Clinical and Industry News

News

Compiled by CathLab Digest
Compiled by CathLab Digest

FDA Advisory Committee Votes Favorably on Expanding the Indication for Abbott’s Carotid Stent System to Include Patients at Standard Surgical Risk

Abbott announced that the U.S. Food and Drug Administration (FDA) Circulatory System Devices Panel of the Medical Devices Advisory Committee voted that, for symptomatic and asymptomatic carotid artery disease patients at standard surgical risk, there is reasonable assurance that the benefits of the Rx Acculink® Carotid Stent System outweigh its risks (Yes: 7, No: 3, Abstain: 1). Currently, Rx Acculink is approved for the treatment of symptomatic and asymptomatic patients at high risk of adverse events from carotid endarterectomy (surgery). The FDA will take into account the panel’s advice in making its decision on whether to expand Rx Acculink’s current indication to include patients at standard surgical risk; the company expects a decision later this year. The committee’s recommendation followed a review of data from CREST (Carotid Revascularization Endarterectomy vs. Stenting Trial), the largest prospective study conducted to date comparing stenting to surgery. CREST demonstrated that carotid artery stenting and carotid surgery had similar safety and long-term outcomes for patients with symptomatic and asymptomatic carotid artery disease who were at standard surgical risk. In an analysis of 2,307 standard-risk patients with symptomatic and asymptomatic disease, carotid artery stenting demonstrated non-inferiority to surgery for the primary composite endpoint of death, any stroke and myocardial infarction (heart attack) within 30 days of the procedure plus ipsilateral (same side) stroke from 31 to 365 days. The results showed 7.1 percent of stenting patients and 6.6 percent of surgery patients experienced an event, the difference being non-significant. The Rx Acculink Carotid Stent System, used in conjunction with the Rx Accunet® Embolic Protection System, is indicated for the treatment of patients at high risk of adverse events from carotid endarterectomy who require carotid revascularization and meet certain criteria. Additional information about the Rx Acculink carotid stent system, including important safety information, is available online at www.abbottvascular.com/static/cms_workspace/pdf/ifu/carotid_intervention/RX_Acculink_Carotid_Stent_System.pdf
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Vascular Solutions Introduces the OptiSeal Valved Peelable Introducer

Vascular Solutions, Inc. announces the immediate availability of the OptiSeal valved peelable introducer, a unique, ergonomic peel-away introducer sheath to facilitate placement of device leads and catheters in the venous system. The OptiSeal combines a sheath constructed from PTFE with a proprietary valve for optimal insertion and sealing, preserving the integrity of the lead or catheter. The locking hub prevents separation of the sheath and dilator during insertion into the vessel, and a smooth sheath-to-dilator transition provides atraumatic vessel access. The OptiSeal system advances safety and simplicity, with symmetric, ergonomically designed handles allowing for a smooth, unidirectional crack and peel, designed to reduce risk of air embolism as well as limit the clinician’s exposure to blood-borne pathogens. Each OptiSeal system contains a 13cm peel-away valved introducer sheath with a locking dilator, a 60cm 0.035” guidewire, an 18-gauge needle, and a 12cc syringe. OptiSeal introducers are available in seven sizes, from 6F to 12F, color-coded by French size for easy identification. The OptiSeal valved peelable introducer is intended for use in the percutaneous insertion of pacing leads or catheters in the venous system, and is available in the United States through Vascular Solutions, Inc. For more information, visit www.vascularsolutions.com
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AHA: Updated Heart Disease Prevention Guidelines for Women Focus More on “Real-World” Recommendations Than Clinical Research

