Radiation therapy may be potential heart failure treatment

 Cardiologists and radiation oncologists at Washington University School of Medicine in St. Louis pioneered the use of radiation therapy -- a strategy typically used against cancer -- to treat patients with a life-threatening abnormal heart rhythm called ventricular tachycardia.

Now, after studying the cardiac effects of radiation in a small number of these patients and modeling the effects of low-dose radiation in mice with heart failure, the research team has found that low-dose radiation therapy appears to improve heart function in various forms of heart failure.

More research is needed before the investigators can evaluate this therapy in patients with heart failure, but the study suggests that radiation's effects on injured hearts with high levels of inflammation may be more varied -- and perhaps beneficial -- than previously understood.

The study, published Nov. 28 in the journal Med, suggests that low-dose radiation therapy improves heart function, at least in part, by reducing the number of inflammatory immune cells in the heart muscle.

"The radiation therapy used to treat ventricular tachycardia is targeted to a specific location in the heart; however, a large portion of the rest of the heart gets a low-dose exposure," said co-senior author and cardiologist Ali Javaheri, MD, PhD, an assistant professor of medicine.

"We wanted to understand the effects of that low-dose radiation on these patients' hearts. There was concern that it could be harmful to overall heart function, even though it treats dangerous arrhythmia. We were surprised to find the opposite: Heart function appeared to be improved after radiation therapy, at least in the short term."

About 6.2 million American adults currently live with heart failure, according to the Centers for Disease Control and Prevention.

More than half of heart failure patients hospitalized for the condition die within five years of that first hospitalization, demonstrating a need for better therapies.

A failing heart gradually loses its ability to properly supply the body with oxygenated blood.

A complex condition, heart failure can have diverse triggers, including a past heart attack, viral infection or chronic arrhythmias such as ventricular tachycardia.

A group of nine patients with ventricular tachycardia was evaluated with cardiac MRI before and after radiation treatment, with the MRIs showing improved heart function soon after radiation.

In particular, the patients' hearts showed improved pumping capacity of the left ventricle, which supplies blood to the entire body.

The improvement was seen a few days after treatment, so it was deemed unlikely to be due to the reduction of the arrhythmia, which happens more gradually over the ensuing weeks and months.

The researchers also studied the effects of similar low-dose radiation to the heart in groups of mice with heart failure from three different causes.

Source: ScienceDaily

First multi-chamber heart organoids unravel human heart development and disease

 Heart disease kills 18 million people each year, but the development of new therapies faces a bottleneck: no physiological model of the entire human heart exists -- so far. A new multi-chamber organoid that mirrors the heart's intricate structure enables scientists to advance screening platforms for drug development, toxicology studies, and understanding heart development. The new findings, using heart organoid models developed by Sasha Mendjan's group at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences, are presented in the journal Cell on November 28.

Cardiovascular disease is the leading cause of death worldwide, but only a few new therapies are on the horizon. Similarly, one in every 50 babies born suffers from a congenital heart defect -- and again, therapies are few and far between, as we know little why they arise. What is missing in understanding both heart disease and cardiac malformations is a model comprising the major regions of the human heart. Now, the Mendjan team at IMBA presents the first physiological organoid model that includes all the principal developing heart structures and allows researchers to study cardiac disease and development.

In 2021, the Mendjan lab presented the first chamber-like organoid heart model formed from human induced pluripotent stem cells. These self-organizing heart organoids, or Cardioids, recapitulated the development of the heart's left ventricular chamber in the very early days of embryogenesis. "These Cardioids were a proof-of-principle and an important step forward," says Mendjan. "While most adult diseases affect the left ventricle, which pumps oxygenated blood through the body, congenital defects affect mostly other heart regions essential to establish and maintain circulation."

In the new study, the team at IMBA expanded on their previous work. The researchers first derived organoid models of each developing heart structure individually. "Then we asked: If we let all these organoids co-develop together, do we get a heart model that co-ordinately beats like the early human heart?," Mendjan explains.

