Corkscrew-like flow of blood in left atrium may lower risk of stroke
Using specialized CT scans of a healthy heart and one with heart disease, a team of Johns Hopkins cardiologists and biomedical engineers say they’ve created computer models of the “shape” of blood flow through the heart’s upper left chamber that someday may help predict stroke risk.
Specifically, their computer visualizations found that blood in the diseased heart failed to flow in corkscrew-like “eddies” that most effectively moved blood out of the left atrium in the healthy heart. “It showed us exactly how this motion would increase the risk of developing a blood clot,” says Hiroshi Ashikaga, M.D., Ph.D., assistant professor of medicine and member of the Heart and Vascular Institute at the Johns Hopkins University School of Medicine.
The researchers say the same fluid motion analysis used in their two-heart proof-of-concept study may one day offer an accurate way to predict stroke risk in people with heart disease marked by enlargement and weakness of the cardiac muscle.
A description of the study and its results was published in the November 2017 print issue of Annals of Biomedical Engineering.
“By looking at blood flow through the atrium, we think we can accurately assess stroke risk better than such risk factors as heart size and pumping strength,” says Ashikaga. “Our study fills in a missing diagnostic link between heart function and fluid motion in our understanding of how each can affect stroke risk.”
Before this study, Ashikaga notes, researchers knew that enlargement of the heart, particularly the left upper chamber, was linked to increased stroke risk, particularly in people with atrial fibrillation.
The new study, Ashikaga says, sheds significant light on just how an enlarged and “floppy” atrium led to blood clot formation.
Using CT scans of a healthy heart and an enlarged heart to create blood flow models, the researchers were able to visualise the blood flow. In the healthy heart, the researchers saw that the blood flow formed into tight, corkscrew-like motions that circled around into doughnut formations, known as vortexes. The researchers say the vortexes helped move the blood efficiently through the atrium quicker and with less contact with the atrium’s surface tissue.
The diseased heart they chose to examine was enlarged due to overuse, muscle fatigue and scarring, all of which can promote atrial fibrillation.
In the enlarged heart, the researchers noticed that at the top of the atrium, the blood never fully forms the corkscrews that loop around into vortexes. Instead, by the time the blood reaches the bottom of the atrium, it seems to be falling in “sheets” that coat the surface of the heart.
“As the blood comes in contact with the atrium’s surface, it slows down due to shearing forces similar to friction, and this appears to prevent the blood from exiting the chamber as smoothly as it might,” says Ashikaga. “The slower the blood moves and the more contact it has with the atrium, the more risk there is for a clot to form.”
Ashikaga says his team is currently conducting a larger long-term study looking at the blood flow of many more people with normal and ailing hearts, and monitoring the incidence of stroke and other signs of blood clots over time.
Paradigm shift: Antibodies capable of activating nerves, serve as messengers
Antibodies are able to activate human nerve cells within milliseconds and hence modify their function. This is the surprising conclusion of a study carried out at Human Biology at the Technical University of Munich (TUM). This knowledge improves our understanding of illnesses that accompany certain types of cancer, above all severe intestinal malfunctions.
Functional disorders in organs that manifest in conjunction with tumours are called paraneoplastic syndromes. These syndromes are not caused by the primary tumour itself, but are instead frequently a result of the body’s autoimmune reaction. In such cases, a person’s own antibodies turn against their own cells and attack them.
One of these functional disorders is paralysis of the intestinal tract, for example intestinal pseudoobstruction. It makes it difficult for patients to obtain the nutrients and calories they require from their diet. The so-called anti-Hu syndrome is a type of paraneoplastic syndrome often associated with atonic gut and generally occurs in conjunction with small-cell lung cancer. Paraneoplastic syndromes often occur before the tumour is even detected. Hu proteins are usually located in the nucleus of all nerve cells and consist of four family members (HuA, B, C, and D). Because the tumour releases the
Hu protein, the immune system generates antibodies to fight it. Initially, theyserve to defend against the tumour: The greater the concentration of antibodies, the slower the tumour grows. However, these anti-Hu antibodies – named after the first patient in whom these antibodies were discovered in 1985 – also result in an autoimmune reaction with severe gut disorders as an accompanying illness.
Professor Michael Schemann and his colleagues at the Chair for Human Biology at TUM wanted to identify causes for possible nervous function disorders that occur in paraneoplastic syndromes and paralytic intestine. For this purpose, they examined serums from patients with small-cell lung cancer from the Mayo Clinic in Rochester, MN (USA). In a study conducted over a period of ten years, the researchers were able to show for the first time that these patient serums activate human nerve cells within milliseconds without causing neuronal damage. This modifies nerve functions long before the autoimmune reaction damages the nerves.