Practical medical advice that works in the “real world” may more effectively prevent cardiovascular disease in women than recommendations based only on findings in clinical research settings, according to the 2011 update to the American Heart Association’s cardiovascular disease prevention guidelines for women. First published in 1999, the guidelines until now have been primarily based on findings observed in clinical research. That alone often doesn’t consider the personal and socioeconomic factors that can keep women from following medical advice and treatment. “These recommendations underscore the fact that benefits of preventive measures seen day-to-day in doctors’ offices often fall short of those reported for patients in research settings,” said Lori Mosca, MD, MPH, PhD, chair of the guidelines writing committee and a medical advisor for the American Heart Association’s Go Red For Women movement. “Many women seen in provider practices are older, sicker, and experience more side effects than patients in research studies. Factors such as poverty, low literacy level, psychiatric illness, poor English skills, and vision and hearing problems can also challenge clinicians trying to improve their patients’ cardiovascular health.” The 2011 update identifies barriers that hinder both patients and doctors from following guidelines, while outlining key strategies for addressing those obstacles. “Awareness continues to be a key driver to optimal care,” said Mosca, director of preventive cardiology at New York-Presbyterian Hospital and Professor of Medicine at Columbia University Medical Center. “Cause initiatives such as Go Red for Women and provider compliance programs such as Get With The Guidelines® are strong components in our efforts to broaden awareness and improve adherence among patients and providers.” She said getting a dialogue started between a woman and her doctor is a critical first step. “If the doctor doesn’t ask the woman if she’s taking her medicine regularly, if she’s having any side effects or if she’s following recommended lifestyle behaviors, the problems may remain undetected,” she said. “Improving adherence to preventive medications and lifestyle behaviors is one of the best strategies we have to lower the burden of heart disease in women.” To evaluate patient risk, the guidelines incorporate illnesses linked to higher risk of cardiovascular disease in women, including lupus and rheumatoid arthritis, and pregnancy complications such as preeclampsia, gestational diabetes or pregnancy-induced hypertension. Mosca said women with a history of preeclampsia face double the risk of stroke, heart disease and dangerous clotting in veins during the five to 15 years after pregnancy. Essentially, having pregnancy complications can now be considered equivalent to having failed a stress test. “These have not traditionally been top of mind as risk factors for heart disease,” she said. “But if your doctor doesn’t bring it up, you should ask if you’re at risk for heart disease because of pregnancy complications or other medical conditions you’ve experienced.” The updated guidelines also emphasize the importance of recognizing racial and ethnic diversity and its impact on cardiovascular disease. For example, hypertension is a particular problem among African-American women and diabetes among Hispanic women. Although putting clinical research into practical, everyday adherence can be challenging, solid scientific evidence is still the basis for many of the guidelines, Mosca said. Some commonly considered therapies for women are noted in the guidelines as lacking strong clinical evidence in their effectiveness for preventing cardiovascular disease and, in fact, may be harmful to some women. Those include the use of hormone replacement therapy, antioxidants and folic acid. The update includes depression screening as part of an overall evaluation of women for cardiovascular risk, because while treating depression has not been shown to directly improve cardiovascular health, depression might affect whether women follow their doctor’s advice. Despite a growing body of clinical evidence to fight heart disease and stroke in women, more is needed, Mosca said. Coronary heart disease death rates in women dropped by two-thirds from 1980 to 2007, due to both effective treatment and risk factor reduction, according to the American Heart Association, but cardiovascular disease still kills about one woman every minute in the United States. In future studies, researchers should look at interventions during specific times throughout a woman’s lifespan ― including puberty, pregnancy and menopause ― to identify risks and determine effective prevention opportunities during those critical times, Mosca said. More cost-effective analyses and clinical trial research with male- and female-specific results are also needed, she said, especially regarding risks posed by preventive therapies.
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Angioplasty for Stroke Associated With Triple Costs, and Unclear Safety and Efficacy

