Peng Zheng shows off the heart of the blood test, chip with a groundbreaking nanostructured surface on which blood is tested. Image: Will Kirk / Johns Hopkins University
With heart attacks, every second counts. A newly developed blood test on a chip diagnoses them in minutes rather than hours and could be adapted as a tool for first responders and people at home.
“Heart attacks require immediate medical intervention in order to improve patient outcomes, but while early diagnosis is critical, it can also be very challenging – and near impossible outside of a clinical setting,” said lead author Peng Zheng, an assistant research scientist at Johns Hopkins University. “We were able to invent a new technology that can quickly and accurately establish if someone is having a heart attack.”
The proof-of-concept work, which can be modified to detect infectious diseases and cancer biomarkers, is described in Advanced Science.
Zheng and senior author Ishan Barman develop diagnostic tools through biophotonics, using laser light to detect biomarkers, which are bodily responses to conditions including disease. Here they used the technology to find the earliest signs in the blood that someone was having a heart attack. Heart attacks remain one of the trickiest conditions to diagnose, with symptoms that vary widely and biological signals that can be subtle and easy to miss in the early stages of an attack, when medical intervention can do the most good.
Will be like ‘ Star Trek tricorder’
People suspected of having heart attacks typically are given a combination of tests to confirm the diagnosis – usually starting with electrocardiograms to measure the electrical activity of the heart, a procedure that takes about five minutes, and blood tests to detect the hallmarks of a heart attack, where lab work can take at least an hour and often has to be repeated.
The stand-alone blood test the team created provides results in five to seven minutes. It’s also more accurate and more affordable than current methods, the researchers say.
Though created for speedy diagnostic work in a clinical setting, the test could be adapted as a hand-held tool that first responders could use in the field, or that people might even be able to use themselves at home.
“We’re talking about speed, we’re talking about accuracy, and we’re talking of the ability to perform measurements outside of a hospital,” said Barman, a bioengineer in JHU’s Department of Mechanical Engineering. “In the future we hope this could be made into a hand-held instrument like a Star Trek tricorder, where you have a drop of blood and then, voilà, in a few seconds you have detection.”
The heart of the invention is a tiny chip with a groundbreaking nanostructured surface on which blood is tested. The chip’s “metasurface” enhances electric and magnetic signals during Raman spectroscopy analysis, making heart attack biomarkers visible in seconds, even in ultra-low concentrations. The tool is sensitive enough to flag heart attack biomarkers that might not be detected at all with current tests, or not detected until much later in an attack.
Though designed to diagnose heart attacks, the tool could be adapted to detect cancer and infectious diseases, the researchers say.
“There is enormous commercial potential,” Barman said. “There’s nothing that limits this platform technology.”
Next the team plans to refine the blood test and explore larger clinical trials.
Right side heart failure. Credit: Scientific Animations CC4.0
A new study from Washington University School of Medicine in St. Louis suggests that a type of immunotherapy also may be an effective treatment strategy for heart failure by using an FDA-approved drug to block the signalling protein IL-1 beta. The study is published in Nature.
After a heart attack, viral infection or other injury to the heart, scar tissue often forms in the heart muscle, where it interferes with the heart’s normal contractions and plays a leading role in heart failure, a chronic condition which can only be slowed, not cured.
Studying human tissue samples as part of the new study, the researchers identified a type of fibroblast cell in the heart as the main culprit responsible for the formation of scar tissue in heart failure. To see if they could prevent scar formation, the scientists turned to mouse models of heart failure that have the very same type of fibroblasts. They used a therapeutic monoclonal antibody that blocks the formation of this harmful type of fibroblast, and succeeded in reducing the formation of scar tissue and improving heart function in the mice.
“After scar tissue forms in the heart, its ability to recover is dramatically impaired or impossible,” said cardiologist and senior author Kory Lavine, MD, PhD, a professor of medicine in the Cardiovascular Division at WashU Medicine. “Heart failure is a growing problem in the US and globally, affecting millions of people. Current treatments can help relieve symptoms and slow the progression, but there is a tremendous need for better therapies that actually stop the disease process and prevent the formation of new scar tissue that causes a loss of heart function. We are hopeful our study will lead to clinical trials investigating this immunotherapy strategy in heart failure patients.”
Fibroblasts have many roles in the heart, and parsing out the differences between various populations of these cells has been challenging. Some types of fibroblasts support the heart’s structural integrity and maintain good blood flow through the heart’s blood vessels, while others are responsible for driving inflammation and the development of scar tissue. Only recently, with the wide availability of the most advanced single cell sequencing technologies, could scientists peg which groups of cells are which.