Working together with the company Euroimmun from Lübeck, the team was even able to identify the factor responsible for this: Normally, nerve cells are activated or inhibited via neurotransmitters that bind to specific structures in the cell membrane (receptors). Surprisingly, it turned out to be an antibody – namely the anti-HuD antibody – which stimulated the nerve cells in the patient serums. What was striking about this finding was the fact that the antibody does not achieve this effect binding to its genuine target protein. “Interestingly, the nerveactivating effect is transmitted via receptors for neurotransmitters,” said Prof Schemann. “These receptors are usually activated by acetylcholine and adenosine triphosphate.” In a nutshell, the antibody more or less mimics the effects of the neurotransmitters acetylcholine and adenosine triphosphate.
The HuD protein typically stabilizes ribonucleic acid (RNA) and has nothing to do with nerve activation. How and where exactly the anti-HuD antibody binds to the receptors continues to remain a black box. However, this newly discovered effect of the anti-HuD-antibody heralds a paradigm shift, according to Prof Schemann, because antibodies are able to activate nerves regardless of antibodyspecific binding structures on the cell membrane.
“Although what we have found will not heal lung cancer itself,” Prof Schemann explained, “it will lead to new clinical understanding and hence hopefully to new therapeutic approaches for related paraneoplastic syndromes such as intestinal pseudoobstruction.”
Just recently, the research group at the Chair for Human Biology, in collaboration with the Charité in Berlin, demonstrated that antibodies are able to activate human nerves. In this case, the functional principle was obvious, as the binding of the antibody to defined structures of a potassium channel modified the excitability of the nerves.
Children of obese parents at risk of developmental delays
Children of obese parents may be at risk for developmental delays, according to a study by researchers at the National Institutes of Health. The investigators found that children of obese mothers were more likely to fail tests of fine motor skill – the ability to control movement of small muscles, such as those in the fingers and hands. Children of obese fathers were more likely to fail measures of social competence, and those born to extremely obese couples also were more likely to fail tests of problem solving ability.
The study, appearing in Pediatrics, was conducted by scientists at the US NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
“The previous U.S. studies in this area have focused on the mothers’ pre- and post-pregnancy weight,” said the study’s first author, Edwina Yeung, Ph.D., an investigator in NICHD’s Division of Intramural Population Health Research. “Our study is one of the few that also includes information about fathers, and our results suggest that dad’s weight also has significant influence on child development.”
In the study, authors reviewed data collected from the Upstate KIDS study, which originally sought to determine if fertility treatments could affect child development from birth through age 3. More than 5,000 women enrolled in the study roughly 4 months after giving birth in New York State between 2008 and 2010. To assess development, parents completed the Ages and Stages Questionnaire after performing a series of activities with their children. The test isn’t used to diagnose specific disabilities, but serves as a screen for potential problems, so that children can be referred for further testing.
Children in the study were tested at 4 months of age and retested 6 more times through age 3. When they enrolled, mothers also provided information on their health and weight – before and after pregnancy – and the weight of their partners.
Compared to children of normal weight mothers, children of obese mothers were nearly 70% more likely to have failed the test indicator on fine motor skill by age 3. Children of obese fathers were 75% more likely to fail the test’s personal-social domain – an indicator of how well they were able to relate to and interact with others by age 3. Children with two obese parents were nearly three times more likely to fail the test’s problem solving section by age 3.
It is not known why parental obesity might increase children’s risk for developmental delay. The authors note that animal studies indicate that obesity during pregnancy may promote inflammation, which could affect the foetal brain. Less information is available on the potential effects of paternal obesity on child development. The authors added that some studies have indicated that obesity could affect the expression of genes in sperm.
If the link between parental obesity and developmental delays is confirmed, the authors wrote, physicians may need to take parental weight into account whenscreening young children for delays and early interventional services.
Transcaval access for aortic valve replacement in high-risk patients
Researchers at the National Institutes of Health have developed a new, less invasive way to perform transcatheter aortic valve replacement (TAVR), a procedure widely used to treat aortic valve stenosis, a lethal heart condition. The new approach, called transcaval access, will make TAVR more available to high risk patients, especially women, whose femoral arteries are too small or diseased to withstand the standard procedure. The Journal of the American College of Cardiology published the findings.
