Heart cells cozy up to prevent deadly arrhythmias


Blood may seem like a simple fluid, but its chemistry is complex. When too much potassium, for instance, accumulates in the bloodstream, patients may experience deadly irregular heart rhythms.

Cardiovascular scientists at Virginia Tech’s Fralin Biomedical Research Institute at VTC are studying why.

In a new study, published in Pflügers Archiv European Journal of Physiology, the research team led by Steven Poelzing, associate professor at the institute, describes how subtle changes in potassium, calcium, and sodium levels regulate heartbeats.

Poelzing says that the results could help researchers and physicians understand the nuances of cardiac arrythmias, as well as a group of genetic disorders that impact sodium channel function, such as Brugada syndrome.

The scientists elevated blood potassium in guinea pigs, creating a condition called hyperkalemia, which causes some of the heart’s key electrical conduits, sodium channels, to shut down. Next, they increased calcium levels and observed the heart muscle cells pressing closer together. This miniscule motion—spanning mere nanometers—helps preserve electrical conduction in the heart.

“We know the heart is extremely sensitive to changes in blood electrolyte levels, but until recently we didn’t have a great picture of how the heart’s molecular landscape is remodeled, and how these muscle cells adapt,” said Poelzing, who is also an associate professor in the Virginia Tech College of Engineering’s department of biomedical engineering and mechanics.

Heart muscle cells primarily pass electrical signals via a network of protein bridges called gap junctions and sodium channels. These pathways let nutrients and positively charged minerals flow between cells. When there are too many positively charged potassium ions in the blood, however, the cells get overstimulated and temporarily block signaling channels.

“This can be dangerous when sodium channels get stuck in a half-closed state. The cell isn’t dying, but it’s not as electrically active as it once was. This can cause dangerous heart arrythmias and sudden cardiac death,” Poelzing said.

When the heart’s core electrical pathways falter, heart muscle cells press closer together, allowing them to sense subtle electric fields generated by neighboring cells. This secondary form of cell-to-cell signaling is known as ephaptic coupling.

“Ephaptic coupling appears to address the effects of a functional loss of sodium channels, in this case caused by high potassium, and helps keep the current flowing properly across the heart muscle,” Poelzing said.

Over the course of the eight-year study, Poelzing’s team tested different concentrations of sodium and calcium to treat the electrical defects associated with high potassium to see how the heart would respond. They discovered that increasing sodium and calcium levels together greatly reduced the distances between cells, providing a substantial improvement in cardiac conduction.

In the clinic, human patients with hyperkalemia who develop abnormal heart rhythms are administered intravenous calcium gluconate. Poelzing’s findings help explain why elevating calcium levels under these certain clinical conditions is beneficial.

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Study helps unravel why pregnant women develop heart failure similar to older patients

pregnant women

Researchers at Penn Medicine have identified more genetic mutations that strongly predispose younger, otherwise healthy women to peripartum cardiomyopathy (PPCM), a rare condition characterized by weakness of the heart muscle that begins sometime during the final month of pregnancy through five months after delivery. PPCM can cause severe heart failure and often leads to lifelong heart failure and even death. The study is published today in Circulation.

PPCM affects women in one out of every 2,000 deliveries worldwide, with about a third of those women developing heart failure for life, and about five percent of them dying within a few years. Maternal mortality in the United States has doubled in the last 20 years, and PPCM is a leading cause of these deaths. Previously, the reasons behind why women developed PPCM remained a mystery until a 2016 study strongly suggested that some genetic mutations predispose women to the disease. Zoltan P. Arany, MD, PHD, the Samuel Bellet Professor of Cardiology in the Perelman School of Medicine at the University of Pennsylvania was also the senior author of that study. This newly released study shines a light on four more genetic variants that had not previously been associated with PPCM. It found that this genetic profile is highly similar to that found in patients with non-ischemic dilated cardiomyopathy (DCM), a very similar disease that typically impacts middle-aged men and women, and one that the medical community knows more about.

“This study provides the first extensive genetic and phenotype landscape of PPCM and has major implications for understanding how PPCM and DCM are related to each other,” said Arany. “It shows that predisposition to heart failure is an important risk factor for PPCM, suggesting that approaches being developed for DCM may also apply to patients with PPCM.”

For the study, Penn researchers identified nearly 470 women with PPCM, retrospectively, from several academic centers in the United States and abroad, and looked at clinical information and DNA samples. Then, they performed next-generation sequencing on 67 genes, including a gene known as TTN, which generates a large protein that controls how heart muscle cells contract and pump blood. 10.4 percent of the patients sampled showed shortened variants in the TTN gene, compared with just 1.2 percent of the reference population. Researchers also found overrepresentation of shortened variants in three other genes not previously associated with PPCM, but previously associated with DCM.

Researchers hope this will push for changes to allow physicians to follow similar, well-established genetic testing practices and counseling guidelines already used for patients with DCM, as well as gene-specific therapies.