“These various types of fibroblasts highlight newly recognised opportunities to craft treatment strategies that specifically block the type of fibroblasts that promote scarring and protect fibroblasts that maintain the structure of the heart, so the heart doesn’t rupture,” Lavine said. “Our research suggests that the fibroblasts that promote scarring in the injured heart are very similar to fibroblasts associated with cancer and other inflammatory processes. This opens the door to immunotherapies that potentially can stop the inflammation and resulting scar tissue.”
The research team, co-led by Junedh Amrute, a graduate student in Lavine’s lab, used genetic methods to demonstrate that a signaling molecule called IL-1 beta was important in a chain of events driving fibroblasts to create scar tissue in heart failure. With that in mind, they tested a mouse monoclonal antibody that blocks IL-1 beta and found beneficial effects in the mouse hearts. The mouse monoclonal antibody was provided by Amgen, whose scientists were also co-authors of the study. Monoclonal antibodies are proteins manufactured in the lab that modulate the immune system. The treatment reduced the formation of scar tissue and improved the pumping capacity of the mouse hearts, as measured on an echocardiogram.
At least two FDA-approved monoclonal antibodies, canakinumab and rilonacept, can block IL-1 signalling. These immunotherapies are approved to treat inflammatory disorders such as juvenile idiopathic arthritis and recurrent pericarditis, which is inflammation of the sac surrounding the heart.
One of these antibodies also has been evaluated in a clinical trial for atherosclerosis, a buildup of plaque that hardens the arteries. The trial, called CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), showed a benefit for study participants with atherosclerosis.
“Even though this trial was not designed to test this treatment in heart failure, there are hints in the data that the monoclonal antibody might be beneficial for patients with heart failure,” Lavine said. “Secondary analyses of the data from this trial showed that the treatment was associated with a sizable reduction in heart failure admissions compared with standard care. Our new study may help explain why.”
Even so, the IL-1 antibody used in the CANTOS study had some side effects, such as increased risk of infection, that could perhaps be reduced with a more targeted antibody that specifically blocks IL-1 signaling in cardiac fibroblasts, according to the researchers.
“We are hopeful that the combination of all of this evidence, including our work on the IL-1 beta pathway, will lead to the design of a clinical trial to specifically test the role of targeted immunotherapy in heart failure patients,” Lavine said.
Updated clinical recommendations, including lifestyle changes, prevention strategies and treatment options, to reduce the risk of a first stroke outlined in a new guideline from the American Stroke Association
Credit: American Heart Association
Healthy lifestyle behaviours, such as good nutrition, smoking cessation and being physically active, along with routine health screenings and managing risk factors for cardiovascular disease and stroke with medication, can help prevent individuals from having a first stroke. Screening for stroke risk and educating people on how to lower their chances of having a stroke ideally begin with their primary care professional and include evidence-based recommendations, according to a new clinical guideline from the American Stroke Association, and published in the journal Stroke.
“The most effective way to reduce the occurrence of a stroke and stroke-related death is to prevent the first stroke – referred to as primary prevention,” said Chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, professor and vice chair of research in the department of neurology at Wake Forest University School of Medicine. “Some populations have an elevated risk of stroke, whether it be due to genetics, lifestyle, biological factors and/or social determinants of health, and in some cases, people do not receive appropriate screening to identify their risk.”
The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 version and is a resource for clinicians in implementing a variety of prevention strategies for individuals with no prior history of stroke. The new guideline provides evidence-based recommendations for strategies to support brain health and prevent stroke throughout a person’s lifespan by improving healthy lifestyle behaviours and getting preventive care.
“This guideline is important because new discoveries have been made since the last update 10 years ago. Understanding which people are at increased risk of a first stroke and providing support to preserve heart and brain health can help prevent a first stroke,” said Bushnell.
Key stroke prevention recommendations include regular health screenings, identifying risk factors, lifestyle interventions and medications, when indicated.
Identifying and managing risk factors
Unidentified and unmanaged cardiovascular disease risk factors can cause damage to arteries, the brain and the heart years before cardiovascular disease and stroke occur. Primary care health professionals should promote brain health for patients through stroke prevention education, screenings and addressing risk factors from birth to old age.
Modifiable risk factors for stroke, such as high blood pressure, overweight and obesity, elevated cholesterol and elevated blood sugar, can be identified with physical exams and blood tests. These conditions should be addressed with healthy lifestyle and behavioural changes and may include medications for select patients. Antihypertensive medications to reduce blood pressure and statin medications to lower cholesterol can help to reduce the risk of first stroke in adults with increased cardiovascular disease risk and those receiving CVD care. A new recommendation is consideration of glucagon-like protein-1 (GLP-1) receptor agonist medications, which are FDA-approved to reduce the risk of cardiovascular disease in people with overweight or obesity and/or Type 2 diabetes.