Angioplasty and Stenting of the Carotid Arteries Excluded From Review Angioplasty and stenting of the intra-cranial vessels that supply blood to the brain is predominantly performed at urban teaching hospitals and was associated with nearly triple the cost compared to usual care. However, data on the efficacy and safety of these procedures remains uncertain, according to late-breaking science reported at the American Stroke Association’s International Stroke Conference 2011. Angioplasty and stenting of the carotid arteries was excluded from this review. Authors of the study Intracranial Angioplasty and/or Stent Placement in General Practice analyzed health records from more than 370,000 patients treated from 2005 to 2007 at 1,000 hospitals that participate in the National Inpatient Survey, the largest U.S. all-payer inpatient care database. It is the first large-scale national review of intra-cranial angioplasty and stenting, including outcomes data. “Our findings show these procedures still carry high immediate complication rates and evidence of their efficacy is sketchy and ambiguous,” said Yousef Mohammad, MD, MSc, the study’s lead author, and an associate professor of neurology and director of the Stroke Fellowship Program at Rush University in Chicago. “The three-fold higher hospitalization charges highlight the need for cost-effective application of these procedures,” he said. The study’s primary endpoints were the rate and distribution of intracranial angioplasty in U.S. hospitals. Researchers found:
  • About 80 percent of angioplasty or angioplasty-stent procedures are performed at urban teaching hospitals — possibly due to the need for highly specialized physicians and care units.
  • 158 patients (average age 64, 46 percent female) underwent intracranial angioplasty.
  • 169 patients (average age 62, 50 percent female) had angioplasty plus stenting.
“In addition, we found that the in-hospital mortality in the patients who had these procedures was 16 percent for angioplasty and 4 percent for angioplasty plus stent, which was much higher than the 3.3 percent mortality rate for stroke patients who did not undergo either procedure, even though that group tended to be older,” he said. The increased in-patient mortality rate is beyond what is expected in patients presenting with symptomatic intracranial disease without this procedure, Mohammad said. Moreover, researchers noted that in-hospital charges in patients having these procedures was approximately triple that of patients who did not, costing an average of $89,175 in angioplasty patients and $61,050 in angioplasty-plus-stent patients compared to $24,303 for patients who had neither procedure, he added. Researchers note that a significant proportion of the costs is attributed to the procedure itself. Potential limitations of the study include that the data was gathered from a voluntary registry rather than from a blinded, prospective, randomized trial and was limited to evaluation of short-term data about how patients fared during the time immediately following the procedure, he said. The evolution of intracranial angioplasty and/or stent placement appears similar to the early days of other new procedures, such as the early days of angioplasty in the coronary arteries, Mohammad said. However, he suggests doctors await the results of an ongoing study (SAMMPRIS) that randomize patients to angioplasty with or without stenting versus usual care before recommending this procedure to their patients. In his opinion, the SAMMPRIS trial will determine if the procedure is cost effective.
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Systematic Review Shows DES Outperform BMS in Revascularization of Chronic Total Occlusions

A systematic review of medical evidence has determined drug-eluting stents (DES) outperform bare metal stents (BMS) for revascularization of chronic total occlusions. Researchers found DES reduce restenosis and target revascularization, offering a safe approach with similar adverse events as BMS. Full findings are available in the February 2011 issue of Catheterization and Cardiovascular Interventions. Medical evidence maintains that chronic total occlusions (CTOs), with routinely low procedural success and high incidence of target vessel failure, represent the most challenging type of coronary lesion in interventional cardiology. While specialized guidewires and advanced techniques have improved CTO angioplasty, high rates of restenosis and reocclusion remain a challenge. To determine the performance of DES implantation in CTOs, Emmanouil Brilakis, MD, PhD, FSCAI, of VA North Texas Healthcare System and the University of Texas Southwestern Medical Center in Dallas, and colleagues performed a systematic review of medical literature published in online databases (PubMed, EMBASE, Cochrane Library) and cardiology societies’ websites. The researchers found 17 published studies that reported outcomes for sirolimus- or paclitaxel-eluting stents and BMS implantation for coronary occlusions. “Our findings confirm that treatment of total coronary occlusions with DES is associated with significant reductions in angiographic and clinical restenosis, compared with BMS,” said Dr. Brilakis. Analysis of angiographic outcomes in the studies revealed less restenosis with DES implantation compared to BMS (odds ratio, 0.15). At 6 to 12 months, target lesion and vessel revascularization were also consistently lower among DES-treated patients (odds ratio of 0.13 and 0.18, respectively). In a 19-month follow-up period, the cumulative incidence of mortality, heart attack, or stent thrombosis was similar between DES and BMS in all studies. Dr. Brilakis concluded, “The consistency and magnitude of treatment effect in the individual studies and meta-analysis establish DES as the standard therapy for CTO revascularization. Large, prospective trials that offer additional information on the role of DES in CTO, and determine if second-generation DES could provide even more favorable outcomes are needed.” Currently, three such studies are underway in the Netherlands, Spain, and the United States.
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NIH-Funded Study Finds New Possible Risk Factor for Heart Disease