“We believe this study shows how important genetic screening and counseling are for women who develop PPCM, something that isn’t currently common practice, and perhaps even for their female family members of child-bearing age,” Arany said. “As a physician, knowing you have a patient with PPCM who shows these genetic mutations would lead you to make changes in care, such as lowering the threshold for defibrillator use in the case of high-risk variants, or counseling family members on their risk of developing PPCM.”

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Mediterranean diet with lean beef may lower risk factors for heart disease

lean beef

Eating red meat may have a bad reputation for being bad for the heart, but new research found that lean beef may have a place in healthy diets, after all.

In a randomized controlled study, researchers found that a Mediterranean diet combined with small portions of lean beef helped lower risk factors for developing heart disease, such as LDL cholesterol.

Jennifer Fleming, assistant teaching professor of nutrition at Penn State, said the study suggests that healthy diets can include a wide variety of foods, such as red meat, and still be heart friendly.

“When you create a healthy diet built on fruits, vegetables, and other plant-based foods, it leaves room for moderate amounts of other foods like lean beef,” Fleming said. “There are still important nutrients in beef that you can benefit from by eating lean cuts like the loin or round, or 93% lean ground beef.”

David J. Baer, research leader at the United States Department of Agriculture—Agricultural Research Service, and study co-principal investigator, added, “This study highlights the importance of including lean beef in a Mediterranean dietary pattern that can yield heart-healthy benefits.”

According to the researchers, red meat such as beef has been associated with an increased risk for cardiovascular disease in previous studies. But it has remained unclear whether red meat actually causes these effects or if they actually are caused by other diet and lifestyle choices that people engage in alongside red meat consumption.

Additionally, the researchers said many studies have combined both fresh and processed meats together when evaluating red meat consumption and health. Processed red meats have a very different nutrient profile than fresh meat—for example, processed meat products are much higher in sodium—that could explain the red meat research that has been reported.

“The Mediterranean diet is traditionally low in red meat,” Fleming said. “But, knowing that many Americans enjoy red meat, we wanted to examine how combining lean beef with the Mediterranean diet would affect cardiovascular risk markers.”

The study included 59 participants. Every participant consumed each diet for four weeks each, with a one week break between each diet period, and blood samples were drawn at the beginning of the study as well as after each diet period.

Three of the four diet periods contained different amounts of beef to a Mediterranean diet plan, which provided 41% calories from fat, 42% from carbohydrates and 17% from protein. In addition to the control average American diet, one diet provided 0.5 ounces of beef a day, which is the amount recommended in the Mediterranean diet pyramid. A second diet provided 2.5 ounces a day, which represents the amount an average American eats in a day, and the third experimental diet included 5.5 ounces a day, which previous research connected with certain heart health benefits.

All three Mediterranean diet periods included olive oil as the predominant fat source, three to six servings of fruits, and six or more servings of vegetables a day. The beef included in these diet periods was either lean or extra-lean.

Fleming said they were able to use a special technology called nuclear magnetic resonance—or NMR technology—to measure the number and size of lipoprotein particles. She said this study was one of the first randomized controlled trials of the Mediterranean diet to use the technique.

“This is important because there is growing evidence to suggest that LDL particle number is more strongly associated with cardiovascular disease risk than total blood LDL concentrations alone,” Fleming said. “Moreover, we were able to identify changes in apolipoproteins, specifically apoB, which are also associated with increased CVD risk.”

After the data were analyzed, the researchers found that participants all had lower LDL cholesterol following the Mediterranean diet periods compared to the average American diet. But while the total numbers of LDL particles were reduced following all three Mediterranean diet periods, they were only significantly decreased when following those periods that included 0.5 or 2.5 ounces of beef a day compared to the average American diet.

Additionally, non-HDL cholesterol and apoB—a protein involved in lipid metabolism and a marker of CVD risk—were lower following all three Mediterranean diet periods compared to the average American diet.

Fleming said the study—recently published in the American Journal of Clinical Nutrition—underscores the importance of consuming healthy, well-balanced diets.

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Mouse model closely replicates human NAFLD

Human non-alcoholic fatty liver disease (NAFLD) is a little-understood condition that significantly increases the risk of inflammation, fibrosis and liver cancer and ultimately requires liver transplant.

"NAFLD has been difficult to study mainly because we had no good animal model," said corresponding author Dr. Karl-Dimiter Bissig, who was at Baylor during the development of this project and is now at Duke University.

The disease has both genetic and nutritional components, which have been hard to understand in human studies, and murine models until now had not accurately reflected typical characteristics of human livers with the disease.

Part mouse, part human

Our goal was to have a mouse model that would allow us to study the disorder and test potential treatments. Applying our lab's yearslong expertise developing chimeric mouse models, those that combine both human and murine cells, we developed mice with livers that were part human and part murine."

