Clinical & Industry News for March 2010

Women Underrepresented in Clinical Trials Used to Formulate Guidelines More Affected Than Men by Lack of Social Support After Heart Attack Women are substantially underrepresented in clinical trials used to formulate women’s guidelines and are affected more than men by low social support after a heart attack, according to two studies in the women-themed issue of Circulation: Cardiovascular Quality and Outcomes, a journal of the American Heart Association. In an editorial, Viola Vaccarino, MD, PhD, notes that sex-specific research has revealed important differences in the causes, symptoms and treatment of heart disease. But the pool of data is still limited and key questions remain about the development, prevention and treatment of cardiovascular disease in women. “After at least a decade of renewed interest in women’s cardiovascular health, we are left with more questions than answers,” wrote Vaccarino, professor of medicine at Emory University School of Medicine in Atlanta. Cardiovascular disease is the leading killer of U.S. women, causing more than 430,000 deaths per year. Here are highlights of two studies in the themed issue: • In an analysis of 156 randomized clinical trials cited by the American Heart Association’s 2007 guidelines for cardiovascular disease prevention in women, researchers found females were substantially underrepresented compared with how frequently they are affected by various cardiovascular conditions. Overall, women made up just 30 percent of the patient population in the clinical trials used to support the 2007 guidelines. Also, only about one-third of the 156 trials reported sex-specific results. But women account for at least half the deaths in the affected patient populations studied. Among all the trials, women were most represented in those involving hypertension (44 percent of the research population were women vs. 53 percent of all patients with hypertension) and diabetes (40 percent of the research population vs. 50 percent of all patients with diabetes). Representation of women was lowest for heart failure (29 percent of the research population vs. 51 percent of all patients); coronary artery disease (25 percent vs. 46 percent); and hyperlipidemia (28 percent vs. 49 percent). Furthermore, the studies’ enrollment of women varied among classes of therapies being tested, including aspirin, diabetes medications or statins. • In a prospective study examining data from more than 2,400 male and female patients at 19 centers, researchers found that throughout the first year of recovery after a heart attack, low social support was linked with poorer ratings in several measures of physical and mental health — particularly among women. Compared to the group of people who had the highest level of social support at baseline, those with the lowest level faced a higher risk for chest pain, lower quality of life due to heart disease, worse mental functioning and more symptoms of depression. The findings were based on multiple assessments over 12 months. “Our results demonstrate that low social support is linked to important outcomes for patients not only during the early recovery period, but throughout the first year after a heart attack,” said Judith Lichtman, PhD, MPH, senior author and associate professor, Yale School of Medicine, New Haven, Conn. When the researchers compared their data in men vs. women, the association between social support and health in the first year of recovery was stronger for women, particularly for disease-specific quality of life, physical functioning and depression symptoms. Women with low social support were more likely than their peers to be single and have a history of smoking and high cholesterol. Thirty-three percent of the patients in the study were women. Earlier work has linked low social support with higher hospitalization and death rates after heart attack, but the association of social support with other outcomes such as health status and symptoms of depression has not been well studied. The findings are important, “because interventions that increase social support may represent effective, non-invasive opportunities to improve health outcomes within the first year of recovery, particularly for women,” said Erica Leifheit-Limson, M.Phil, lead author and doctoral candidate, Yale University. Vascular Solutions Launches Gator™ ClipSeal Plug Vascular Solutions, Inc. announced the availability of the new Gator™ ClipSeal Plug, designed to maintain a hemostatic seal around 0.035” or 0.038” guidewires within large hemostatic valve introducer sheaths to minimize blood loss. The Gator is intended for use with commonly used 12F to 24F introducer sheaths in procedures such as endovascular aneurysm repair (EVAR) to treat abdominal aortic aneurysms (AAA) or thoracic aortic aneurysms (TAA). The design of the Gator provides an easy and effective solution for minimizing blood loss by side-loading onto the in-place guidewire and securely fitting into the valve of the introducer sheath. The Gator is currently available for sale in the United States through Vascular Solutions’ direct sales