Tag: Internal Medicine (Cardiology)

The minimally invasive implantation of tiny coils into the lungs improves exercise ability, lung function and quality of life for patients with severe emphysema, according to a large international trial presented by researchers at the University of Pittsburgh School of Medicine. The findings were published in the Journal of the American Medical Association and presented today at the American Thoracic Society International Meeting in San Francisco.

“Some patients with advanced emphysema have few treatment options, and this trial significantly furthers our understanding of the potential role of minimally invasive lung volume reduction therapy as an option to improve symptoms,” said lead author Frank Sciurba, M.D., director of the UPMC Pulmonary Function and Exercise Physiology Laboratory, and professor, Division of Pulmonology, Allergy and Critical Care Medicine at Pitt.

Patients with emphysema, a form of chronic obstructive pulmonary disease (COPD), experience an over-inflation of the lungs that limits their ability to breathe deeply, resulting from progressive destruction of the air sacs of their lungs and collapse of the airways. The coils are intended to improve the elastic properties of the lungs to prevent collapse of the airways, allowing patients to exhale more completely, Dr. Sciurba explained.

The study included 315 patients recruited at 26 sites in the U.S. and Europe between December 2012 and November 2015. With over 75 percent of study participants experiencing severe symptoms yet having a pattern of emphysema not allowing them to be candidates for surgery or experimental valve treatment, those patients had few therapeutic options short of lung transplantation.

Participants were randomly assigned to either standard care, which included optimal inhaler medications and pulmonary rehabilitation, or to receive standard care plus bilateral coil insertion placed in the most severely affected lobe of each lung.

The researchers measured how far participants could walk in six minutes, both at baseline and after 12 months of treatment. Patients who received coils showed a modest improvement in walking distance at 12 months, while the usual care group declined in function over the same time period.

After one-year follow-up, the coil group overall was able to walk 15 meters farther than the usual care group in the allotted six minutes. Forty percent of the coil group was able to walk an additional 25 meters more, while only 27 percent of the non-coil group achieved those walking gains.

Forced expiration of air, the most common measure of lung function in emphysema patients, also improved in those receiving coils more so than in those who didn’t receive them.

Patients receiving coils reported dramatic improvement in their quality of life, which is measured by the emphysema-specific St. George’s Respiratory Questionnaire, with 32 percent more patients in the coil group achieving a meaningful level of self-reported improvement over those in the non-coil group.

The benefits of the coils did come at a cost–initially, patients had a significantly higher rate of major complications such as pneumonia and pneumothorax than those in usual treatment group. However, the increased risk of serious adverse events appeared to be short lived. By nine months, there was no difference between the two groups. There also was no difference in the death rate measured at 12 months.

The investigators learned over the course of the study that some of the events initially thought to be pneumonia may in fact be changes in the X-ray due to tension from the coils that may in the long run result in a better patient improvement.

Additional findings by the investigators identified patients who may achieve the greatest benefit from coils. Patients with the greatest degree of lung over-inflation had the greatest improvements in walk distance and symptoms compared to the least over-inflated patients. Also, patients with additional medical issues beyond COPD appeared to improve less.

“Overall, the coils provided a modest improvement in exercise ability and lung function, and a very clinically important improvement in quality of life, but with a higher likelihood of major complications,” Dr. Sciurba said. “This provides an evidence-based choice for symptomatic patients with few options.”

The U.S. Food and Drug Administration (FDA) will now determine whether the coils are ready for widespread use, he added.

UPMC’s Division of Pulmonology, Allergy and Critical Care Medicine has a long history of pioneering treatments for lung disease, beginning with innovations in lung volume reduction surgery in the mid-1990s and continuing with active involvement in clinical trials aimed at providing a less invasive treatment approach. UPMC also is home to a leading lung transplant program.

“This trial represents an extension of a 20-year legacy of UPMC leadership in surgical and bronchoscopic lung volume reduction approaches,” said division chief Rama Mallampalli, M.D.

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https://www.sciencedaily.com/releases/2016/05/160515183719.htm  Original web page at Science Daily

Research has implications for better understanding the relationship between ‘good’ cholesterol function — in addition to level — and heart disease risk.