Dr. Beatrice Bissig-Choisat, co-first author, assistant professor at Duke University

The team fed a high-fat diet to the chimeric mice for 12 weeks, then they looked at the livers under the microscope and also studied their metabolic functions and gene expression, comparing them with those of normal mice and of humans with NAFLD.

"We were surprised by the striking differences we observed under the microscope," Bissig said. "In the same liver, the human liver cells were filled with fat, a typical characteristic of the human disease, while the mouse liver cells remained normal."

Next, the researchers analyzed the products of metabolism, in particular the metabolism of fats, of the human liver cells in the mouse model and identified signatures of clinical NAFLD.

"For instance, when mice that received human liver cells fed on a high-fat diet, they started to show features of cholesterol metabolism that looked more like what a patient shows than what other previous animal models showed," said co-first author Dr. Michele Alves-Bezerra, instructor of molecular physiology and biophysics at Baylor. "We made the same observation regarding genes that are regulated after the high-fat diet. All the analyses pointed at cholesterol metabolism being changed in this model in a way that closely replicates what we see in humans."

The researchers also investigated whether the gene expression profiles of the human liver cells in the chimeric model supported the microscopy and metabolic findings.

"We discovered that, compared to the normal mouse liver cells in our model, the fat-laden human liver cells had higher levels of gene transcripts for enzymes involved in cholesterol synthesis," said co-author Dr. Neil McKenna, associate professor of molecular and cellular biology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. "We wanted to see whether this was also the case in human NAFLD livers."

The team used the web-based platform called the Signaling Pathways Project to create a NAFLD consensome, which surveys previously published clinical studies to identify transcripts whose expression is consistently different between NAFLD livers and healthy ones.

"Using the NAFLD consensome we discovered that, indeed, compared to normal livers, NAFLD livers have consistently higher levels of cholesterol synthesis enzyme transcripts," McKenna said. "This is additional confirmation of the clinical accuracy of our NAFLD model."

Together, the microscopy, metabolic and gene transcription evidence support that the chimeric model closely replicates clinical NAFLD. With this model, researchers have an opportunity to advance the understanding and treatment of this serious condition for which there is no effective therapy.

Not quite human

Another important contribution of this work is that it clearly shows that human and murine cells can be quite different in their responses to factors such as diet, and we have to be careful when interpreting mouse studies of human conditions," Bissig said.

"Here we have a model in which human liver cells respond like in humans. We propose that this model can be used to better understand NAFLD and to identify effective therapies."

The study appeared in JHEP Reports.


Baylor College of Medicine

Journal reference:

Bissig-Choisat, B., et al. (2021) A human liver chimeric mouse model for non-alcoholic fatty liver disease. JHEP Reports. doi.org/10.1016/j.jhepr.2021.100281.

Posted in: Molecular & Structural Biology | Cell Biology

Tags: Animal Model, Blood, Cancer, Cellular Biology, Children, Cholesterol, Diabetes, Diet, Enzyme, Fatty Liver, Fibrosis, Gene, Gene Expression, Genes, Genetic, Heart, Hospital, Inflammation, Kidney, Kidney Disease, Liver, Liver Cancer, Liver Disease, Liver Transplant, Medicine, Metabolism, Microscope, Microscopy, Mouse Model, Physiology, Transcription, Transplant

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Recovered COVID-19 patients may develop blood clots due to overactive immune response

People who have recovered from COVID-19, especially those with pre-existing cardiovascular conditions, may be at risk of developing blood clots due to a lingering and overactive immune response, according to a study led by Nanyang Technological University, Singapore (NTU) scientists.

The team of researchers, led by NTU Assistant Professor Christine Cheung, investigated the possible link between COVID-19 and an increased risk of blood clot formation, shedding new light on "long-haul COVID" – the name given to the medium- and long-term health consequences of COVID-19.

The findings may help to explain why some people who have recovered from COVID-19 exhibit symptoms of blood clotting complications after their initial recovery. In some cases, they are at increased risk of heart attack, stroke or organ failure when blood clots block major arteries to vital organs.

The team, comprising researchers from NTU, Agency for Science, Technology and Research's (A*STAR) Singapore Immunology Network (SIgN), and the National Centre of Infectious Diseases, Singapore (NCID), collected and analysed blood samples from 30 COVID-19 patients a month after they had recovered from the infection and were discharged from hospital.

They found that all recovered COVID-19 patients had signs of blood vessel damage, possibly from a lingering immune response, which may trigger the formation of blood clots.

Their findings were published on 23 March in the peer-reviewed scientific journal eLife.

"With more people recovering from COVID-19, we started hearing from clinicians about patients returning with blood clotting issues after they had been discharged and cleared of the virus," said Asst Prof Christine Cheung from NTU's Lee Kong Chian School of Medicine. "This makes a strong case for the close monitoring of recovered COVID-19 patients, especially those with pre-existing cardiovascular conditions like hypertension and diabetes who have weakened blood vessels."