Healthy lifestyle behaviours
The most common, treatable lifestyle behaviours that can help reduce stroke risk are detailed in the Association’s Life’s Essential 8 cardiovascular health metrics. They include healthy nutrition, regular physical activity, avoiding tobacco, healthy sleep and weight, controlling cholesterol, and managing blood pressure and blood sugar. The guideline recommends that adults with no prior cardiovascular disease, as well as those with increased risk, follow a Mediterranean dietary pattern. Mediterranean dietary programs have been shown to reduce the risk of stroke, especially when supplemented with nuts and olive oil.
Physical activity is also essential for stroke risk reduction and overall heart health. Physical activity can help to improve important health measures such as blood pressure, cholesterol, inflammatory markers, insulin resistance, endothelial function and weight. The guideline urges health care professionals to routinely screen patients for sedentary behaviour, a confirmed risk factor for stroke, and counsel them to engage in regular physical activity. The Association reinforces the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion’s recommendation that adults get at least 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week of vigorous aerobic activity, or a combination of both, preferably spread throughout the week.
Health equity and stroke risk
New to the guideline is an emphasis on social determinants of health and the impact they have on stroke risk. Social determinants of health are non-medical factors, including education, economic stability, access to care, discrimination, structural racism and neighborhood factors (such as the lack of walkability, lower availability of healthy food and fewer health resources), that contribute to inequities in care and influence overall health. Health care professionals should ensure patient education is available for various educational and language levels, and advocate for their patients by choosing treatments and medications that are effective and affordable.
Health care professionals are also encouraged to connect patients to resources that help address health-related social needs such as food and housing insecurity, refer them to programs that support healthy lifestyle changes and direct them to support programs that may help defray health care costs including medication expenses.
New sex- and gender-specific recommendations
The guideline also includes some new gender- and sex-specific recommendations for women. Health professionals should screen for conditions that can increase a woman’s risk of stroke, including use of oral contraceptives, high blood pressure during pregnancy, other pregnancy complications such as premature birth, endometriosis, premature ovarian failure and early onset menopause. Treatment of elevated blood pressure during pregnancy and within six weeks of delivery is recommended to reduce the risk of maternal intracerebral haemorrhage.
Transgender women and gender-diverse individuals taking oestrogens for gender affirmation may also be at an increased risk of stroke. Evaluation and modification of any existing risk factors are needed to reduce the risk of stroke for these individuals.
“Implementing the recommendations in this guideline would make it possible to significantly reduce the risk of people having a first stroke. Most strategies that we recommend for preventing stroke will also help reduce the risk of dementia, another serious health condition related to vascular issues in the brain,” said Bushnell.
The writing group notes that writing recommendations focused on preventing a first stroke was challenging. There are limitations to some of the evidence that informed the guideline, including that many clinical trials enrolled adults who have already had a cardiovascular event that may include a stroke. The writing group also identified knowledge gaps to help inform topics for future research.
The guideline highlights the need for risk assessment in primary stroke prevention and includes the use of risk prediction tools to estimate risk for atherosclerotic cardiovascular disease so that patients receive timely prevention and treatment strategies. The Association has recently developed a new Predicting Risk of Cardiovascular Disease Events (PREVENT) risk calculator as a screening tool that can help inform preventive treatment decisions. The PREVENT calculator can estimate 10-year and 30-year stroke and heart disease risk in individuals starting at age 30 – a decade earlier than the Pooled Cohort Equations, another CVD risk calculator.
According to the American Stroke Association, learning the warning signs of stroke and preventative measures are the best way to avoid strokes and keep them from happening again. The abbreviation F.A.S.T. – for face drooping, arm weakness, speech difficulty, time to call 911 – is a useful tool to recognise the warning signs of stroke and when to call for help.
This guideline was prepared by the volunteer writing group on behalf of the American Stroke Association and is endorsed by the Preventive Cardiovascular Nurses Association and the Society for Vascular Surgery. The American College of Obstetricians and Gynecologists supports the clinical value of this document as an educational tool.
Since 1990, the American Stroke Association has translated scientific evidence into clinical practice guidelines with recommendations to improve cerebrovascular health. The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke. The Association supports the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts.
Initial prescriptions of benzodiazepines, a class of drugs used to treat anxiety and sleep problems after a stroke may include too many pills for adults ages 65 or older, finds new study in the Stroke journal
Photo by Towfiqu Barbhuiya on Unsplash
Although there has been a slight downward trend in the prescription of benzodiazepines (depressants that relieve anxiety, muscle spasms, produce sedation and reduce seizures) among older adults over the last decade, the rate of first-time prescriptions for these medications after an ischaemic stroke is still sizable, according to research published today in Stroke.
After a stroke, benzodiazepines may be used to calm anxiety and improve sleep, but also have a potential for abuse and addiction. When prescribed to older adults, these medications may increase the risk of falls and broken bones, as well as memory problems, confusion and other harmful effects.