force. For more information, visit Volcano Receives FDA Clearance to Market the Eagle Eye® Platinum Digital IVUS Catheter Commercial release in the U.S. is expected in the second quarter of 2010 Volcano Corporation announced that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market the Eagle Eye® Platinum digital intravascular ultrasound (IVUS) catheter in the United States. This catheter offers all of the benefits of the predecessor Eagle Eye Gold catheter, plus improved deliverability and the convenience of additional radiopaque markers. Scott Huennekens, President and Chief Executive Officer of Volcano, commented, “The Eagle Eye Platinum has enhanced deliverability, is significantly easier to use, and includes Volcano’s proprietary virtual histology (VH®) IVUS tissue characterization technology, an imaging modality backed by 15 years of research and data published in over 100 articles, and has been studied in over 10,000 patients.” Vince Burgess, Group President for Advanced Imaging Systems, remarked, “Clinical data continues to illustrate that angiography alone is often not enough to properly assess and treat coronary lesions. The STLLR (The Impact of Stent Deployment Techniques on Clinical Outcomes on Patients Treated with the Cypher™ Stent) trial was a double-blinded clinical study that showed that geographic miss, improperly covering the length of a lesion or vessel blockage, is a contributing factor to poor stenting outcomes, stent thrombosis, and an increased risk of clinical events. In STLLR, where interventions were guided by angiography alone, optimal placement of the stent was achieved in only about half of the procedures. The addition of marker bands is also significant. Although IVUS has been the gold standard for objective measurements of lumen size, plaque composition, and stent expansion, many regular IVUS users still do not use IVUS to make lesion length assessments. Eagle Eye Platinum’s radiopaque markers should provide a quick and easy way for physicians to estimate lengths without the need for a separate pullback device.” Like Eagle Eye Gold, the Eagle Eye Platinum catheter offers fast, plug-and-play functionality, as well as grayscale IVUS, VH IVUS, and ChromaFlo® imaging modalities. GE Healthcare Introduces Vscan™ Pocket-sized Visualization Tool for Point-of-care Imaging GE Healthcare announced the availability of Vscan, a new, pocket-sized visualization tool developed to provide physicians with imaging capabilities at the point-of-care. Roughly the size of a smart phone, Vscan houses powerful, ultra-smart ultrasound technology that provides clinicians with an immediate, non-invasive method to help secure visual information about what is happening inside the body. Vscan is portable and can easily be taken from room to room to be used in many clinical, hospital or primary care settings. The Vscan imaging device received 510(k) clearance in the U.S. by the Food and Drug Administration (FDA), the CE Mark by the European Union, as well as the Medical Device License from Health Canada and is now commercially available in the U.S., Europe, India and Canada. “Having Vscan at my disposal at all times has allowed me to use ultrasound in a number of settings and with patients that I wouldn’t have anticipated before — from the ICU, to the outpatient clinic as well as with ambulatory patients,” said Anthony N. DeMaria, MD, Professor of Medicine, Judith and Jack White Chair in Cardiology and Director, Sulpizio Cardiovascular Center at University of California, San Diego School of Medicine. “Vscan is more than a simple diagnostic tool. The handheld device should help physicians make treatment decisions more quickly. I believe the Vscan technology will play an important role in physical exams.” The ability to take a quick look inside the body using Vscan may help clinicians detect disease earlier. This may prove invaluable in today’s busy practice environment including primary care physicians and those specializing in cardiology, critical and emergency care and women’s health, as well as hospitalists. "During our initial evaluation of approximately 100 patients using Vscan, we have been impressed with its image quality and ease of use,” said Jose L. Zamorano, MD, FESC, Director Cardiovascular Institute University Clinic San Carlos Madrid, Spain. “But even more important than that, we have experienced firsthand the value of adding such a tool to our clinical and physical examination, adding clinically relevant information in roughly one out of every four patients. “ Vscan offers the image quality that until recently was only available with a console ultrasound. Vscan leverages GE’s black and white image technology and color-coded blood flow imaging in a device that fits into a pocket and weighs less than one pound at 3 inches wide and 5.3 inches long. The Vscan is a prescription device for ultrasound imaging, measurement and analysis in the clinical applications of abdominal; cardiac (adult and pediatric); urological, fetal/OB; pediatric; and thoracic/ pleural motion and fluid detection, as well as for patient examination in primary care and in special care