Blood vessel damage due to post-recovery overactive immune system

The team found that recovered COVID-19 patients had twice the normal number of circulating endothelial cells (CECs) that had been shed from damaged blood vessel walls. The elevated levels of CECs indicate that blood vessel injury is still apparent after recovering from viral infection.

The researchers also found that recovered COVID-19 patients continued to produce high levels of cytokines – proteins produced by immune cells that activate the immune response against pathogens – even in the absence of the virus.

Unusually high numbers of immune cells, known as T cells, that attack and destroy viruses were also present in the blood of recovered COVID-19 patients.

The presence of both cytokines and higher levels of immune cells suggest that the immune systems of recovered COVID-19 patients remained activated even once the virus was gone.

The researchers hypothesise that these persistently activated immune responses may attack the blood vessels of recovered COVID-19 patients, causing even more damage and increasing the risk of blood clot formation further.

While COVID-19 is mainly a respiratory infection, the virus may also attack the linings of blood vessels, causing inflammation and damage. Leakage from these damaged vessels triggers the formation of blood clots that may result in the sort of complications seen in the patients during hospitalisation."

Florence Chioh, Study First Author and Research Assistant, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

One of the co-authors of the paper, Professor Lisa Ng, Executive Director of A*STAR Infectious Diseases Labs and previously Senior Principal Investigator at SIgN, said: “We assessed the levels of immune mediators in these patients, which revealed several proinflammatory and activated T lymphocyte-associated cytokines sustained from infection to recovery phase. This correlated positively with CEC measure, implying cytokine-driven vessel damage. We found that COVID-19 patients with vascular complications have a higher frequency of T cells, which may in turn attack the blood vessels. Preventive therapy may be needed for these patients.”

Emphasising post- hospitalisation care for at-risk COVID-19 patients

The study's key findings can help inform guidelines for post-hospitalisation care of COVID-19 patients who might be susceptible to 'long-haul COVID' symptoms, said the research team.

In January this year, the World Health Organisation (WHO) released a recommendation in their revised clinical management guidelines, targeted at the risk of blood clot formation. For hospitalised patients, WHO recommended the use of low dose anticoagulants for preventing the blood clots forming in blood vessels.

Asst Prof Cheung added: "Those with cardiovascular conditions need to be more cautious since their underlying conditions already weaken their vascular systems. It's a double blow with COVID-19. As we gain greater understanding of complications COVID 'long-haulers' face, there is hope to encourage vaccine take-up rate to protect oneself from both the virus and its long-term complications."

Moving forward, the team is investigating the longer-term effects of COVID-19 in patients who have recovered from the infection for at least six months or longer.


Nanyang Technological University

Journal reference:

Chioh, F. W., et al. (2021) Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. eLife. doi.org/10.7554/eLife.64909.

Posted in: Medical Research News | Disease/Infection News

Tags: Blood, Blood Clot, Blood Vessel, Blood Vessels, Cytokine, Cytokines, Diabetes, Frequency, Heart, Heart Attack, Hospital, Immune Response, Immune System, Immunology, Infectious Diseases, Inflammation, Lymphocyte, Medicine, Research, Respiratory, Stroke, Vaccine, Vascular, Virus

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Surgery to correct congenital heart disease linked to increased risk of adult hypertension

In a medical records study covering thousands of children, a U.S.-Canadian team led by researchers at Johns Hopkins Medicine concludes that while surgery to correct congenital heart disease (CHD) within 10 years after birth may restore young hearts to healthy function, it also may be associated with an increased risk of hypertension — high blood pressure — within a few months or years after surgery.

Reporting their findings in the April 8, 2021, issue of JAMA Network Open, the researchers showed that children who had cardiac repair surgeries were 13 times more likely to develop hypertension as adults when compared with the general population.

"Congenital heart disease is among the most common forms of birth defects, and successful surgical interventions are usually performed before the age of 2; however, the specific risks of long-term, negative outcomes — including hypertension — are basically unknown for this population," says Chirag Parikh, M.D., Ph.D., director of the Division of Nephrology at the Johns Hopkins University School of Medicine and lead author of the new paper.

"So, we conducted what is believed to be the largest study with the longest follow-up ever of these children to better understand these risks and guide the development of methods to help them lessen the chance of hypertension-related cardiac disease or death," he says.

The hypertension study used the same data registry from a 2019 investigation of CHD repair and long-term risk of end-stage kidney disease.

Parikh says that clinical outcome studies in recent years provide evidence that surgical repair of heart problems during the first decade of life leaves behind some pathological changes that can continue in the cardiovascular system.

In an attempt to more precisely measure the problem of hypertension after childhood heart surgery, Parikh and his colleagues looked at medical records from seven linked Canadian patient databases. Since Canadians have universal access to health care services, the study population was less likely to have disparities and differences in the treatment and follow-up care they received.