The generally accepted medical maxim that elevated HDL cholesterol (HDL-C) is “good” has been overturned by a multi-center, international study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania. They show that a certain genetic cause of increased HDL-C may actually be “bad,” noting that a specific mutation in a gene which encodes a cell receptor protein that binds to HDL prevents the receptor from functioning. The mutation causes an increased risk of coronary heart disease even in the presence of elevated levels of HDL-C or “good” cholesterol. Their findings are published this week in Science.

Previous research raised the possibility that HDL might not be quite as protective against heart disease as generally believed by cardiologists, especially after several clinical trials of HDL-raising drugs showed little or no effect. “The thinking about HDL has evolved recently to the concept that it may not directly protect against all heart disease,” said senior author Daniel J. Rader, MD, chair of the department of Genetics. “Our results indicate that some causes of raised HDL actually increase risk for heart disease. This is the first demonstration of a genetic mutation that raises HDL but increases risk of heart disease.”

Rader and his colleagues sequenced the lipid-modifying regions of the genomes of 328 people with markedly elevated HDL (along with a control group with lower HDL) to identify genetic causes of high HDL. One of the genes they focused on was SCARB1, which encodes for Scavenger Receptor B1 (SR-B1), the major receptor for HDL on cell surfaces.

In the course of this sequencing, they identified, for the first time, a person without any SCARB1 function, typified by an extremely high HDL-C level of about 150 mg/dL, whereas the normal level is about 50 mg/dL. The subject had two copies of a SCARB1 mutation called P376L, which the team showed caused a breakdown in HDL receptor function.

Among the many approaches they took, the researchers generated induced pluripotent stem cells (iPSCs) from the SCARB1-deficient person, used them to create liver cells, and showed these new cells had profound reduction in their ability to take up HDL. “This mutation prevents the receptor from getting to the cell surface where it needs to be situated in order to bind and take up HDL,” Rader explained. “This disruption in the receptor’s job is due to mistakes in its folding and processing during protein synthesis.”

Going back to the other sequenced genomes, the researchers were then able to show that persons who carry only one copy of the SCARB1 P376L mutation have significantly higher HDL-C levels. From this, Rader and colleagues had a hunch, based on their knowledge of SCARB1 function and previous studies in mice, that having the SCARB1 P376L mutation, despite raising HDL, might paradoxically increase the risk of heart disease.

Working with other researchers around the world, the Penn team was able to show exactly what they had surmised. “This SCARB1 variant, while rare, is just frequent enough that it allowed us to ask the question about its effect on HDL and heart disease in people with only one copy of the mutation,” Rader said.

The Penn team and their colleagues plan to characterize and test other SCARB1 mutations for their relationship to HDL levels and heart disease. Other genes may also have similar effects. “Eventually we may want to perform genetic testing in persons with high HDL to make sure they don’t have mutations–like this one–that raise HDL but don’t protect against, or may even increase, risk for heart disease,” Rader said. Since the P376L mutation in SCARB1 appears to be specific to people of Ashkenazi Jewish descent, testing in this ethnic group might be particularly important.

Rader suggests that a therapeutic approach to increase the expression or activity of SCARB1 could be a new way to reduce the risk of heart disease even though it would reduce HDL blood levels. “The work demonstrates that the protective effects of HDL are more dependent upon how it functions than merely how much of it is present,” Rader concluded. “We still have a lot to learn about the relationship between HDL function and heart disease risk.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160310143801.htm  Original web page at Science Daily

Long-term data collected on the use of an FDA-approved wireless heart failure monitor shows the treatment cut hospitalizations nearly in half and significantly reduced risk of death in patients. It’s the longest follow-up of hemodynamic monitoring reported, published online by The Lancet.

Dr. William Abraham, director of the Division of Cardiovascular Medicine at The Ohio State University Wexner Medical Center, has devoted 20 years of his career to researching hemodynamic monitoring and was the national co-principle investigator on the study of the CardioMEMS HF System and the long-term analysis.