Unraveling human heart development

After growing left and right ventricular and the atrial organoids together, the researchers were in for a surprise: "Indeed, an electrical signal spread from the atrium to the left and then the right ventricular chambers -- just like in early fetal heart development in animals," Mendjan recalls. "We now observed this fundamental process in a human heart model for the first time, with all its chambers."

While the previous Cardioid model allowed the researchers to study the chamber's shape and tissue organization, the newly developed multi-chamber Cardioids enabled them to go beyond, studying how regional gene expression differences lead to specific chamber contraction patterns and intricate communication between them.

The researchers have already gained insight into early heart development, particularly how the human heart starts beating -- which has not been understood so far. "We saw that as the organoid chambers developed, they performed an intricate dance of lead and follow. At first, the left ventricular chamber leads the budding right ventricular and atrium chambers at its rhythm. Then, as the atrium develops- two days later- the ventricles follow the atrial lead. This mirrors what is seen in animals before the final leaders, the pacemakers, control the heart rhythm," explains Alison Deyett, a PhD student in the Mendjan group and one of the study's first authors.

Source: ScienceDaily

Coronary heart disease before age 45 may increase risk of dementia later in life

 Adults diagnosed with coronary heart disease, especially before the age of 45, may be at increased risk of developing dementia, Alzheimer's disease and vascular dementia later in life, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

"Coronary heart disease has previously been associated with dementia risk in older adults, however, this is believed to be the first large-scale study examining whether the age of coronary heart disease onset may impact the risk of developing dementia later in life," said Fanfan Zheng, Ph.D., senior study author and researcher in the School of Nursing at the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing, China.

"In previous research, we found that adults experienced accelerated cognitive decline after new diagnoses of coronary heart disease," she said.

The researchers assessed the potential relationship between age at coronary heart disease onset and the development of dementia by analyzing health data from the UK Biobank.

The analysis found:

• Among the 432,667 participants in the study, there were 5,876 cases of dementia, 2,540 cases of Alzheimer's disease and 1,220 cases of vascular dementia that occurred over an average of 13 years of follow-up.
• Compared with participants who did not have coronary heart disease, participants with coronary heart disease had higher risks of developing dementia from any cause, Alzheimer's disease and vascular dementia.
• After adjusting the analysis for demographic and lifestyle factors, participants with coronary heart disease had a 36% increased risk of developing dementia, a 13% increased risk of developing Alzheimer's and a 78% greater risk of developing vascular dementia.
• Earlier coronary heart disease-onset was associated with a 25% increased risk of dementia, a 29% increased risk of Alzheimer's disease and a 22% increased risk of vascular dementia.
• The risk of dementia rose in direct proportion to the younger age of coronary heart disease onset (per 10-year decrease in age).
• Participants diagnosed with coronary heart disease before age 45 had a significantly increased risk of developing dementia compared to their counterparts who did not have coronary heart disease.

"What surprised us most was the linear relationship between age of coronary heart disease onset and dementia. This shows the huge detrimental influence of premature coronary heart disease on brain health," Zheng said. "As more people live longer and are diagnosed with coronary heart disease at a younger age, it's likely there will be a large increase in the number of people living with dementia in years to come. Health care professionals should be aware of individuals diagnosed with coronary heart disease at a young age. The next step is to determine whether modifying cardiovascular risk early in life will promote better brain health later in life."

Alcohol consumption may have positive and negative effects on cardiovascular disease risk

 While past research has indicated that moderate alcohol consumption can lower one's risk of cardiovascular disease (CVD), more recent studiessuggest that moderate levels of drinking may be hazardous to heart health. A new analysis led by Boston University School of Public Health and Friedman School of Nutrition Science and Policy at Tufts University (Friedman School) now sheds new insight on this complex relationship between alcohol consumption and the progression of CVD.