From the list of all babies born in Ontario, Canada, between April 1, 2012, and March 31, 2015, the researchers selected 3,600 children who had surgeries to repair CHD within 10 years of birth, and matched them with 36,000 others who did not have the congenital condition nor any procedures performed on their hearts. The majority of the patients who had repair surgery were prematurely born males with low birth weights and around 150 days old at the time of their first surgery.

Cardiac repair surgeries performed on the patients were ranked from 1 to 4 in increasing complexity, with 43% being listed at categories 3 or 4 (the most complex), and including some even more complex than category 4. The two most commonly seen procedures (64%) were closure of a hole between the atria (upper chambers of the heart) or between the ventricles (lower chambers of the heart).

Both the cardiac repair surgery and the nonsurgery subjects were followed medically for up to 13 years, with data collected until death, diagnosis of hypertension or the end of the study (March 31, 2015). Of the 3,600 subjects who had surgery, 445 — or 12.4% — developed hypertension, compared with 398 out of 36,000 people — or 1.1% — who did not have the procedure. This means the children who had CHD repair surgery were 12 times more likely to become hypertensive.

The hypertension incidence rate — the total number of high blood pressure cases identified during the study period divided by the cumulative time in years for all of the patients participating (known as person-years) — also showed significantly higher risk of developing hypertension as an outcome of early age CHD repair surgery. For the surgery patients, the incident rate was 141.3 cases per 10,000 person-years compared with 11.1 cases per 10,000 person-years for those who did not have the surgery — a difference of nearly 13 to 1.

"We also saw that the more complex the cardiac surgery performed, the higher the risk for developing hypertension," Parikh says. "In the most extreme case, patients who had surgery to correct a hypoplastic left heart — a severe defect where the left side of the heart is underdeveloped — were three times more likely to develop hypertension than the congenital heart condition next in severity."

Other factors raising the risk of future hypertension were CHD repair surgery at age 3 months or younger, needing kidney dialysis during recovery from CHD repair surgery, and one or more cardiac surgeries after the initial repair.

Parikh cautions that medical records studies that "look back" at patient histories have limitations, but says that the research team's findings should be useful in guiding better long-term care for those at highest risk for hypertension, and subsequently, heart disease, stroke or kidney disease.

"For now, we recommend that children who have cardiac repair as infants be monitored more closely for hypertension throughout their lives," he says. "Future research will need to explore if early treatment of hypertension in these patients can prevent cardiovascular or renal problems later on."


Johns Hopkins Medicine

Journal reference:

Greenberg, J.H., et al. (2021) Long-term Risk of Hypertension After Surgical Repair of Congenital Heart Disease in Children. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2021.5237.

Posted in: Child Health News | Medical Procedure News | Medical Research News | Medical Condition News

Tags: Biopharmaceutical, Birth Defects, Blood, Blood Pressure, Cardiac Surgery, Children, Congenital Heart Defect, Congenital Heart Disease, Dialysis, Health Care, Heart, Heart Defect, Heart Disease, Heart Surgery, High Blood Pressure, Hospital, Hypoplastic, Kidney, Kidney Disease, Medicine, Nephrology, pH, Research, Stroke, Surgery

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Cardiologists recommend COVID-19 vaccine for heart patients


Because people with heart disease are likely to experience complications from COVID-19, Rush cardiologists are encouraging their patients to get the COVID-19 vaccine when they are eligible.

“I strongly recommend that everyone receive the COVID-19 vaccine,” says Joseph Mularczyk, MD, a cardiologist at Rush University Medical Center. “The vaccination is especially important for people who have prior heart issues because they are at significant risk of having a bad outcome from a COVID-19 infection.”

An increased risk

Even people who do not have heart disease and have had COVID-19 may experience long-term effects on heart health, including inflammation and damage to the heart muscle, Mularczyk says. But for those who already have heart disease, COVID-19 poses a higher risk of abnormal heart rhythms, heart failure and possible death. He says problems as basic as high blood pressure and vascular disease increase risk significantly.

“Generally speaking, patients who have cardiac conditions are at higher risk of complications from COVID-19,” says Gaurav Shah, DO, an interventional cardiologist at Rush Copley Medical Center. “COVID-19 predisposes patients to cardiac complications—such as heart attacks, irregular rhythms and weakened heart muscle—days and even weeks after a COVID-19 diagnosis.”

COVID-19 can affect the heart several ways. While the virus initially affects the respiratory system, Mularczyk explains the resulting decreased oxygen to the heart can lead to decreased heart function and damage.

In other instances, the heart muscle can be directly infected, or an inflammatory response can damage the heart muscle, disrupt the heartbeat, increase risk of clots forming in blood vessels and cause narrowing of blood vessels.

Preventing health complications

Edward Lipman, MD, an electrophysiologist at Rush Copley Medical Center, recommends the vaccine to his patients to help reduce their increased risk. Many of his patients have survived heart failure, had bypass surgery or other surgeries to replace or fix heart valves or put in stents, and gone through months of rehab. While they have already endured many health setbacks, he says the COVID-19 vaccine can help them prevent further heart and health complications.