“The monitor, which is about the size of a paper clip, sits in the pulmonary artery and transmits real-time pressure readings to a secure website where doctors can review them,” Abraham said. “An increase in pressure is an early sign of congestion, so treating these elevations early, before patients get sick, improves lives and keeps people out of the hospital.”

All 347 patients in the long-term analysis had moderate (NYHA Class III) heart failure and were implanted with the device at the beginning. For the first 18 months, doctors treating the control group did not receive pulmonary artery pressure readings and provided standard care based on signs and symptoms of worsening heart failure. Then for an additional 13 months, the doctors had access to the sensor readings and made care decisions based on pulmonary artery pressure readings. That’s when hospitalizations in the control group dropped by 48 percent. Those receiving treatment for the entire 31 months of follow-up also saw a 33 percent reduction in hospitalizations.

“This is a highly significant reduction that further supports the effectiveness of real-time monitoring and proactively managing our patients,” Abraham said. “I believe this treatment will make a dramatic impact in the lives of heart failure patients, and in the costs of managing these patients.”

The Centers for Disease Control and Prevention reports heart failure affects approximately 5 million Americans and costs the nation about $32 billion per year in health care services, medications and missed productivity. The CardioMEMS HF device was FDA approved in May 2014. Ohio State University’s Richard M. Ross Heart Hospital was the first in the nation to implant the device.

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http://www.sciencedaily.com/releases/2015/11/151109110640.htm  Original web page at Science Daily

Researchers at the University of Liverpool’s Institute of Infection and Global Health (IGH) have discovered a common cause of heart damage in patients with sepsis. Sepsis is the most common cause of death in hospitalized critically ill people and affects up to 18 million people world-wide annually.

The electrical and mechanical malfunctions of the heart have been poorly understood in sepsis, with underdeveloped clinical management strategies, as a consequence. This new discovery, however, promises to benefit a high number of patients with heart failure or rhythm abnormalities that complicate sepsis.

The team discovered that nuclear proteins, called histones, induce damage to heart muscle cells when released into the blood circulation following extensive cell damage in sepsis.

Blood levels of histones, however, are robust biomarkers that can predict which patients are more likely to develop heart complications. Dr Yasir Alhamdi, from the University’s Institute of Infection and Global Health, said: “This new discovery has important clinical implications. Firstly, we now provide a much-needed explanation for why cardiac injury markers are high in sepsis.

“Secondly, histone levels in the blood can potentially be used at an early stage to predict which septic patients are at highest risk of developing deadly heart complications. This can improve overall management of patients with sepsis worldwide.” The research team has also developed and tested specific antibodies that can directly neutralise the toxic effects of histones in the blood circulation and found that their use can significantly prevent the development of heart complications in sepsis.

Professor Cheng-Hock Toh, from the University’s Institute of Infection and Global Health, said: “The translational impact to patients with sepsis can extend beyond biomarker prediction of heart complications, to novel targeted treatment for improved survival. “This discovery could therefore enable us to better stratify patients for more precise and personalised treatment in sepsis.”

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http://www.sciencedaily.com/releases/2015/07/150709103050.htm  Original web page at Science Daily

Doctors’ efforts to battle the dangerous atherosclerotic plaques that build up in our arteries and cause heart attacks and strokes are built on several false beliefs about the fundamental composition and formation of the plaques, new research from the University of Virginia School of Medicine shows. These new discoveries will force researchers to reassess their approaches to developing treatments and discard some of their basic assumptions about atherosclerosis, commonly known as hardening of the arteries.

“The leading cause of death worldwide is complications of atherosclerosis, and the most common end-stage disease is when an atherosclerotic plaque ruptures. If this occurs in one of your large coronary arteries, it’s a catastrophic event,” said Gary K. Owens, PhD, of UVA’s Robert M. Berne Cardiovascular Research Center. “Once a plaque ruptures, it can induce formation of a large clot that can block blood flow to the downstream regions. This is what causes most heart attacks. The clot can also dislodge and cause a stroke if it lodges in a blood vessel in the brain. As such, understanding what controls the stability of plaques is extremely important. ”

Until now, doctors have believed that smooth muscle cells — the cells that help blood vessels contract and dilate — were the good guys in the body’s battle against atherosclerotic plaque. They were thought to migrate from their normal location in the blood vessel wall into the developing atherosclerotic plaque, where they would attempt to wall off the accumulating fats, dying cells and other nasty components of the plaque. The dogma has been that the more smooth muscle cells in that wall — particularly in the innermost layer referred to as the “fibrous cap” — the more stable the plaque is and the less danger it poses.