Aortic valve stenosis involves the narrowing of the heart’s aortic valve which reduces blood flow through the heart. For about 85 percent of patients with this condition, doctors typically perform TAVR through the femoral artery in the leg. But for the other 15%, doctors must find a different access route. The most common alternative routes are through the chest, which requires surgery and are associated with significantly more complications.
Transcaval access, which can be performed in awake patients, involves electrifying a small wire so that it crosses between neighbouring blood vessels in the abdomen. The technique calls for making large holes in both the abdominal aorta and the inferior vena cava, which physicians previously considered dangerous because of the risk of fatal bleeding.
The new method was developed by researchers at the US National, Heart, Lung and Blood Institute (NHLBI) and tested in a trial on 100 patients at 20 hospitals across the United States. Researchers said it proved successful in 99 of the patients.
“This is a seminal study,” said the lead author, cardiologist Adam B. Greenbaum, M.D., co-director of the Henry Ford Hospital Center for Structural Heart Disease, Detroit. “It challenged conventional wisdom, which objected to the idea of safe passage between the vena cava and the aorta. More important, it is the first of many nonsurgical minimally-invasive tissue-crossing, or so-called transmural catheter procedures developed at NIH that can be applied to diverse fields of medicine.”
Robert J. Lederman, M.D., a senior investigator in NHLBI’s Division of Intramural Research who led the study, said researchers developed the method to address a specific clinical need, even though they knew it would be a challenging proposition for most surgeons and physicians to accept. The proposed and counterintuitive mechanism of action is that bleeding from the aorta spontaneously decompresses into a corresponding hole the physician makes in the vein, because the surrounding area behind the peritoneum has higher pressure than the vein.
The results of the research, which were independently confirmed by a committee of outside cardiologists, show the procedure not only has a high success rate, but also an acceptable rate of bleeding and vascular complications, particularly in the high risk patients studied. The study builds on the access technique that Lederman’s NHLBI team developed and first tested in animals in 2012 and first applied with Henry Ford physicians to help patients in 2013. NHLBI and its collaborators are now working to find ways to train more specialists to perform the procedure.
Gastric bypass helps severely obese teenagers maintain weight loss over long term, with side-effects
Gastric bypass surgery helps severely obese teenagers lose weight and keep it off, according to the first long-term follow-up studies of teenagers who had undergone the procedure 5-12 years earlier. However, the two studies, published in The Lancet Diabetes & Endocrinology, show some patients will likely need further surgery to deal with the complications of rapid weight loss or may develop vitamin deficiencies later in life.
Severe obesity is classified as having a BMI of 40 or over. Obesity causes ill health, poor quality of life and cuts life expectancy.
The studies are the first to look at long-term effects of gastric bypass surgery in teenagers. Until now, it has been unclear how successful the surgery is in the long-term and whether it can lead to complications. Despite this thousands of teenagers are offered the surgical treatment each year.
Both papers showed that gastric bypass dramatically reduced the teenagers’ weight and helped them maintain weight loss over more than five years of followup. However, the surgery was associated with the development of vitamin D and B12 deficiencies and mild anaemia, and some of those who had a bypass needed further surgery to deal with complications. While the surgery resulted in dramatic weight loss and BMI reductions, many of the teenagers remained obese, meaning that earlier intervention may be needed coupled with lifestyle changes such as diet and exercise.
In the first paper, researchers studied 58 American teenagers aged between 13 and 21 who were severely obese and had a gastric bypass.
Average BMI was reduced from 59 before surgery to 36 a year after surgery. Eight years later, average BMI was 42, equivalent to a loss of 50 kilos per person or a 30% weight reduction. Although the weight loss was significant, almost twothirds of cases (63%, 36/57) remained very obese (BMI over 35) and only one person became a normal weight (BMI 18.5-25) at follow-up.
The number of teenagers with diabetes dropped from 16% to 2%, those with high cholesterol reduced from 86% to 38%, while the number with high blood pressure decreased from 47% to 16% as a result of the surgery. However, some had low levels of vitamin D (78%, 39/50), B12 (16%, 8/50) and mild anaemia (46%, 25/54), which could be a result of lower food consumption or impaired gut absorption.
Given the long-term weight loss and health benefits that result from the surgery, the researchers note that these benefits outweigh the small and manageable risk of nutritional deficiencies.