Mularczyk notes that studies definitively show that the vaccine lowers a person’s risk of a bad outcome from COVID-19—especially for those who have heart conditions.

In addition to recommending the vaccine, the cardiologists encourage their patients and the public to continue to practice safety measures, even after vaccination.

“The most important thing you can do for your health is to wear a mask before and after getting a vaccine,” Lipman says.

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Depression risk higher among stroke survivors, especially female patients

Stroke patients were nearly 50% more likely than heart attack patients to develop depression, and female stroke patients had a higher risk of depression than their male counterparts, according to two preliminary studies by the same research group to be presented at the American Stroke Association's International Stroke Conference 2021.

The virtual meeting is March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

In what researchers described as one of the largest study of post-stroke depression to-date, they conducted two investigations using the same U.S. Medicare dataset of patients ages 65 or older hospitalized for ischemic stroke or heart attack from July 2016 to December 31, 2017.

Among more than 11 million Medicare beneficiaries who were admitted during the two-year study period, there were 174,901 with admission for ischemic stroke and 193,418 with admission for heart attack.

Patients were followed for 1.5 years, and patients with prior history of depression in the six months preceding their stroke or heart attack were excluded.

Depression following stroke is almost three times as common as it is in the general population and may affect up to a third of stroke patients. Patients with post-stroke depression also experience poorer quality of life and outcomes."

Laura K. Stein, M.D., M.P.H., Study Lead Author and Assistant Professor, Neurology, Icahn School of Medicine, Mount Sinai

Stein is also a attending neurologist at Mount Sinai and Mount Sinai Queens Stroke Centers in New York City.

In the first study (Presentation 22), researchers found:

  • The risk of depression was about 50% more likely among patients who had a stroke (174,901) compared to patients who had a heart attack (193,418).
  • History of anxiety was found in 10.3% of ischemic stroke patients and 11.8% of heart attack patients. Ischemic stroke patients with a history of anxiety were 1.7 times more likely to develop depression than patients without anxiety.
  • History of anxiety was the strongest predictor of post-stroke depression, while being discharged home resulted in less depression.
  • White patients were 1.33 times more likely to be diagnosed with post-stroke depression.
  • Patients 75 and older were 0.79 times less likely to be diagnosed with post-stroke depression.

"We did not expect that the cumulative risk of depression would remain so persistently elevated. This finding supports that post-stroke depression is not simply a transient consequence of difficulties adjusting to life after stroke," Stein said.

In another analysis by the same researchers (Presentation 21), female stroke patients (90,474) had a 20% higher risk of developing depression than male stroke patients (84,427).

Drawing from the same Medicare pool of patients, a comprehensive inpatient, outpatient and subacute nursing follow-up helped to detect new-onset depression more accurately compared to studies that don't have follow up from multiple settings where depression may be tracked.

Researchers calculated the increasing risk for depression in females vs. males over 1.5 years of follow-up. "Our current findings highlight the need for active screening and treatment for depression in the time period immediately and well after the stroke and the importance of screening all stroke patients for post-stroke depression, including women and those with a history of mental illness," Stein said.


American Heart Association

Posted in: Medical Research News | Medical Condition News | Women's Health News

Tags: Anxiety, Brain, Cerebrovascular Disease, Depression, Disability, Health Insurance, Heart, Heart Attack, Ischemic Stroke, Medicare, Medicine, Neurology, Nursing, Pathophysiology, Public Health, Research, Stroke

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First smart speaker for contactless monitoring of both regular and irregular heartbeats

Smart speakers, such as Amazon Echo and Google Home, have proven adept at monitoring certain health care issues at home. For example, researchers at the University of Washington have shown that these devices can detect cardiac arrests or monitor babies breathing.

But what about tracking something even smaller: the minute motion of individual heartbeats in a person sitting in front of a smart speaker?

UW researchers have developed a new skill for a smart speaker that for the first time monitors both regular and irregular heartbeats without physical contact. The system sends inaudible sounds from the speaker out into a room and, based on the way the sounds are reflected back to the speaker, it can identify and monitor individual heartbeats.

Because the heartbeat is such a tiny motion on the chest surface, the team's system uses machine learning to help the smart speaker locate signals from both regular and irregular heartbeats.

When the researchers tested this system on healthy participants and hospitalized cardiac patients, the smart speaker detected heartbeats that closely matched the beats detected by standard heartbeat monitors. The team published these findings March 9 in Communications Biology.

Regular heartbeats are easy enough to detect even if the signal is small, because you can look for a periodic pattern in the data. But irregular heartbeats are really challenging because there is no such pattern. I wasn't sure that it would be possible to detect them, so I was pleasantly surprised that our algorithms could identify irregular heartbeats during tests with cardiac patients."

