system. As announced in its final decision, the Centers for Medicare & Medicaid Services (CMS) will provide expanded payment coverage to include high-risk patients treated as part of this and other FDA-required post-approval studies of carotid artery stenting. CAPTURE is part of Guidant’s post approval study plan that will include at least 1,500 patients receiving Guidant's FDA-approved Acculink Carotid Stent System and Accunet Embolic Protection System at approximately 150 sites in the United States. The primary endpoint of the study will be a composite of stroke, death and heart attack at 30 days following the carotid stenting procedure. Guidant’s devices will be available only to physicians with the appropriate training and prerequisite experience for performing carotid interventions. The company has worked closely with the FDA, medical societies and leading practitioners to develop targeted training programs in the use of the Acculink/Accunet Systems for physicians, based on their experience level. Experimental Lupus Drug May Also Work Against Atherosclerosis A drug that reduces symptoms of systemic lupus in mice may turn out to be effective against atherosclerosis, according to two poster presentations at the American College of Rheumatology meeting in San Antonio. Nilamadhab Mishra, MD, of Wake Forest University Baptist Medical Center, said the drug, called Trichostatin A or TSA, may have a therapeutic benefit in atherosclerosis. Mishra, assistant professor of internal medicine - rheumatology, and his colleagues tested TSA on experimental mice that were bred to lack a significant natural protection against atherosclerosis. For 12 weeks, these mice were fed a diet that was both high in cholesterol and in which 10 percent of calories came from palm oil, one of the vegetable oils most likely to cause atherosclerosis. In addition to the coronary arteries, atherosclerosis also occurred in the aortic arch. When Mishra compared the mice given TSA with mice given an inert substance, the amount of atherosclerosis deposited in the aortic arch was cut in half. The TSA-treated mice also had a reduction in total and free cholesterol levels in the abdominal aorta. These mice had a three-fold reduction in the gathering of macrophages. The recognition of atherosclerosis as an inflammatory disease raised the question of whether anti-inflammatory drugs might decrease this disease process, said Mishra, who noted that TSA is not only an anti-cancer and anti-lupus drug, but also an anti-inflammatory agent. TSA treatment changed the composition of the atherosclerotic deposit in a way that may lead to plaque stability. Mishra got similar results when he tested TSA on another type of experimental mice that are also prone to atherosclerosis. He said a gene called CD154 causes both atherosclerosis and lupus. This drug inhibits both. Coffee Tied to Inflammation, Perhaps Heart Disease Consuming moderate-to-high amounts of coffee is associated with increased levels of several inflammatory markers, a finding that could help explain previous reports linking the beverage to heart disease. The latest findings are based on a study of about 3000 subjects with no history of cardiovascular disease. A food-frequency questionnaire was used to assess coffee intake, and blood samples were tested for levels of various compounds that are known to promote, or are a marker of, inflammation. Compared with subjects who did not drink coffee, those who consumed more than about 1 cup of the beverage per day had significantly higher levels of all the inflammatory markers tested, Dr. Demosthenes B. Panagiotakos, from Harokopio University in Athens, and colleagues report. The results held true even after factoring in age, gender, smoking, body weight, physical activity, and other potential confounders, the researchers point out. Although the findings provide a mechanism by which coffee intake could promote heart disease, the authors note that not all previous studies have identified an association between the two. Hence, further studies are needed to confirm the present findings.

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