areas. Learn more at http:// Vascular Solutions Expands Jiffy™ 0.035” Specialty Guidewire Line Vascular Solutions, Inc. has introduced two new Jiffy™ guidewires, adding both a 120cm and 150cm length to the current 80cm, 0.035” specialty guidewire line. The Jiffy guidewire offers the benefits of both a straight floppy tip and a 3mm J-tip in one double-ended guidewire. The stiff shaft of the Jiffy guidewire provides control and eases wire manipulation for access procedures, while the 10cm graduated transition tip facilitates atraumatic access and device placement. A smooth PTFE pre-coating provides added lubricity. The Jiffy guidewire is currently available in the United States. For more information, visit Use of Multiple Genetic Markers Not Associated With Improved Ability to Predict Risk of Cardiovascular Disease in Women Creation of a genetic risk score comprised of multiple genetic markers associated with cardiovascular disease (CVD) was not associated with significant improvement in CVD risk prediction in a study that included more than 19,000 women, according to a study in the February 17 issue of JAMA. “Risk prediction is a central part of cardiovascular disease prevention and refining prediction strategies remains important for targeting treatment recommendations. One area of potential improvement has been the discovery of genetic markers for cardiovascular disease as well as intermediate phenotypes [physical manifestations] such as cholesterol and blood pressure. Recent efforts using genome-wide association studies have greatly expanded the discovery of genetic markers associated with cardiovascular disease,” the authors write. “While multiple genetic markers associated with cardiovascular disease have been identified by genome-wide association studies, their aggregate effect on risk beyond traditional factors is uncertain, particularly among women.” Nina P. Paynter, PhD, of Brigham and Women’s Hospital, Boston, and colleagues constructed two genetic risk scores based on a comprehensive literature-based selection of genetic markers known to be associated with either cardiovascular disease or an intermediate phenotype and tested the scores to assess their predictive ability. The study included 19,313 initially healthy white women in the Women’s Genome Health Study, followed up over a median (midpoint) of 12.3 years. Genetic risk scores were constructed from the National Human Genome Research Institute’s catalog of genome-wide association study results published between 2005 and June 2009. A total of 101 single nucleotide polymorphisms (SNPs) reported to be associated with cardiovascular disease or at least 1 intermediate cardiovascular disease phenotype were identified and risk alleles (an alternative form of a gene) were added to create a genetic risk score. During follow-up, 777 cardiovascular disease events occurred (199 heart attacks, 203 strokes, 63 cardiovascular deaths, 312 coronary artery revascularizations). After analysis, the researchers found an absolute cardiovascular disease risk of 3 percent over 10 years in the lowest tertile (group) of genetic risk (73-99 risk alleles) and 3.7 percent in the highest tertile (106-125 risk alleles). However, after adjustment for traditional factors, the genetic risk score was not associated with cardiovascular disease risk. “In contrast, family history of premature [heart attack] remained an independent risk factor for incident cardiovascular disease even after adjustment,” the authors write. “We believe these data have clinical relevance for several reasons. First, genome-wide testing is increasingly available and marketed to the general public. Our study finds no clinical utility in a multilocus panel of SNPs for cardiovascular risk based on the best available literature. Second, our data confirm the utility of intermediate phenotypes such as total cholesterol, high-density lipoprotein cholesterol, and blood pressure in as much as genetic risk scores were no longer significant after adjustment for these phenotypes,” the researchers write. “Third, our findings confirm the importance of family history of cardiovascular disease, which integrates shared genetics, shared behaviors, and environmental factors. At the same time, we believe that our data suggest areas for further biomarker research, which may improve prediction.” “While the importance of genetic data in understanding biology and etiology is unchallenged, we did not find evidence in this study of more than 19,000 women to incorporate the current body of known genetic markers into formal clinical tools for cardiovascular risk assessment.” Source: JAMA 2010;303[7]:631-637. Toshiba Service Earns the Most Top Rankings in IMV Servicetrak Imaging Cardiovascular X-Ray User Survey Customers Rank Service on Toshiba’s Cardiovascular X-ray Line No. 1 in 18 Categories In IMV’s 2009 ServiceTrak™ Imaging report on cardiovascular x-ray system service, Toshiba received more top rankings than any other imaging vendor. Toshiba’s cardiovascular x-ray service received the top ranking in 18 out of 36 attributes, including overall service performance, overall satisfaction with a