Researchers reviewed data from Medicare claims in the US and analysed 10 years of first-time prescriptions for benzodiazepines among more than 120 000 people, ages 65 and older, who were hospitalised for ischaemic stroke. The rate of benzodiazepine prescriptions during the first three months after stroke were examined, and data were adjusted for race, sex and ethnicity. Then year-to-year prescription patterns were reviewed to identify the number of potentially excessive new benzodiazepine prescriptions given to stroke survivors.
“We reviewed stroke survivors at 90 days after a stroke because that window of time is critical for rehabilitation of motor, speech and cognitive function, as well as mental health. It’s often a very difficult time for patients who experience loss of mobility and independence. Benzodiazepines may inhibit recovery and rehabilitation,” said study co-author Julianne Brooks, MPH, a data analytics manager at the Center for Value-based Healthcare and Sciences at Massachusetts General Brigham in Boston. “For this older age group, guidelines recommend that benzodiazepine prescriptions should be avoided if possible. However, there may be cases where benzodiazepines are prescribed to be used as needed. For example, to treat breakthrough anxiety, a provider may prescribe a few pills and counsel the patient that the medication should only be used as needed. The increased risks of dependence, falls and other harmful effects should be discussed with the patient.”
The study found:
Within 90 days of stroke, 6127 (4.9%) people were started on a benzodiazepine for the first time.
Lorazepam (40%) and alprazolam (33%) were the most-prescribed benzodiazepine medications.
Three-quarters of the first-time benzodiazepine prescriptions were for a supply of over seven days, and more than half of the prescriptions were for a supply between 15 to 30 days.
Prescription rates were higher among women (5.5%) than men (3.8%).
Prescription fill rates were also higher in Hispanic adults (5.8%), though this group was limited by the small number of participants – 1.9% of the overall sample.
Overall, prescription rates were highest in the Southeast (5.1%) and lowest in the Midwest (4%) of the US. “The Southeast region is the stroke belt with a higher rate of strokes, so that could explain some differences in care in that region,” Brooks said.
There was an overall modest nationwide decline of initial prescriptions from 2013 to 2021 of 1.6%.
“We found a pattern of potential oversupply with these initial benzodiazepine prescriptions, which would be enough for patients to become long-term users or possibly addicted. The benzodiazepine prescriptions given under these circumstances may lead to dependence,” Brooks said. “Increased awareness and improved recommendations about the risks of these medications for older stroke survivors are needed.
“Although the overall prescription rate decreased slightly over 10 years, this prescription pattern is still a problem. It’s concerning because older adults are vulnerable to overprescribing and adverse outcomes. We know from previous studies that vulnerable and marginalized populations experience worse outcomes after stroke, so we want to understand the factors that may play a role so we can provide better care,” Brooks said.
The 2019 American Geriatrics Society Beers Criteria maintains a list of medications that health care professionals can reference to safely prescribe medications for adults older than 65. Beers criteria recommends avoiding benzodiazepines in all older adults due to the risk of cognitive impairment, delirium, falls, fractures and motor vehicle crashes.
“Other guidelines also suggest behavioural interventions such as cognitive behaviour therapy for insomnia, antidepressant medications for anxiety disorders and trying non-pharmaceutical interventions first,” Brooks said.
Researchers said more studies are needed to understand if there is a safe level for prescribing benzodiazepines that may be most appropriate for older adults. The main limitation was that this study used a large, national dataset that did not include information about why benzodiazepines were prescribed.
An analysis of data in the UK Biobank has found that COVID infection may increase the risk of myocardial infarction (MI), stroke and death from any cause for up to three years for people with and without cardiovascular disease, according to new research published in the American Heart Association’s peer-reviewed journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB).
“We found a long-term cardiovascular health risk associated with COVID, especially among people with more severe COVID cases that required hospitalisation,” said lead study author James Hilser, M.P.H., Ph.D.-candidate at the University of Southern California Keck School of Medicine in Los Angeles. “This increased risk of heart attack and stroke continued three years after COVID infection. Remarkably, in some cases, the increased risk was almost as high as having a known cardiovascular risk factor such as Type 2 diabetes or peripheral artery disease.”
Previous research has shown that COVID increases the risk of serious cardiovascular complications within the first month after infection. This study examined how long the increased risk lasted and whether it subsided after recovering from COVID infection.
Researchers reviewed health and genetic data in the UK Biobank for more than 10 000 adults, including approximately 8000 who had tested positive for SARS-CoV-2 from February 1 to December 31, 2020 and about 2000 who tested positive for the virus in a hospital setting in 2020. A group of more than 200,000 adults who had no history of COVID infection during the same time frame in the UK Biobank were also reviewed for comparison. None of the participants were vaccinated at the time of infection because COVID vaccines were not yet available in 2020.