Abnormal heart rate turbulence is associated with an increased risk of heart disease death in otherwise low-risk older individuals, according to a study funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. This study appears in the Feb. 15 edition of the Journal of Cardiovascular Electrophysiology. Among the nearly 1,300 study participants, heart rate turbulence, which reflects how well the heart reacts to occasional premature contractions, was an even stronger heart disease risk factor than elevated levels of C-reactive protein. CRP is a potential heart disease biomarker that has emerged in recent years. Study participants considered at low risk of heart disease based on traditional risk factors were on average 8 to 9 times more likely to die of heart disease during the roughly 14-year follow-up period if they had abnormal heart rate turbulence values. Traditional risk factors include age, gender, high blood cholesterol, high blood pressure, obesity, diabetes, and smoking. Low-risk individuals with elevated CRP in their blood were about 2.5 times more likely to die than those with normal or low CRP. “These findings suggest that apparently healthy people might be at increased risk of death from cardiovascular disease, and heart rate turbulence may help us identify them,” said Susan B. Shurin, MD, acting director of the NHLBI. “It will be important to see if we can replicate this finding in other populations.” This study followed 1,272 adults aged 65 and older as part of the NHLBI’s Cardiovascular Health Study. Participants were categorized as healthy (no sign of heart disease risk except possibly diabetes), subclinical (some signs of heart disease) or clinical (had a cardiovascular event, such as a heart attack). At the onset, participants underwent 24-hour Holter monitoring. Abnormal heart rate turbulence and CRP levels both appeared to independently correlate with an increased likelihood of dying of heart disease in the group that was categorized as healthy, even after controlling for other risk factors. Abnormal heart rate turbulence, present in about 7 percent of the study participants, also predicted an increased likelihood of heart disease death in the subclinical and clinical groups, though these results were not as pronounced. Heart rate turbulence refers to how smoothly the heart rate returns to normal after a premature ventricular contraction, a fairly common event in which the second portion of a heart beat is triggered too soon. Due to the improper timing between the atrial and ventricular contractions, the ventricles haven’t fully filled with blood and therefore do not push out enough blood to the body. The brain detects this sub-optimal release of blood and instantly increases the heart rate to pump more blood. However, this overcompensation raises blood pressure, causing the brain to react again and lower the heart rate until blood pressure returns to normal. By analyzing the heart’s electrical signals, physicians can measure the magnitude of the initial heart rate jump (turbulence onset) and the speed at which heart rate returns to normal (turbulence slope), and then determine if the heart rate turbulence response is normal or abnormal. “A heart rate turbulence measurement is insightful because it offers a sign of how well the autonomic, or subconscious, nervous system is functioning,” said study author Phyllis K. Stein, PhD, a research associate professor of medicine and director of the Heart Rate Variability Laboratory at Washington University School of Medicine in St. Louis. “If someone’s heart doesn’t react well to these uncoordinated beats that might mean it is not good at reacting to other issues, like sudden stress or severe arrhythmias.” Researchers don’t yet know if abnormal heart rate turbulence can be treated or prevented. In the meantime, said Stein, interest might grow within the medical community in measuring heart rate turbulence in clinical practice. Currently, this type of measurement is not widely available. “This study shows a great potential value for heart rate turbulence in diagnostic settings,” said Robin Boineau, MD, a medical officer in the NHLBI’s Division of Cardiovascular Sciences. “It appears that signs of heart rate turbulence are also generally present a year or more before clinical manifestations of heart disease, indicating that this may be an opportunity for disease prevention in addition to disease prediction.”
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Researchers Confirm Value of Therapeutic Hypothermia After Cardiac Arrest