manufacturer, reliability of hardware and reliability of software. Toshiba’s cardiovascular x-ray customers rated categories on a scale of 1 to 6, giving service for Toshiba’s cardiovascular x-ray systems the industry’s highest scores, including 17 average ratings better than 5.0 (“very good”). In the area of Service Performance, Toshiba received the highest score in four out of five categories, including overall service performance, service follow-up, availability of replacement parts, and service performance relative to amount charged. In Phone Support Personnel Performance, Toshiba received the highest score in three out of four categories, including effectiveness of telephone troubleshooting by phone support personnel, degree to which commitments are met by phone support personnel, and percent of the time problem is solved by phone support personnel. In OEM Service Engineer Performance, Toshiba received the highest score in four out of six categories, including timeliness of service engineer arrival on-site, degree to which commitments are met by the service engineer, service engineer competence and service engineer attitude. Clinical Data Presented at JIM 2010 Provide Further Evidence that the Genous™ Bio-engineered R Stent™ Could Be a Treatment of Choice for Patients Not Suitable for Long-Term Dual Antiplatelet Therapy OrbusNeich announced that clinical data presented at the Joint Intervention Meeting (JIM) 2010 in Rome provide further evidence that the company’s Genous stent could be a treatment of choice for patients not suitable for long-term dual antiplatelet therapy. The investigator-initiated, 50-patient, multi-center study evaluated the safety of patients receiving only 10 days dual antiplatelet therapy undergoing stenting with the Genous Bio-engineered R stent. The primary endpoint was the absence of stent thrombosis or any occlusion within three months. Presented by Giuseppe M. Sangiorgi, MD, of the EMO Centro Cuore Columbus and San Raffaele Hospital, Milan, Italy, three-month follow-up data from the Genous in Patients with Reduced Antiplatelet Therapy study show no stent thrombosis of the lesions treated with a Genous Bio-engineered R stent, one case of myocardial infarction, not related to Genous stent implantation, and no sudden cardiac death. “In our institution we use Genous for patients not suitable for prolonged DAPT (dual antiplatelet therapy) or in whom we feel it may have problems with DAPT compliance,” said Professor Sangiorgi. “For these patients and based on the extremely promising results we have had with Genous stent utilization, I believe that this stent can be the optimal compromise we can offer to our patients in terms of efficacy and safety as compared to bare metal or drug-eluting stents.” The study population included patients with de novo coronary artery lesions located in the secondary branch vessel. The primary endpoint evaluated the absence of any occlusion and stent thrombosis of the Genous Bio-engineered R stent within three months, including the angiographic evidence of stent occlusion, myocardial infarction in the area of the stented vessel and sudden cardiac death not attributed to other causes. Genous is OrbusNeich’s patented endothelial progenitor cell (EPC) capture technology that promotes the accelerated natural healing of the vessel wall after the implantation of blood-contact devices such as stents. The technology consists of an antibody surface coating that attracts EPCs circulating in the blood to the device to form an endothelial layer that provides protection against thrombosis and modulates restenosis. The Genous stent is supported by data from more than 5,000 patients in company-sponsored clinical studies. IQ Ranks Among the Strongest Predictors of Cardiovascular Disease, and is Second Only to Cigarette Smoking in Large Population Study While lower intelligence scores — as reflected by low results on written or oral tests of IQ — have been associated with a raised risk of cardiovascular disease, no study has so far compared the relative strength of this association with other established risk factors such as obesity, smoking and high blood pressure. Now, a large study funded by Britain’s Medical Research Council, which set out to gauge the relative importance of IQ alongside other risk factors, has found that lower intelligence scores were associated with higher rates of cardiovascular disease and total mortality at a greater level of magnitude than found with any other risk factor except smoking.1 The findings, published in the February issue of the European Journal of Cardiovascular Prevention and Rehabilitation, are derived from the West of Scotland Twenty-07 Study, a population study designed to investigate the influence of social factors on health. The present analysis was based on data collected in 1987 in a cohort of 1,145 men and women aged around 55 and followed up for 20 years. Data were collected for height, weight, blood pressure, smoking habits, physical activity, education and occupation; cognitive ability (IQ) was assessed using a standard test of general intelligence. When the data were applied to a statistical