“Weight loss is crucial for severely obese patients who face poor health and shorter lifespans,” said lead author Dr Thomas Inge, Cincinnati Children’s Hospital Medical Center, USA. “These two manuscripts clearly document long-term benefits of adolescent bariatric treatment, but also highlight several nutritional risks. Now it is important to focus on delivery of the substantial health advantages of surgery while minimizing these risks. Since there are currently two effective bariatric procedures, namely gastric bypass and vertical sleeve gastrectomy, we are currently examining the outcomes of both procedures to determine what is best for adolescents.”
The second study included 81 obese teenagers (average BMI 45) and 81 adults (average BMI 43) in Sweden who had a gastric bypass and 80 teenagers who did not have surgery.
Five years after surgery, the teenagers and adults who had a gastric bypass had a reduced BMI (by 13 points for teenagers, a weight reduction of 28%; 12 points for adults), whereas teenagers who did not have surgery had an increased BMI (by three points from 42 to 45).
Of the teenagers who underwent the gastric bypass, a quarter (25%, 20/81) had further surgery to treat complications from the bypass or as a result of rapid weight loss, including bowel blockage (11 cases) and gallstones (nine cases).
Despite the additional care and resources needed to offer the surgery, overall, the cost of prescriptions for teenagers who had surgery did not differ (US$2317 and $2701). In addition, a quarter of those in the control group (20 of 80) went on to have a gastric bypass as an adult during the study follow-up.
“Gastric bypass results in substantial weight loss as well as cutting heart and metabolic problems and improving quality of life into the long-term for severely obese teenagers. While some patients may face complications, those given non-surgical treatment often continue to put on weight, putting them at higher risk of poor health throughout life,” said lead author Dr Torsten Olbers, University of Gothenburg, Sahlgrenska University Hospital, Sweden. “To reduce risk of complication it’s important that gastric bypass for teenagers is done in centres that can provide the full care needed and long-term follow-up and support.”
Researchers show how emotional stress is associated with cardiovascular disease
Heightened activity in the amygdala – a region of the brain involved in stress – is associated with a greater risk of heart disease and stroke, according to a study published in The Lancet that provides new insights into the possible mechanism by which stress can lead to cardiovascular disease in humans.
While more research and larger studies are needed to confirm the mechanism, the researchers suggest that these findings could eventually lead to new ways to target and treat stress-related cardiovascular risk.
Smoking, high blood pressure and diabetes are well-known risk factors for cardiovascular disease and chronic psychosocial stress could also be a risk factor.
Previously, animal studies identified a link between stress and higher activity in the bone marrow and arteries, but it has remained unclear whether this also applies to humans. Other research has also shown that the amygdala is more active in people with post-traumatic stress disorder (PTSD), anxiety and depression, but before this study no research had identified the region of the brain that links stress to the risk of heart attack and stroke.
In this study, 293 patients were given a combined PET/CT scan to record their brain, bone marrow and spleen activity and inflammation of their arteries. The patients were then tracked for an average of 3.7 years to see if they developed cardiovascular disease. In this time 22 patients had cardiovascular events including heart attack, angina, heart failure, stroke and peripheral arterial disease.
Those with higher amygdala activity had a greater risk of subsequent cardiovascular disease and developed problems sooner than those with lower activity.
The researchers also found that the heightened activity in the amygdala was linked to increased bone marrow activity and inflammation in the arteries, and suggest that this may cause the increased cardiovascular risk. The authors suggest a possible biological mechanism, whereby the amygdala signals to the bone marrow to produce extra white blood cells, which in turn act on the arteries causing them to develop plaques and become inflamed, which can cause heart attack and stroke.
In a small sub-study, 13 patients who had a history of PTSD also had their stress levels assessed by a psychologist, underwent a PET scan and had their levels of C-reactive protein – a protein that indicates levels of inflammation in the body – measured. Those who reported the highest levels of stress had the highest levels of amygdala activity along with more signs of inflammation in their blood and the walls of their arteries.
“Our results provide a unique insight into how stress may lead to cardiovascular disease. This raises the possibility that reducing stress could produce benefits that extend beyond an improved sense of psychological wellbeing,” said lead author Dr Ahmed Tawakol, Massachusetts General Hospital and Harvard Medical School, USA. “Eventually, chronic stress could be treated as an important risk factor for cardiovascular disease, which is routinely screened for and effectively managed like other major cardiovascular disease risk factors.”
The researchers note that the activity seen in the amygdala may contribute to heart disease through additional mechanisms, since the extra white blood cell production and inflammation in the arteries do not account for the full link. They also say that more research is needed to confirm that stress causes this chain of events as the study was relatively small.
|Date of upload: 14th Mar 2017|
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