UVA’s research reveals those notions are woefully incomplete at best. Scientists have grossly misjudged the number of smooth muscle cells inside the plaques, the work shows, suggesting the cells are not just involved in forming a barrier so much as contributing to the plaque itself. “We suspected there was a small number of smooth muscle cells we were failing to identify using the typical immunostaining detection methods. It wasn’t a small number. It was 82 percent,” Owens said. “Eighty-two percent of the smooth muscle cells within advanced atherosclerotic lesions cannot be identified using the typical methodology since the lesion cells down-regulate smooth muscle cell markers. As such, we have grossly underestimated how many smooth muscle cells are in the lesion.”

Suddenly, the role of smooth muscle cells is much more complex, much less black-and-white. Are they good or bad? Should treatments try to encourage more? It’s no longer that simple, and the problem is made all the more complicated by the fact that some smooth muscle cells were being misidentified as immune cells called macrophages, while some macrophage-derived cells were masquerading as smooth muscle cells. It’s very confusing, even for scientists, and it has led to what Owens called “complete ambiguity as to which cell is which within the lesion.” (The research also shows other subsets of smooth muscle cells were transitioning to cells resembling stem cells and myofibroblasts.)

Researcher Laura S. Shankman, a PhD student in the Owens lab, was able to overcome the limitations of the traditional methodology for detecting smooth muscle cells in the plaque. Her approach was to genetically tag smooth muscle cells early in their development, so she could follow them and their descendants even if they changed their stripes. “This allowed us to mark smooth muscle cells when we were confident that they were actually smooth muscle cells,” she said. “Then we let the atherosclerosis develop and progress [in mice] in order to see where those cells were later in disease.”

Further, Shankman identified a key gene, Klf4, that appears to regulate these transitions of smooth muscle cells. Remarkably, when she genetically knocked out Klf4 selectively in smooth muscle cells, the atherosclerotic plaques shrank dramatically and exhibited features indicating they were more stable — the ideal therapeutic goal for treating the disease in people. Of major interest, loss of Klf4 in smooth muscle cells did not reduce the number of these cells in lesions but resulted in them undergoing transitions in their functional properties that appear to be beneficial in disease pathogenesis. That is, it switched them from being “bad” guys to “good” guys.

Taken together, Shankman’s findings raise many critical questions about previous studies built on techniques that failed to assess the composition of the lesions accurately. Moreover, her studies are the first to indicate that therapies targeted at controlling the properties of smooth muscle cells within lesions may be highly effective in treating a disease that is the leading cause of death worldwide. The discoveries have been outlined in a paper published online by the journal Nature Medicine.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/07/150706123730.htm  Original web page at Science Daily

Patients with atrial fibrillation who stopped taking blood thinners before they had elective surgery had no higher risk of developing blood clots and less risk of major bleeding compared to patients who were given a “bridge” therapy, according to research led by Duke Medicine.

The findings add much-needed clarity to inconsistent practice guidelines that annually affect an estimated 250,000 patients with atrial fibrillation/flutter who take the blood thinner warfarin. The Duke-led study was presented June 22, 2015, at the International Society on Thrombosis and Haemostasis meeting and published in The New England Journal of Medicine.

Currently, atrial fibrillation patients are typically told to halt their warfarin for five days before and after they undergo an elective procedure, because it can cause dangerous bleeding and slow healing. After the procedure and resuming warfarin, it may take five or more days before the blood thinner reaches its effective target therapeutic level. To continue protecting them from blood clots during this intermission, many doctors prescribe a low-molecular weight heparin, a faster-acting blood thinner in what is known as a “bridge” therapy.