Mayo Clinic (Rochester, Minn.) researchers confirmed that patients who receive therapeutic hypothermia after resuscitation from cardiac arrest have favorable chances of surviving the event and recovering good functional status. In therapeutic hypothermia, a patient’s body temperature is cooled to 33 degrees Celsius following resuscitation from cardiac arrest, in order to slow the brain’s metabolism and protect the brain against the damage initiated by the lack of blood flow and oxygenation. This study was published in the December 2010 issue of Annals of Neurology. “Therapeutic hypothermia is a neuroprotective strategy. Brain recovery is the main determinant of outcome for patients who survive cardiac resuscitation,” says Alejandro Rabinstein, MD, a Mayo Clinic neurologist. “For a number of years, we have collected information about what determines whether or not a patient is going to wake up after resuscitated cardiac arrest. However, most of this information comes from the time when patients were not treated with therapeutic hypothermia, which now has become the standard of care for many cases of cardiac arrest. We wanted to know whether hypothermia therapy changed what we knew before about how to estimate neurological prognosis in these patients.” In this study, Dr. Rabinstein and his team identified 192 patients, more than 100 of whom were treated with therapeutic hypothermia. Detailed neurologic exams were performed, including electroencephalograms, brain CT scans, and measurement of neuron-specific enolase (NSE). NSE is a substance detected in the blood that provides information about the extent of brain damage. “The results of the study mainly validated what we knew about prognosis following cardiac arrest from non-hypothermia cases. The findings on physical examination on the days following cardiac arrest remain most valuable in estimating the prognosis,” says Dr. Rabinstein. High NSE level in the blood was shown to reliably predict poor outcome after cardiac arrest in patients not treated with hypothermia. However, less is known about the value of this marker in patients who are cooled after the cardiac arrest. Although in this study the presence of elevated levels of NSE was statistically associated with worse outcomes in patients treated with hypothermia, Dr. Rabinstein concluded that the NSE level was not sufficiently reliable to estimate the prognosis in this group of patients, because elevated levels were also seen in some patients who recovered well. Therefore, the NSE level should not be used in isolation to define prognosis in patients treated with hypothermia. “That was a remarkable finding of our study that deserves more attention,” he says. “It’s important for people to know that among patients treated with therapeutic hypothermia following resuscitated cardiac arrest, up to two-thirds of them may go home with good function,” says Dr. Rabinstein. “We are still examining how these patients recover in terms of higher intellectual faculties, but certainly these are results that were not even conceivable prior to the application of therapeutic hypothermia.”
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More Doctors Must Join Nurses, Administrators in Leading Efforts to Improve Patient Safety and Outcomes