Shyam Gollakota, Study Co-Senior Author and Associate Professor, Paul G. Allen School of Computer Science & Engineering, University of Washington

While many people are familiar with the concept of a heart rate, doctors are more interested in the assessment of heart rhythm. Heart rate is the average of heartbeats over time, whereas a heart rhythm describes the pattern of heartbeats.

For example, if a person has a heart rate of 60 beats per minute, they could have a regular heart rhythm — one beat every second — or an irregular heart rhythm — beats are randomly scattered across that minute but they still average out to 60 beats per minute.

"Heart rhythm disorders are actually more common than some other well-known heart conditions. Cardiac arrhythmias can cause major morbidities such as strokes, but can be highly unpredictable in occurrence, and thus difficult to diagnose," said co-senior author Dr. Arun Sridhar, assistant professor of cardiology at the UW School of Medicine. "Availability of a low-cost test that can be performed frequently and at the convenience of home can be a game-changer for certain patients in terms of early diagnosis and management."

The key to assessing heart rhythm lies in identifying the individual heartbeats. For this system, the search for heartbeats begins when a person sits within 1 to 2 feet in front of the smart speaker. Then the system plays an inaudible continuous sound, which bounces off the person and then returns to the speaker. Based on how the returned sound has changed, the system can isolate movements on the person — including the rise and fall of their chest as they breathe.

"The motion from someone's breathing is orders of magnitude larger on the chest wall than the motion from heartbeats, so that poses a pretty big challenge," said lead author Anran Wang, a doctoral student in the Allen School. "And the breathing signal is not regular so it's hard to simply filter it out. Using the fact that smart speakers have multiple microphones, we designed a new beam-forming algorithm to help the speakers find heartbeats."

The team designed what's called a self-supervised machine learning algorithm, which learns on the fly instead of from a training set. This algorithm combines signals from all of the smart speaker's multiple microphones to identify the elusive heartbeat signal.

"This is similar to how Alexa can always find my voice even if I'm playing a video or if there are multiple people talking in the room," Gollakota said. "When I say, 'Hey, Alexa,' the microphones are working together to find me in the room and listen to what I say next. That's basically what's happening here but with the heartbeat."

The heartbeat signals that the smart speaker detects don't look like the typical peaks that are commonly associated with traditional heartbeat monitors. The researchers used a second algorithm to segment the signal into individual heartbeats so that the system could extract what is known as the inter-beat interval, or the amount of time between two heartbeats.

"With this method, we are not getting the electric signal of the heart contracting. Instead we're seeing the vibrations on the skin when the heart beats," Wang said.

The researchers tested a prototype smart speaker running this system on two groups: 26 healthy participants and 24 hospitalized patients with a diversity of cardiac conditions, including atrial fibrillation and heart failure. The team compared the smart speaker's inter-beat interval with one from a standard heartbeat monitor. Of the nearly 12,300 heartbeats measured for the healthy participants, the smart speaker's median inter-beat interval was within 28 milliseconds of the standard monitor. The smart speaker performed almost as well with cardiac patients: of the more than 5,600 heartbeats measured, the median inter-beat interval was within 30 milliseconds of the standard.

Currently this system is set up for spot checks: If a person is concerned about their heart rhythm, they can sit in front of a smart speaker to get a reading. But the research team hopes that future versions could continuously monitor heartbeats while people are asleep, something that could help doctors diagnose conditions such as sleep apnea.

"If you have a device like this, you can monitor a patient on an extended basis and define patterns that are individualized for the patient. For example, we can figure out when arrhythmias are happening for each specific patient and then develop corresponding care plans that are tailored for when the patients actually need them," Sridhar said. "This is the future of cardiology. And the beauty of using these kinds of devices is that they are already in people's homes."


University of Washington

Posted in: Device / Technology News | Medical Science News | Healthcare News

Tags: Atrial Fibrillation, Breathing, Cardiology, Health Care, Heart, Heart Failure, Heart Rate, Machine Learning, Medicine, Research, Running, Skin, Sleep, Sleep Apnea

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Push is on for states to ban organ transplant discrimination

Griffin Dalrymple is an energetic 7-year-old who loves going to school in Eureka, Montana. But two years ago, the boy described by his mother, Jayci, as a "ball of fire" was suddenly knocked back by severe bacterial pneumonia that hospitalized him for two weeks.

As her son lay in the intensive care unit with a tube in his tiny lungs, Jayci began imagining worst-case scenarios. She worried that if Griffin ended up needing a lung transplant, he might be refused because he has Down syndrome.

"It was terrifying knowing that they could deny him certain lifesaving services," she said.

Denying organ transplants to people with intellectual and neurodevelopmental disabilities like Down syndrome or autism is common in the United States, even though it is illegal under the Americans with Disabilities Act.

According to one widely cited 2008 study, 44% of organ transplant centers said they would not add a child with some level of neurodevelopmental disability to the organ transplant list. Eighty-five percent might consider the disability as a factor in deciding whether to list the person.