The analysis found:
During the nearly 3-year follow-up period, the risk of heart attack, stroke and death was more than two times higher among adults who had COVID, and nearly four times greater among adults hospitalized with COVID, compared with the group with no history of COVID infection.
People hospitalized with COVID, without cardiovascular disease or without Type 2 diabetes, had a 21% greater risk of heart attack, stroke and death compared to people with cardiovascular disease and without COVID infection.
There was a significant genetic interaction among the non-O blood types and hospitalisation for COVID. People with severe COVID infections had an increased risk of heart attack and stroke, however, that risk was even higher in people who had non-O blood types (those with blood types A, B or AB).
The risk of heart attack and stroke was about 65% higher in adults with non-O blood types compared to those who had type O blood. A preliminary analysis did not show that Rh (positive or negative) blood type interacted with severe COVID, the authors noted.
“Worldwide, over a billion people have already experienced COVID infection. The findings reported are not a small effect in a small subgroup,” said co-senior study author Stanley Hazen, M.D., Ph.D., chair of cardiovascular and metabolic sciences in Cleveland Clinic’s Lerner Research Institute and co-section head of preventive cardiology. “The results included nearly a quarter million people and point to a finding of global health care importance that may translate into an explanation for a rise in cardiovascular disease around the world.”
Study details, background and design:
Health data was from the UK Biobank, a large-scale study of 503,325 adults living in the United Kingdom who were 40 to 69 years of age at enrollment between 2006 and 2010. The in-depth health and biomedical information was collected for participants registered in the UK National Health Service with a UK general practitioner (similar to a primary care physician in the U.S.).
This analysis included health data for 10,005 adults who tested positive for the COVID virus or were hospitalized with COVID between February 1, 2020, and December 31, 2020. An additional 217,730 peers enrolled in the UK Biobank who did not have COVID during the same time period were included. In the analysis, all participants were matched as closely as possible for demographics and similar health conditions.
Major adverse cardiovascular events (heart attack, stroke and all-cause death) were evaluated for long-term risk, through October 31, 2022, approximately 3 years later.
“This interesting paper is really two studies in one,” said Sandeep R. Das, M.D., M.P.H., MBA, FAHA, co-chair of the American Heart Association’s COVID-19 CVD Registry committee and director for quality and value in the cardiology division for UT Southwestern Medical Center in Dallas. “First, the authors show that having been hospitalized with COVID is a marker of increased cardiovascular risk, on par with having a pre-existing diagnosis of cardiovascular disease. Although proving direct cause and effect is very difficult to tease out in a study that only analyses past data collected for other purposes, this finding is important because it suggests a history of prior COVID hospitalization, even without a history of CVD, should be considered to initiate and possibly accelerate CVD prevention efforts. Whether severe COVID infection has a direct impact on the vascular system is an interesting area for study as well,” Das said.
“The second ‘study’ in this paper looks at the relationship between ABO blood type and COVID outcomes. They show that something located close to the genetic home of ABO blood type is associated with different degrees of susceptibility to COVID. This is really fascinating, and I look forward to seeing scientists tease out what the specific pathway may be.”
The study had several limitations, including that the data was from patients who had the original strain of the COVID virus before vaccines were widely available in 2021. Additionally, the researchers noted that UK Biobank information on medication use was not specific to the beginning of the pandemic in 2020 or the date that patients were infected with SARS-CoV-2. Also, because the majority of participants in the UK Biobank are white, additional research is needed to confirm that these results apply to people with diverse racial and ethnic backgrounds.
“The results of our study highlight the long-term cardiovascular effects of COVID infection. Given the increased risk of heart attack, stroke and death, the question is whether or not severe COVID should be considered as another risk factor for CVD, much like Type 2 diabetes or peripheral artery disease, where treatment focused on CVD prevention may be valuable,” said co-senior study author Hooman Allayee, Ph.D., a professor of population and public health sciences at the University of Southern California Keck School of Medicine in Los Angeles. “The results suggest that people with prior COVID infection may benefit from preventive care for cardiovascular disease.”
Medicine is subjecting the negative effects of alcohol on body and health to ever greater scrutiny – not surprisingly us, as alcohol is one of the strongest cell toxins that exist. In a recent study, doctors at took mobile ECG monitors along to parties of young people who had one principal aim: to drink and be merry. Yet the science produced by the MunichBREW II study made for sobering reading. It revealed that binge drinking can have a concerning effect on the hearts even of healthy young people in surprisingly many cases, including the development of clinically relevant arrhythmias. The results of the study have just been published in the European Heart Journal.
The team from the Department of Cardiologyat LMU University Hospital launched the MunichBREW I study at Munich Oktoberfest in 2015. Back then, the doctors, led by Professor Stefan Brunnerand PD Dr Moritz Sinner, studied the connection between excessive alcohol consumption and cardiac arrhythmias – but only through an electrocardiogram (ECG) snapshot.