Efforts to keep hospital patients safe and continually improve the overall results of health care can’t work unless medical centers figure out a way to get physicians more involved in the process. “Physicians’ training and perspectives on patient care make their contributions to improvement efforts essential,” says Peter J. Pronovost, MD, PhD, a Johns Hopkins patient safety expert and co-author of a commentary published in the Feb. 2 Journal of the American Medical Association. “But the work of improving quality currently rests primarily with hospital administrators and nurses, with physicians taking a peripheral volunteer role, often questioning the wisdom of these efforts.” The major obstacle to recruiting physician leaders to the safety movement, he says, is the failure of medical centers to professionally and financially compensate and reward physicians for spending time on quality-improvement projects. “Such projects take away from the time physicians spend treating patients — and generating revenue,” he says. “What’s needed is a system that would support a portion of a doctor’s time spent managing and standardizing quality of care on a particular unit, in a role similar to what now happens with nurse managers.” Pronovost, a professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine, and Jill A. Marsteller, an assistant professor of health policy and management at the Johns Hopkins Bloomberg School of Public Health, note that studies show little evidence that hospital quality-improvement programs have improved patient outcomes, despite buy-in from top administrators and a push for accountability. “Hospitals will only begin to see progress if they get physicians to not just participate more, but to assume leadership roles in quality improvement,” Pronovost says. Pronovost and Marsteller argue that the root of the problem is the “antiquated” relationship between hospitals and the physicians who practice inside them. “The system we have is that most physicians act almost as independent contractors, autonomously caring for individual patients and essentially renting beds, nursing care and technology from the hospital,” he says. “Physicians often sit on the sidelines, as nurses and executives push for changes they hope will improve patient outcomes.” Doctors need to focus more on not just the individual patients in their care, but also on the hospital’s systems for caring for the patient population as a whole, they say. Pronovost and Marsteller’s prescription is for a formalized “physician management infrastructure” that encourages doctors to design scientifically rigorous quality-improvement interventions, develop performance measures, monitor performance, implement interventions and monitor their impact. Such an infrastructure would include physician leadership training and development, an emphasis on reliable and valid performance measures, and creation of a chain of accountability from the hospital to physician leaders. Pronovost and Marsteller acknowledge that their prescription will cost money that hospitals rarely have. “Hospital margins are thin if they exist at all, and current health reform efforts are focused on paying hospitals less — not rewarding them for improving patient care,” Pronovost says. “This makes it difficult for hospitals to financially support physician quality-improvement leaders, and in many cases hospitals are cutting positions, not adding them.” In the long term, however, Pronovost insists, investment in physician-led quality-improvement efforts will reduce costs and at least pay for themselves. The alternative, he says, is not good for patients or hospitals. “Without monetary support for physician leaders, the quality of care for populations of patients is unlikely to improve,” he says.
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Electronic Stent-Deployment System Wins Student Prize at University of Wisconsin-Madison Event

A system that could widely expand stent treatments for patients with diseased arteries won the top prize and $10,000 in the Schoofs Prize for Creativity, one of a pair of competitions that make up Innovation Days, an event that rewards University of Wisconsin-Madison students for innovative and marketable ideas. For the first time in the competition’s 17-year history, the winning inventor has claimed first place in the Schoofs Prize two years in a row. Mechanical engineering senior Tom Gerold created the MicroMag Stent Deployment System after watching his grandfather struggle with arterial disease. He subsequently learned more about the medical device industry at a summer internship and combined that experience with his engineering coursework to develop a system that could make a significant difference for cardiovascular patients. MicroMag is an electromagnetic system to deploy self-expanding metal stents and retract the catheter that inserts those stents. This system would allow surgeons to place stents in smaller blood vessels than currently is possible. Now, surgeons must physically maneuver catheters, which can cause stents to deploy early or not at all. Gerold’s invention turns stent deployment into a carefully calibrated electronic process that minimizes catheter movement and reduces risk of improper stent deployment. This could significantly increase the number of patients able to receive stent treatment, including those with peripheral artery disease.
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Gender Does Not Increase Risk Of Death From Heart Attack

A study led by the University of Michigan Cardiovascular Center shows being a woman may not increase your risk of dying from treatment for a severe heart attack. U-M researchers and colleagues in the Michigan Cardiovascular Consortium found women who received treatment such as an angioplasty had higher unadjusted in-hospital heart attack deaths. But these differences appear to be related to women’s ages and additional health problems — not gender, says study lead author Elizabeth Jackson, MD, MPH, an assistant professor of internal medicine at the U-M Health System. “When we adjusted for factors such as age and co-morbidities like hypertension and diabetes, women had similar mortality rates at the time of the heart attack as men,” says Jackson. “But women still appear to be more likely to have a bleeding episode in the hospital that requires a transfusion or vascular complications,” she says. The five-year study, published in the American Heart Journal, showed that compared with men, women were older with more comorbidities at the time of treatment. Women account for about one-third of patients who undergo procedures such as percutaneous coronary interventions. Researchers examined the outcomes of 8,771 patients undergoing a procedure for an acute ST-elevation myocardial infarction (STEMI). Patients were part of the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry, a physician-led quality improvement collaborative that is supported by Blue Cross Blue Shield of Michigan and Blue Care Network. Previous investigations using other registries have found women had higher in-hospital mortality rates than men, but recent advancements in treatment changed how doctors care for these patients and the team wanted to re-investigate with more current data, says Jackson. “Overall, there have been tremendous improvements in the care of both men and women who suffer a heart attack, but further research on everyday patients, such as those in the registry, is needed to be able to continue improving our level of care,” says Jackson. The Cardiovascular Consortium, called BMC2, is a collaborative network of physicians at 32 Michigan hospitals. The U-M has been the coordinating center for the statewide BMC2 consortium since 1997. Journal reference: American Heart Journal, doi:10.1016/j.ahj.2010.09.030 Funding: Blue Cross Blue Shield of Michigan
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Newborn Heart Muscle Can Grow Back by Itself