Published in the journal BMC Medicine, the study found that alcohol consumption may have counteractive effects on CVD risk, depending on the biological presence of certain circulating metabolites -- molecules that are produced during or after a substance is metabolized and studied as biomarkers of many diseases.

The researchers observed a total of 60 alcohol consumption-related metabolites, identifying seven circulating metabolites that link long-term moderate alcohol consumption with an increased risk of CVD, and three circulating metabolites that link this same drinking pattern with a lower risk of CVD.

The findings provide a better understanding of the molecular pathway of long-term alcohol consumption and highlight the need for and direction of further research on these metabolites to inform targeted prevention and treatment of alcohol-related CVD.

"The study findings demonstrate that alcohol consumption may trigger changes of our metabolomic profiles, potentially yielding both beneficial and harmful outcomes," says Dr.Chunyu Liu, assistant professor of biostatistics at BUSPH and co-corresponding/co-senior author of the study along with Dr.Jiantao Ma, assistant professor in the Division of Nutrition Epidemiology and Data Science at the Friedman School.

"However, rather than definitively settling that debate, this study underscores the intricate effects of alcohol consumption on cardiovascular health and generates a useful hypothesis for future investigations," Dr. Liu says.

For the study, the researchers examined blood samples to measure the association between the cumulative average consumption of beer, wine, and liquor and 211 metabolites among 2,428Framingham Heart Study Offspring Study participants, who are the children of participants in the long-running Boston University-basedFramingham Heart Study, over 20 years.

Among the participants, 636 developed CVD over the study period.

Among the 60 drinking-related metabolites, 13 metabolites had a stronger association with alcohol consumption in women than in men, perhaps due to women's generally smaller body size and likely higher blood alcohol concentration after consuming the same amount of alcohol as men.

The results also showed that consumption of different types of alcohol was linked to different metabolomic responses, with beer consumption generating a slightly weaker association overall than wine and liquor.

In roughly two-thirds of the 60 metabolites, higher plasma levels were detected in participants who consumed greater amounts of alcohol.

Source: ScienceDaily

Novel study finds aspirin-free regimen benefits patients with LVAD

 The ARIES-HM3 Randomized Clinical Trial assessed the safety and efficacy of excluding aspirin from the antithrombotic regimen in patients with advanced heart failure who have undergone implantation of a fully magnetically levitated left ventricular assist device (LVAD).

"We can now safely say that not giving aspirin is not only safe from a thromboembolic risk profile but results in improved adverse event rate by a significant reduction in non-surgical bleeding which is a well-known complication related to LVAD therapy," said Mirnela Byku, M.D., Ph.D., MBA, co-author of the study and director of the UNC Durable Mechanical Circulatory Device Program at the UNC School of Medicine.

"Improving not only longevity but also reducing morbidity and improving quality of life is a big focus in the field of MCS."

Until this study, there had been no consensus in the field about use of or dose of aspirin in the LVAD population.

The paper was published in JAMA.

The international clinical trial followed a randomized, double-blind, placebo-controlled design and involved 628 patients across 51 centers in 9 countries.

The patients were divided into two groups: one receiving aspirin (100mg/d) and the other receiving a placebo in addition to vitamin K antagonist (VKA) therapy.

A focus was to determine if the likelihood a patient experiences major nonsurgical hemocompatibility-related adverse events (such as stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) within 12 months differed between the two groups.

The results showed not giving aspirin to patients with advanced heart failure, treated with a fully magnetically levitated LVAD who are receiving VKAs, did not make their survival worse. Furthermore, aspirin avoidance was associated with a significant reduction (34%) in major nonsurgical bleeding events.

Source: ScienceDaily

Pulling an all-nighter? Don't follow with an important decision

 Research gives insight into importance of sleep on cognitive performance and emotional well-being to those who find themselves under stress

Politicians, military generals and first responders are just some high-stress positions which should avoid taking important decisions after a night without sleep, new research from the University of Ottawa indicates.