“Bridging has been controversial because there has been a lack of data demonstrating that it’s necessary, so people don’t know what to do,” said senior author Thomas L. Ortel, M.D., Ph.D, chief of the Division of Hematology at Duke the principal investigator of the Clinical Coordinating Center for the study. The study’s Statistical Data Coordinating Center, led by Vic Hasselblad, Ph.D., and the Clinical Coordinating Center were both based at the Duke Clinical Research Institute.

“You can go to five different doctors, and some will bridge and others won’t — it just depends on what they feel they can safely do,” Ortel said. “This trial gives a firm answer to that question.”

The study, called BRIDGE, enrolled 1,884 patients with atrial fibrillation and atrial flutter, with roughly half getting the bridge therapy (dalteparin) and the other half receiving a placebo while halting their warfarin for up to 13 days around their elective surgeries. Patients were followed for up to 37 days after their procedures.

Among patients who stopped all blood thinners, the incidence of arterial blood clot was 0.4 percent, compared to 0.3 percent for patients who received the bridge therapy. Major bleeding events were significantly less common among the non-bridging group, occurring in 1.3 percent of patients who received no blood thinners, compared to 3.2 percent of those in the bridging group.

“Bridging does not improve the outcome for stroke prevention, but increases the risk of major bleeding complications,” Ortel said. “That’s the counter balance — we’re not doing patients any good, and we are potentially hurting them.”

Ortel noted that the findings are specific to patients with atrial fibrillation who take warfarin, and should not be generalized to other types of patients on the blood thinner. He said the findings also do not cover newer blood thinners. But the results will be taken into consideration by the organizations that develop guidelines for doctors on managing atrial fibrillation patients who plan to undergo a procedure or surgery.

“This is the first study to provide high-quality clinical trial data demonstrating that for patients with atrial fibrillation who need a procedure and who need to come off warfarin, they can simply stop and restart,” Ortel said. “They do not need to be bridged.”

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http://www.sciencedaily.com/releases/2015/06/150622092350.htm  Original web page at Science Daily

Thin, lightweight and flexible materials developed by researchers at Florida Atlantic University, Stanford University and Harvard University, integrate cellulose paper and flexible polyester films as new diagnostic tools to detect bioagents in whole blood, serum and peritoneal fluid. In much the same way that glucometers and pregnancy tests have revolutionized in-home diagnostic testing, researchers from Florida Atlantic University and collaborators have identified a new biosensing platform that could be used to remotely detect and determine treatment options for HIV, E-coli, Staphylococcus aureas and other bacteria. Using a drop of blood from a fingerprick, this novel biosensing platform provides clinically relevant specificity, sensitivity and detection of pathogens from whole blood and plasma.

The thin, lightweight and flexible materials developed by these researchers can be fabricated and operated without the need for expensive infrastructure and skilled personnel, potentially solving real-world healthcare problems for both developed and developing countries. Using this technology, they also have developed a phone app that could detect bacteria and disease in the blood using images from a cellphone that could easily be analyzed from anywhere in the world. In the article, the researchers address the limitations of current paper and flexible material-based platforms and explain how they have integrated cellulose paper and flexible polyester films as new diagnostic tools to detect bioagents in whole blood, serum and peritoneal fluid. They employed three different paper and flexible material-based platforms incorporated with electrical and optical sensing modalities. They were able to demonstrate how these new materials can be widely applied to a variety of settings including medical diagnostic and biology laboratories.

Using paper and flexible substrates as materials for biosensors, Asghar and his colleagues have identified a new rapid and cost-effective way to diagnose diseases and monitor treatment in point-of-care settings. They have been able to show how their new platforms are uniquely able to isolate and detect multiple biotargets selectively, sensitively, and repeatedly from diverse biological mediums using antibodies. “There is a dire need for robust, portable, disposable and inexpensive biosensing platforms for clinical care, especially in developing countries with limited resources,” said Asghar. Existing paper and flexible material-based platforms use colorimetric, fluorometric and electrochemical approaches that require complex labeling steps to amplify their signal, are very costly to fabricate and also require expensive equipment and infrastructure.