Researchers at the University of Texas (UT) Southwestern Medical Center in Dallas, Texas, have discovered that the mammalian newborn heart can heal itself completely. Researchers, working with mice, found that a portion of the heart removed during the first week after birth grew back wholly and correctly — as if nothing had happened. Dr. Hesham Sadek, assistant professor of internal medicine and senior author of the study available online in the Feb. 25 issue of Science, said, “We found that the heart of newborn mammals can fix itself; it just forgets how as it gets older. The challenge now is to find a way to remind the adult heart how to fix itself again.” Previous research has demonstrated that some lower organisms, such as fish and amphibians, who can regrow fins and tails, can also regrow portions of their hearts after injury. The researchers found that within three weeks of removing 15% of the newborn mouse heart, the heart was able to completely grow back the lost tissue, and as a result looked and functioned just like a normal heart. The researchers believe that cardiomyocytes are a major source of the new cells. They stop beating long enough to divide and provide the heart with fresh cardiomyocytes. Dr. Eric Olson, chairman of molecular biology and co-senior author of the study, said, “The inability of the adult heart to regenerate following injury represents a major barrier in cardiovascular medicine.” Dr. Olson also directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic and Clinical Research in Pediatric Oncology. “This work demonstrates that cardiac regeneration is possible in the mammalian heart during a window of time after birth, but this regenerative ability is then lost. Armed with this knowledge, we can next work to discover methods to reawaken cardiac regeneration in adulthood.” The next step, the researchers said, is to study this brief window when the heart is still capable of regeneration, and to find out how, and why, the heart “turns off” this remarkable ability to regenerate as it grows older.
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New Hypothesis Explains Why Drugs Increase Risk of Heart Attacks and Strokes