model to quantify the associations of nine risk factors with cardiovascular mortality, results showed that the most important was cigarette smoking, followed by low IQ. Similar results were apparent when the health outcome was total mortality. The relative strengths of the association were measured by an “index of inequality,” which summarized the relative risk of a health outcome (cardiovascular death) in the most disadvantaged (high risk) people relative to the most advantaged (low risk). This relative index of inequality for the top five risk factors was found to be 5.58 for cigarette smoking, 3.76 for IQ, 3.20 for low income, 2.61 for high systolic blood pressure, and 2.06 for low physical activity. The investigators note “a number of plausible mechanisms” whereby lower IQ scores could elevate cardiovascular disease risk, notably the application of intelligence to healthy behavior (such as smoking or exercise) and its correlates (obesity, blood pressure). A further possibility, they add, “is that IQ denotes ‘a record’ of environmental insults” (eg, illness, sub-optimal nutrition) accumulated throughout life. Commenting on the public health implications of the findings, the study’s principal investigator Dr. David Batty said that the individual skills reflected in a person’s IQ may be important in the management of personal cardiovascular risk.2 “From a public health perspective, there is the possibility that IQ can be increased, with some mixed results from trials of early learning and school readiness programs,” said Dr. Batty. “It may also be worthwhile for health promotion campaigns to be planned with consideration of individual cognition levels.” He also noted that IQ may well be one important factor behind the place of social class as a fundamental determinant of inequalities in health. So far, said Dr. Batty, explanations for such socio-economic gradients in health have traditionally focused on access to resources (such as education and income), physical exposures at home and at work (such as housing conditions and toxins), and health-related behaviors (such as smoking and diet). But studies show that such factors do not fully explain class-based differentials in health. A low IQ, he explained, as suggested in this study, may be a further independent explanation. References 1. Batty GD, Deary IJ, Benzeval M, Der G. Does IQ predict cardiovascular disease mortality as strongly as established risk factors? Comparison of effect estimates using the West of Scotland ‘Twenty-07’ cohort study. Eur J Cardiovasc Prev Rehabil 2010, 17:24–27; DOI: 10.1097/HJR.0b013e328321311b 2. Dr. David Batty is a Wellcome Trust-Funded Research Fellow from the Medical Research Council Social & Public Health Science Unit in Glasgow and the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology.

Society Announcement:

International Council for Certification of Cardiovascular Specialists and Assistants, Inc. (ISMIPSI) merges with the Alliance of Cardiovascular Professionals (ACVP)! All ISMIPSI members have been granted one-year membership with ACVP. ACVP will notify the former ISMIPSI members and will send out membership cards shortly. ACVP will take over conferences, which will become regional. If anyone wishes to setup a regional conference in their community, please contact Pegyy McElgunn, Esq, Executive Director, ACVP (www.acvp-online) at 804-639-9213 or by email: peggymcelgunn The regional conferences will focus on the mid-level RCSA program. ISMIPSI has become the International Council for Certification of Cardiovascular Specialists and Assistants, Inc., 2500 Metrocentre Blvd, Suite 6-C, West Palm Beach, FL 33407. The General Manager is Christina Morris. She can be contacted at christinamorris777 or by phone: (352) 843-7711. The ISMIPSI website will be completed shortly. Study Examines Course and Treatment of Unexplained Chest Pain Fewer than half of individuals who have “non-specific” chest pain (not explained by a well-known condition) experience relief from symptoms following standard medical care, according to a report in the February 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. In addition, one-tenth of those with persistent chest pain undergo potentially unnecessary diagnostic testing. More than half of patients with chest pain are classified as not having an underlying heart condition. Some have another well-established medical condition, such as upper respiratory tract infection, but for many no pathophysiologic cause can be found. Such non-specific chest pain “is a frequent phenomenon in primary care,” the authors write. “However, knowledge about the course and outcome of this condition is sparse.” Julia Anna Glombiewski, PhD, of Philipps-University of Marburg, Germany, and colleagues studied 807 patients (average age 57.6 years) with non-specific chest pain who visited 74 German primary care offices in 2005 and 2006. The clinicians recorded their preliminary diagnoses, along with any investigations and treatments related to their patients’ chest pain. Patients were contacted by phone six weeks and then six months after the initial consultation. Among the 755 study