We all understand the power of sleep and the vital role it plays in human health, cognitive performance and in regulating our emotional well-beingNumerous studies into a lack of sleep have shown drops in neurocognitive functions, particularly vigilant attention, motor responses, inhibition control, and working memory.

Despite this, sleep loss continues to challenge public health and affect people of all ages.

Sleep and risky decision-making

With little insight into the impact of a lack of sleep on risky decision-making at the neuroimaging level, researchers from the University of Ottawa and the University of Pennsylvania found a 24-hour period of sleep deprivation significantly impacted individuals' decision-making processes by dampening neural responses to the outcomes of their choices.

In other words, people tend to exhibit reduced positive emotions in response to winning outcomes and diminished negative emotions when faced with losses after pulling an all-nighter compared to their well-rested baseline condition.

"Common sense does dictate if people incur sleep loss, sleep disturbance or a sleep disorder that their cognitive function will be impacted, their attention and efficiency will decrease. But there is an emotional impact, too," says Zhuo Fang, a Data Scientist in the Department of Psychology at the Faculty of Social Sciences.

"If you experience even just one night of sleep deprivation, there will be an impact, even on a neural level. So, we wanted to combine brain imaging and behaviour to see that impact," adds Fang, who is affiliated with uOttawa's Brain and Mind Research Institute and The Royal.

The study, which evaluated the impact of one night of total sleep deprivation on 56 healthy adults, found:

• A single night of total sleep loss significantly decreased the brain activation to win and loss outcomes, suggesting that acute sleep loss can have a dampening effect on neural responses to decision outcomes during risk-taking.
• Total sleep deprivation had the detrimental effect by disrupting the relationship between neural response and individual's risk-taking behavior, which might be related to the altered perception for risk-taking.

While numerous studies have previously illustrated the wide-ranging effects of sleep deprivation on various brain and cognitive functions, including attention processing, memory consolidation, and learning, this study addresses the specific impact of sleep loss on decision-making.

sources-science daily

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Researchers identify cell signaling pathway controlling melanoma cell metastasis to the brain

 Melanoma is the deadliest form of skin cancer because of its ability to quickly grow and spread throughout the body. More than half of those with advanced melanoma will see the disease spread to the brain, where it rapidly progresses, often leading to death in only three to four months. Researchers in Moffitt Cancer Center's Donald A. Adam Melanoma and Skin Cancer Center of Excellence have been working to better understand what drives melanoma brain metastasis. In a new study published in Nature Communications, they report on the identification of a cell signaling pathway that regulates the metastatic spread of melanoma cells to the brain.

Melanoma tumors are composed of subgroups of cells with different gene expression patterns with varied abilities to invade surrounding tissues and survive anticancer treatments.

It is unclear how these different melanoma subgroups contribute to tumor development and progression.

n previous studies, Moffitt researchers determined that the protein HDAC8 regulated resistance to BRAF and MEK inhibitors commonly used to treat melanoma.

HDAC8 removes chemical modifications called acetyl groups from other proteins, leading to alterations in gene expression patterns.

The Moffitt team hypothesized that HDAC8 may also be involved in the regulation of gene expression patterns of melanoma cell subgroups.

The researchers performed laboratory experiments and demonstrated that HDAC8 activity increased melanoma cell survival under stress conditions, including low oxygen, UV radiation, and BRAF/MEK inhibitor treatment.

HDAC8 activity also changed the gene expression pattern of melanoma cells and caused the cells to develop characteristics associated with cell subgroups that were able to migrate into and invade surrounding sites.

Their pre-clinical experiments found that increased HDAC8 expression and activity enhanced the ability of melanoma cells to metastasize to the brain, while no significant impact was observed in the number of metastatic tumors to other organs, such as the liver or lung.

The researchers further investigated the molecular pathways of HDAC8-mediated brain metastasis and discovered that HDAC8 chemically modified the protein EP300, which subsequently caused cells to develop invasive characteristics.

sources-science daily