Analysis highlights cardiovascular risk of fluid retention New research shows that medications which have raised safety concerns over heart attack and stroke risks may not have gotten approval from the Food and Drug Administration (FDA) if the cardiovascular effects of fluid retention had been better understood. Fluid retention may explain the increased risk of heart attacks and strokes of medications such as Vioxx®, Bextra®, and Avandia®. The research, published in Clinical Hemorheology and Microcirculation, calculates the effects of fluid retention upon the velocity of blood flow and the turbulence of flowing blood. These calculations demonstrate that fluid retention increases the risk of heart attacks and strokes. Since numerous medications cause fluid retention, the paper’s findings have implications to ensure drugs on the market are safe. The pain medications Vioxx and Bextra, and the anti-diabetic medication Avandia, cause fluid retention. Vioxx and Bextra, known as cyclo-oxygenase-2 (COX-2) inhibitors, were withdrawn from the market because of safety concerns over heart attacks and strokes, and Avandia has been suspected in some reports of increasing the risk of heart attacks. The paper’s author, Robert P. Blankfield, MD, MS, clinical professor of family medicine at Case Western Reserve University School of Medicine, and a member of the Department of Family Medicine at University Hospitals Case Medical Center, used several basic cardiovascular and hydraulic equations to demonstrate that fluid retention is detrimental for the cardiovascular system. Fluid retention increases the likelihood that blood will flow in a turbulent manner. Turbulent blood flow accelerates atherosclerosis, thereby increasing the risk of heart attacks and strokes. Many medications cause fluid retention, which raises blood pressure in some, but not all, individuals. Physicians worry about fluid retention if it does raise blood pressure, but are unconcerned when blood pressure is unaffected. “This paper demonstrates that fluid retention is unhealthy because it increases the likelihood that blood will flow in a turbulent manner regardless of whether or not blood pressure is raised. Therefore, drugs that cause the body to retain fluid are dangerous for the cardiovascular system,” says Dr. Blankfield. “If the FDA had been aware of the increased cardiovascular risk that arises from drugs that cause fluid retention, Vioxx, Bextra, and Avandia might never have been approved. These findings might spur the FDA to alter some of its current policies,” he continues. “The calculations in this paper might also help pharmaceutical manufacturers screen drugs for their cardiovascular risk at an early stage in the drug development process.” The cardiovascular safety problems with Avandia have prompted the FDA to require verification of cardiovascular safety for new anti-diabetic medications. It is Dr. Blankfield’s opinion that this response by the FDA does not go far enough. “Based upon the calculations in the manuscript, the FDA ought to require verification of cardiovascular safety for all medications, old as well as new, that cause fluid retention,” says Dr. Blankfield. Several older anti-diabetic medications cause fluid retention, including insulin and sulfonylureas (glyburide, glipizide, glimerperide). The paper suggests it would make more sense to scrutinize these older anti-diabetic medications for cardiovascular safety than to scrutinize newer anti-diabetic medications, such as saxagliptin, that do not cause fluid retention. Additional medications currently on the market that cause fluid retention include the COX-2 inhibitor Celebrex®, non-selective non-steroidal anti-inflammatory drugs (ibuprofen, known as Advil®, Motrin®) and some anti-seizure medications (Neurontin®, Lyrica®, Tegretol®). Fluid retention increases blood pressure in some individuals, increases stroke volume in others, and causes edema. Some blood pressure lowering medications also increase stroke volume and cause edema, but prevent heart attacks and strokes when used to treat hypertension. According to Dr. Blankfield, it would make sense for drug companies to be cautious about bringing drugs to market that cause fluid retention but do not lower blood pressure. He adds that it may be possible to reduce or neutralize the increased cardiovascular risk that occurs as a result of fluid retention simply by using a diuretic. Therefore, patients may be able to safely use medications such as Vioxx, Bextra, and Avandia if they simultaneously use a water pill. The mathematical analysis performed by Dr. Blankfield has implications for public health and safety that extend beyond medications. Because sodium chloride (table salt) causes fluid retention, it likely increases the risk of heart attacks and strokes. Since it is a food additive, it would be appropriate for the FDA to address the danger of consuming sodium chloride. It would be possible to categorize processed foods based upon whether they have a low or high salt content. The FDA could mandate that processed foods with a high salt content be labeled with a simple warning: Based upon the amount of sodium chloride (salt) in this food, eating this product increases the risk of heart attacks and strokes. In summary, if Dr. Blankfield’s mathematical analysis accurately reflects the workings of the cardiovascular system, pharmaceutical manufacturers may be able to identify the cardiovascular risk of drugs by utilizing basic principles of hemodynamics and hydraulics; the FDA may be able to assure the cardiovascular safety of all drugs by mandating that pharmaceutical manufacturers obtain detailed data on those drugs that cause fluid retention but do not lower blood pressure; and for drugs that have beneficial effects but also cause fluid retention, it may be possible for patients to safely use these drugs if they simultaneously use a water pill. The article, “Calculated effect of fluid retention upon velocity of blood flow and turbulence: Implications for atherosclerosis,” by Robert P. Blankfield, MD, MS (doi 10.3233/CH-2010-1369, pages 79–89) is published in Clinical Hemorheology and Microcirculation and can be viewed through this link: http:// iospress.metapress.com/content/717n 533867032rr1/?p=16c4b485a9f541f088dd4737d9b59bcb&pi=0 (shortened link is http://bit.ly/dLKoQD), free of charge.
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