Now the scientists wanted to gain a more detailed picture, so they set out with their mobile equipment once again. Their destinations were various small parties attended by young adults with a high likelihood “that many of the partygoers would reach breath alcohol concentrations (BAC) of at least 1.2 grams per kilogram,” says Stefan Brunner. These were the participants of the MunichBREW II study – the world’s largest investigation to date of acute alcohol consumption and ECG changes in prolonged ECGs spanning several days.
Hearts out of sync – especially in recovery phase
Overall, the researchers evaluated the data of over 200 partygoers who, with peak blood alcohol values of up to 2.5 grams per kilogram, had imbibed quite a few drinks. The ECG devices monitored their cardiac rhythms for a total of 48 hours, with the researchers distinguishing between the baseline (hour 0), the drinking period (hours 1-5), the recovery period (hours 6-19), and two control periods corresponding to 24 hours after the drinking and recovery periods, respectively. Acute alcohol intake was monitored by BAC measurements during the drinking period. ECGs were analysed for heart rate, heart rate variability, atrial fibrillation, and other types of cardiac arrhythmia. Despite the festive mood of the study participants, the quality of the ECGs was almost universally high throughout.
“Clinically relevant arrhythmias were detected in over five percent of otherwise healthy participants,” explains Moritz Sinner, “and primarily in the recovery phase.” Alcohol intake during the drinking period led to an increasingly rapid pulse of over 100 beats per minute. Alcohol, it would seem, can profoundly affect the autonomous regulatory processes of the heart. “Our study furnishes, from a cardiological perspective, another negative effect of acute excessive alcohol consumption on health,” stresses Brunner. Meanwhile, the long-term harmful effects of alcohol-related cardiac arrhythmias on cardiac health remains a subject for further research.
A study led by Johns Hopkins Medicine researchers concludes that commonly used ways of positioning the patient’s arm during blood pressure (BP) screenings can substantially overestimate test results and may lead to a misdiagnosis of hypertension.
In a report on the study, published in JAMA Internal Medicine, investigators examined the effects of three different arm positions: an arm supported on a desk, arm supported on a lap, and an unsupported arm hanging at the patient’s side. Researchers found that lap support overestimated systolic pressure by nearly 4mmHg, and an unsupported arm hanging at the side overestimated systolic pressure by nearly 7mmHg.
The findings confirm that arm position makes a “huge difference” when it comes to an accurate blood pressure measurement, says Tammy Brady, MD, PhD, senior author of the study. And they underscore the importance of adhering to clinical guidelines calling for firm support on a desk or other surface when measuring blood pressure, the investigators add.
The latest clinical practice guidelines from the American Heart Association emphasise several key steps for an accurate measurement – including appropriate cuff size, back support, feet flat on the floor with legs uncrossed, and an appropriate arm position, in which the middle of an adjustable BP cuff is positioned at mid-heart level on an arm supported on a desk or table.
Despite these recommendations, the researchers say BP is too often measured with patients seated on an exam table without any, or inadequate, arm support. In some cases, a clinician holds the arm, or the patient holds an arm in their lap. In the new Johns Hopkins study, the researchers recruited 133 adult participants (78% Black, 52% female) between Aug. 9, 2022, and June 1, 2023. Study participants, who ranged from age 18 to 80, were sorted at random into one of six possible groups that differed by order of the three seated arm positions. Measurements were taken during a single visit between 9 a.m. and 6 p.m. Before BP measures were taken, all participants first emptied their bladders and then walked for two minutes to mimic a typical clinical scenario in which people walk into a clinic or office before screening takes place. They then underwent a five-minute, seated rest period with their backs and feet supported. Each person, wearing an upper arm BP cuff selected and sized based on their upper arm size, had three sets of triplicate measurements taken with a digital blood pressure device 30 seconds apart.
Upon completion of each set of three measurements, the cuff was removed, participants walked for two minutes and rested for five minutes. In the same visit, they then underwent a fourth set of triplicate measurements with their arm supported on a desk, a set used to account for well-known variations in BP readings. All of the measurements were conducted in a quiet and private space, and participants were asked not to talk to researchers or use their phones during the screening.
Researchers found that BP measurements obtained with arm positions frequently used in clinical practice – an arm on the lap or unsupported at the side – were markedly higher than those obtained when the arm was supported on a desk, the standard, recommended arm position. Supporting the arm on the lap overestimated systolic and diastolic BP by 3.9mmHg and 4.0mmHg, respectively. An unsupported arm at the side overestimated systolic by 6.5mmHg and diastolic by 4.4mmHg.
“If you are consistently measuring blood pressure with an unsupported arm, and that gives you an overestimated BP of 6.5mmHg, that’s a potential difference between a systolic BP of 123 and 130, or 133 and 140 – which is considered stage 2 hypertension,” says study author Sherry Liu, MHS, an epidemiology research coordinator at Johns Hopkins Bloomberg School of Public Health.