patients who provided data at the six-month follow-up, 419 (55.5 percent) still had chest pain. In addition, 45 (10.7 percent) of those were categorized as using health care in an inappropriate manner, defined as two or more visits to a cardiologist or three or more cardiac diagnostic evaluations — including angiograms and electrocardiograms — within six months. This compared with 24 (7.1 percent) of 336 patients with remitted chest pain. Only six patients, less than 2 percent, were referred to mental health specialists for ongoing chest pain. “This finding is surprising because psychological factors are known to contribute to the development of chronic pain, and psychological consultations are covered by the health care system in Germany,” the authors write. “Patients with psychologically caused non-specific chest pain showed more problematic health care–seeking behavior but were rarely referred to mental health professionals. Patients, general practitioners or both seem to be hesitant to involve psychological interventions.” The findings help explain the high prevalence of chest pain in the general population, the authors conclude. “Future research should investigate the development of effective interventions for non-specific chest pain and their implementation within health care systems.” Source: Arch Intern Med. 2010; 170[3]: 251-255. Reduced Kidney Function and High Levels of Protein in Urine Associated With Increased Risk of Death, Heart Attack and Kidney Failure Patients with high levels of proteinuria (protein in urine) in addition to another marker of reduced kidney function had an associated increased risk of all-cause death, heart attack or progression to kidney failure, according to a study in the February 3 issue of JAMA. As many as 26 million Americans have chronic kidney disease (CKD). The current system for determining the stage of CKD is based primarily on the estimated rate of glomerular filtration (eGFR) with lower eGFR associated with higher risk of adverse outcomes. The authors write, “… the guidelines have been criticized because they do not incorporate information about the presence and severity of proteinuria an important marker of CKD that is associated with adverse outcomes.” Brenda R. Hemmelgarn, MD, PhD, of the University of Calgary, Alberta, Canada, and colleagues examined the association between reduced eGFR, proteinuria, and adverse clinical outcomes, including all-cause death, heart attack, and progression to kidney failure. The researchers analyzed data from a province-wide (Alberta) laboratory registry that included eGFR and proteinuria measurements for 2002 to 2007. There were 920, 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment (i.e., dialysis) at the beginning of the study. The researchers found that within each level of eGFR, there was substantial variability in risk with participants who had greater amounts of proteinuria having increased adjusted rates of all 4 adverse outcomes (all-cause death, heart attack, end-stage renal disease, and the doubling of serum creatinine measurement [corresponding to a 50 percent decline in kidney function]). Patients with heavy proteinuria but without overtly abnormal eGFR appeared to have worse clinical outcomes than those with moderately reduced eGFR but without proteinuria. Significant interactions between eGFR and proteinuria were observed for death, initiation of renal replacement, and doubling of serum creatinine. “These findings are important because current guidelines for the classification and staging of CKD are based on eGFR without explicit consideration of the severity of concomitant proteinuria. In addition, computerized reporting of eGFR (generally without consideration of proteinuria) is increasingly used to assist physicians in identifying patients at high risk of adverse outcomes — or those who might benefit from specialist care. Although our findings do not directly address which patients would benefit from referral to a nephrologist, they do suggest that risk stratification performed in terms of eGFR alone is relatively insensitive to clinically relevant gradients in risk,” the authors write. “These findings suggest that future revisions of the classification system for CKD should incorporate information from proteinuria.” Source: JAMA 2010;303[5]:423-429. Stentys Drug-Eluting Self-Expanding Coronary Stent Shows 4% Restenosis in Complex Lesions Stentys announced that the complete ‘OPEN-I’ clinical study was presented by Stefan Verheye, MD, PhD, at the Joint Interventional Meeting (“JIM”) 2010 in Rome, demonstrating superior results in 60 patients (27 Stentys drug-eluting stents and 33 Stentys bare-metal stents) who were followed up angiographically after six months. “These clinical results suggest very promising benefits for patients,” said Stefan Verheye, MD, PhD, Department of Cardiology, Middelheim Hospital, Antwerp, Belgium. “We had already demonstrated that the self-expanding and disconnectable Stentys platform ensured optimal wall apposition and easy access to side branches. We can now confirm that the addition of a drug coating eliminates the need for reintervention.”