“The future of diagnostics and health monitoring will have potentially cell-phone based or portable readers sipping saliva or blood and continuously monitoring human health taking it way beyond where we are with counting steps today,” said Demirci, who is the corresponding author. Asghar notes that because their materials are easy to make, easy to use, and can easily and safely be disposed by burning, they provide appealing strategies for developing affordable tools that have broad applications such as drug development, food safety, environmental monitoring, veterinary medicine and diagnosing infectious diseases in developing countries. “Our paper microchip technologies can potentially have a significant impact on infectious diseases management in low- and middle-income countries where there is limited laboratory infrastructure,” said Shafiee. Demirci notes that these platforms could potentially be adapted and tailored to detect other pathogens and biotargets with well-known biomarkers.

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http://www.sciencedaily.com/releases/2015/04/150402092042.htm  Original web page at Science Daily

Despite the advent of a new generation of stents, patients with multiple narrowed arteries in the heart who received coronary artery bypass grafting fared better than those whose arteries were opened with balloon angioplasty and stents in a study presented at the American College of Cardiology’s 64th Annual Scientific Session. The findings echo past studies, which have shown patients with multiple narrowed arteries have better outcomes with coronary artery bypass grafting, also known as CABG or heart bypass surgery, than with angioplasty, also known as percutaneous coronary intervention or PCI, a less-invasive option in which a stent is inserted to hold the arteries open.

In the new study, patients receiving angioplasty with the new stents had a 47 percent higher risk of one of the outcomes identified as a primary endpoint in the study: death, heart attack and subsequent procedure to clear blocked arteries, as compared to patients who received bypass. In bypass surgery, a vein or artery from elsewhere in the body is grafted onto a narrowed coronary artery to allow blood to flow to the heart more freely. The study reinforces current guidelines, which recommend bypass surgery for treating patients with substantial narrowing in multiple arteries, a condition known as multivessel coronary artery disease. “Based on our data, CABG is still the preferred option for multivessel disease,” said Seung-Jung Park, M.D., a cardiologist at Asan Medical Center in Seoul, South Korea, and the study’s lead author. “We had thought that previous trials may have been limited by their use of first-generation drug-eluting stents, but these results show CABG still leads to better outcomes.”

The study, called the Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease (BEST) trial, is one of only two randomized controlled trials to compare bypass to angioplasty since the introduction of everolimus-eluting stents, a new generation of drug-eluting stent. These stents emit medication to prevent blood clots and have been shown to be more effective at keeping arteries open. The trial’s findings align with those from the previous study, called Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX). The study included 880 patients treated at 27 hospitals in four countries. All patients had multivessel coronary artery disease and were determined to be equally appropriate candidates for either angioplasty or bypass. Half of the patients were randomly assigned to receive angioplasty with everolimus-eluting stent and half received bypass surgery. Patients were tracked for an average of more than 4.5 years. “During this relatively long-term follow-up, angioplasty was associated with a significant increase in the incidence of the death, myocardial infarction and target vessel revascularization, a difference that was mainly attributed to the higher rate of target-vessel revascularization in the angioplasty group,” Park said.

Death, heart attack or a subsequent procedure to clear blocked arteries occurred in 15 percent of patients in the angioplasty group and 11 percent of patients in the bypass group. In addition, the researchers found patients receiving angioplasty were twice as likely to need repeat revascularization and more than 1.8 times as likely to have a heart attack as patients who received bypass. The study was terminated earlier than planned, limiting its statistical power to detect differences in individual outcomes instead of only composite outcomes. The early termination was due to slow enrollment, thought to be a consequence of the rapid spread and increased appeal of a new angioplasty technique called fractional flow reserve during the later part of the study enrollment period. The angioplasty procedures in the BEST and SYNTAX studies were guided by the medical imaging technique angiography. Fractional flow reserve, by contrast, allows surgeons to more precisely assess the condition of the arteries based on the pressure of blood as it flows through them and has been associated with better outcomes for angioplasty. A new study is currently underway to compare outcomes from bypass to angioplasty using fractional flow reserve in patients with multivessel coronary artery disease. Because it is a more invasive procedure, heart bypass is generally recommended only for patients with higher-risk narrowing in two or more arteries. Angioplasty is preferred for patients with lower-risk narrowing in one or two arteries.

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http://www.sciencedaily.com/releases/2015/03/150316135610.htm  Original web page at Science Daily