Investigators caution that their study results may only apply during screenings with automated BP devices, and may not apply to readings done with other BP devices.
However, Brady says, the findings suggest that clinicians need to pay better attention to best practice guidelines, and that patients “must advocate for themselves in the clinical setting and when measuring their BP at home.”
Right side heart failure. Credit: Scientific Animations CC4.0
Scientists have discovered a potential new treatment for heart failure with preserved ejection fraction (HFpEF), a type of heart disease that is notoriously difficult to treat. The diseased heart cells were found to have high levels of glucagon activity, a pancreatic hormone that raises blood glucose levels. The scientists then demonstrated that a drug that blocks the hormone’s activity can significantly improve heart function.
In heart failure, which is considered a global pandemic, the heart can no longer pump blood effectively. Globally, an estimated 64 million people live with this condition with HFpEF accounting for around half of the cases.
In HFpEF, the heart can pump normally but its muscles are too stiff to relax to re-fill the chambers with blood properly. It is often seen in older adults and people with multiple risk factors including high blood pressure (hypertension), obesity and diabetes. They typically have symptoms such as shortness of breath, fatigue and reduced ability to exercise. This is unlike heart failure with reduced ejection fraction (HFrEF), where heart muscle is weakened and pumping volume reduced.
There have been studies on how the heart is stressed by hypertension and metabolic diseases associated with obesity, such as diabetes, but these have been done in isolation of each other. This latest study, which was published in Circulation Research, addresses this gap by taking into account both stressors, revealing for the first time, the molecular pathway that contributes to HFpEF progression.
In pre-clinical studies, the team of scientists, which included collaborators from the University of Cincinnati College of Medicine, University of California Los Angeles, University of Toronto and University of North Carolina School of Medicine, investigated how stress from hypertension affected lean hearts versus diabetic/obese ones. In their findings, the lean models developed heart failure with reduced ejection fraction (HFrEF), typically observed in hypertensive patients. The obese models however, developed heart failure with preserved ejection fraction (HFpEF), proving that a combination of stressors give rise to the disease and providing a good model for further studies.
Using advanced single-cell RNA-sequencing technologies, the scientists were then able to study the expression of every detected gene in every single heart cell, allowing them to uncover specific genetic variations in cells associated with HFpEF. The scientists found that in the obese models, the most active genes were the ones driving the activity of glucagon.
Professor Wang Yibin, Director of the Cardiovascular & Metabolic Disorders Programme at Duke-NUS and senior author of the study, said:
“Under stress conditions such as high blood pressure and metabolic disorders like obesity and diabetes, we found that glucagon signalling becomes excessively active in heart cells. This heightened activity contributes to the development of heart failure with preserved ejection fraction (HFpEF) by increasing heart stiffness and impairing its ability to relax and fill with blood.”
The team then tested a drug that blocks the glucagon receptor in a pre-clinical model of HFpEF and found significant improvements in heart function, including reduced heart stiffness, enhanced relaxation, improved blood filling capacity and overall better heart performance.
Assistant Professor Chen Gao from the Department of Pharmacology, Physiology and Neurobiology at the University of Cincinnati College of Medicine; and the study’s first author, said:
“Our study shows strong evidence that a glucagon receptor blocker could work well to treat HFpEF. Repurposing this drug, which is already being tested in clinical trials for diabetes, could bypass the lengthy drug development process and provide quicker and more effective relief to millions of heart patients.”
“With our ageing population, there will likely be more patients with multiple conditions, including heart failure, diabetes and hypertension, presenting a significant challenge to health systems. Uncovering the synergistic impact of such illnesses and their underlying mechanisms is key to better understanding the complex process of heart failure and developing an effective treatment for the disease.”
The researchers hope to work with clinical partners to conduct clinical trials to test the glucagon receptor blocker in humans with HFpEF. If these succeed, it could become one of the first effective treatments for this challenging condition, significantly improving the quality of life for millions worldwide.
The risk of being born with a major heart defect is 36% higher in babies who were conceived after assisted reproductive technology, such as in vitro fertilisation (IVF), according to results of a very large study published in the European Heart Journal.
Researchers say the finding is important since congenital heart defects are the most common form of birth defects, and some of them are associated with life threatening complications.
The study also shows that the increase in risk is particularly associated with multiple births which are more common in assisted reproduction.
The study was led by Professor Ulla-Britt Wennerholm from the University of Gothenburg in Sweden. She said: “Previous research shows that there are increased risks for babies conceived with the help of assisted reproductive technology. These include preterm birth and low birth weight. We wanted to investigate whether the risk of heart defects was higher for babies born following assisted reproduction.”
The research included all liveborn children born in Denmark between 1994 and 2014, all children born in Finland between 1990 and 2014, those born in Norway between 1984 and 2015 and those born in Sweden from 1987 to 2015; more than 7.7 million in total.
Researchers compared data on babies born following assisted reproduction, including IVF, intracytoplasmic sperm injection (ICSI) and embryo freezing, with data on babies conceived naturally.
They assessed how many liveborn children in each group were diagnosed with a major heart defect or with a serious heart defect either in the womb or in the first year of life. They took into account other factors that can increase the risk of congenital heart defects, such as child’s year of birth, country of birth, mother’s age at delivery, if the mother smoked during pregnancy, or if the mother had diabetes or heart defects.
This showed that heart defects were around 36% more common in babies born after assisted reproduction, compared to babies conceived without such treatment (absolute risk 1.84% vs 1.15%). This risk was similar regardless of the type of assisted reproduction used (IVF or ICSI, fresh or frozen embryos). However, the risk was greater for multiple births following assisted reproduction compared to singleton births following assisted reproduction (2.47% vs 1.62%).
Professor Wennerholm said: “We already know that babies born after assisted reproductive technology have a higher risk of birth defects in general however, we have found a higher risk also in congenital heart defects, the most common major birth defect.
“The fact that the risk of heart defects is similar regardless of the type of assisted reproduction used may indicate that there is some common factor underlying infertility in parents and congenital heart disease in their babies.
“Congenital heart defects can be extremely serious requiring specialist surgery when babies are very young, so knowing which babies are at the greatest risk can help us diagnose heart defects as early as possible and ensure the right care and treatment are given. More and more people are conceiving with the help of assisted reproductive technology, so we might expect to see increases in cases of congenital heart defects worldwide.”
In an accompanying editorial, Dr Nathalie Auger from University of Montreal Hospital Research Centre in Canada and colleagues said: “Assisted reproductive technology is a popular intervention in reproductive medicine, with these procedures accounting for 2% to 8% of births depending on the country. While most neonates born after assisted reproductive technology are healthy, these procedures are not without risks.
“In one of the largest studies to date, the researchers found that assisted reproductive technology was associated with the risk of major heart defects diagnosed prenatally or up to one year of age.
“Patients who use assisted reproductive technology tend to differ from the general population. These patients may have underlying morbidities that affect both fertility and the risk of heart defects.”
Atrial fibrillation, a rapid, irregular heartbeat that can lead to stroke or sudden death, is three times more common than previously thought, affecting nearly 5% of the population, according to new estimates from UC San Francisco.
A-Fib, as the condition is commonly known, has been on the rise for at least the past decade, driven by the aging of the population, along with increasing rates of hypertension, diabetes and obesity. Earlier projections had estimated that 3.3 million U.S. adults had atrial fibrillation, but these have not been updated in more than two decades.
“Atrial fibrillation doubles the risk of mortality, is one of the most common causes of stroke, increases risks of heart failure, myocardial infarction, chronic kidney disease and dementia, and results in lower quality of life,” said first author Jean Jacques Noubiap, MD, PhD, a postdoctoral scholar at UCSF with a specialty in global cardiovascular health.
“Fortunately, atrial fibrillation is preventable, and early detection and appropriate treatment can substantially reduce its adverse outcomes,” he said.
Rising numbers reflect need for better prevention and treatment
UCSF investigators reviewed the medical records of nearly 30 million adult patients who received some form of acute or procedural care in California from 2005 to 2019. About 2 million of these people had been diagnosed with A-Fib, and the numbers grew over time, rising from 4.49% of the patients treated between 2005 and 2009 to 6.82% of the patients treated between 2015 and 2019.
The data were standardised to reflect the entire country, and researchers estimated the current national prevalence to be at least 10.55 million. They also found that during the study timeframe, A-Fib patients skewed younger, were less likely to be female and more likely to have hypertension and diabetes.
A-Fib has a broad spectrum of complications from shortness of breath and light-headedness to blood clots, stroke and even heart failure. Studies have shown that people with A-Fib are up to five times more likely to have a stroke. The authors said that by outlining the scope of the problem, these new estimates can help guide health care planning, resource allocation and public health interventions.
“Physicians recognise that atrial fibrillation is often encountered in essentially every field of practice,” said senior and corresponding author Gregory M. Marcus, MD, MAS, a cardiologist and electrophysiologist at UCSF Health. “These data provide objective evidence to demonstrate that prior projections severely underestimated how common it truly is.”
Digital technologies may reveal it is even more common than the current analysis indicates.
“With the growing use of consumer wearables designed to detect atrial fibrillation combined with safer and more effective means to treat it, this current prevalence of atrial fibrillation in health care settings may soon be dwarfed by future health care utilisation that will occur due to the disease,” Marcus said.