After Griffin recovered, Jayci brought Montana lawmakers' attention to the issue. Largely as a result of her campaigning, the state is considering a bill that would ban physicians from denying an organ transplant based solely on a patient's disability. Last month, the bill — nicknamed "Griffin's Law" — passed the Montana Senate 50-0.

Although Montana has no transplant centers of its own, advocates hope this bill and others like it will draw attention to the issue and pressure physicians to examine why they are making certain decisions. Andrés Gallegos, chairman of the National Council on Disability, said he hopes such legislation will inspire "a change of heart so people understand that they are discriminating."

If the bill passes the state House and is signed by the governor, Montana would become the 17th state to ban such discrimination. Seven other states and the federal government have similar bills pending, although some experts doubt such laws will be enforceable enough to eliminate discrimination.

With more than 100,000 people on the waiting list for organs nationwide, and average wait times extending three to five years for some organs, physicians have to frequently make heart-rending decisions about which patients are likely to benefit most.

According to a 2019 report from the NCD, many physicians and organ transplant centers worry that patients with intellectual or neurodevelopmental disabilities are more likely to have co-occurring conditions that would make a transplant dangerous, or that these patients' quality of life is unlikely to improve with a transplant. Others believe that these patients may not be able to comply with post-transplant requirements, such as taking immunosuppressive drugs.

But the report, which scoured research papers and medical reports, found that none of these concerns is universally true. Rather, disabled patients can benefit as much as any other patient, according to the NCD, an independent federal agency.

"If a determination is made to not include a person on the list only because that individual has a disability, that's blatant discrimination," said Gallegos.

Many intellectually disabled patients and their families see this firsthand. When Joe Eitl was born in 1983 with a congenital heart defect, his mother, Peg, was told that Joe would never be a candidate for a new heart because of his Down syndrome. So, when his heart failed in 2019, eight hospitals refused to even consider a transplant for Joe, who lives with his mother in Philadelphia.

Peg Eitl conceded that Joe's case was difficult, given he'd had prior reconstructive heart surgery that would complicate a transplant. She pleaded with transplant centers for more than a year and even considered suing them. Last October, Vanderbilt University agreed to perform the procedure. Joe came home Feb. 10 and is recovering.

"I think my greatest frustration was the value placed on someone with special needs," Peg Eitl said. "It pains me that they’re discounted as being less than and not as worthy."

Bioethicist David Magnus of Stanford University, who authored the 2008 study on the extent of transplant discrimination, said people like Peg Eitl shouldn't have to prove that Joe would benefit from a transplant. Because people with disabilities are a protected class in the United States, he said, "the burden is on people who want to discriminate."

But that doesn't appear to be the case in practice. In September, Magnus published a follow-up survey of more than 300 transplant programs. Of these, 71% said they would automatically disqualify an adult with an IQ under 35, which is considered severe intellectual disability, while 12% would disqualify a child at that level. Only about 20% of the institutions had formal guidelines regarding child patients.

Magnus suspects these numbers are low given that some physicians may be unwilling to admit to discrimination. He has not yet studied whether new state laws have affected physicians' likelihood to discriminate against disabled patients.

But Magnus doubts that laws like Montana's bill will be enforceable. Part of determining any patient's eligibility for a transplant, he said, is whether they or a caretaker can comply with post-transplant requirements such as remembering to take immunosuppressant drugs. If a person with a disability can't meet these criteria, that person might not be a good candidate.

"All of these are terribly difficult judgments," Magnus said.

Transplant surgeons need to maximize the limited supply of organs and ensure they survive in the patients who receive them. If they don't, "it's taking an organ from someone who could have benefited from it," said Dr. Marwan Abouljoud, president of the American Society of Transplant Surgeons.

Abouljoud said institutions have differing standards for weighing the importance of an intellectual disability in a transplant decision. Ideally, he said, the committee that determines whether to list someone for a transplant will include social workers and behavioral psychologists, as well as program leadership, who can find ways to help the person comply.

On Feb. 12, the transplant surgeons' society adopted a new statement supporting nondiscrimination and encouraging transplant centers to find ways to support these patients. "We will be urging states to adopt local policies on this," Abouljoud said.

Sam Crane, legal director at the Autistic Self Advocacy Network, which has written model legislation adopted by several states, said that some bills — including Montana's — address the concern about post-transplant care. They ban transplant centers from basing their decision solely on a person's ability to carry out post-transplant requirements and require an investigation into sources of support to help the patient comply.

But Crane said physicians could still come up with a pretext to avoid adding a disabled person to the transplant list if they believe a person without a disability would benefit more from receiving an organ.

"It's very difficult to prove discrimination in that sort of situation," she said.

Although a similar nondiscrimination bill has been introduced in the U.S. House of Representatives, Crane said advocates prefer to focus on state laws. Organizations like the autism group have taken the position that the ADA and other federal laws already prohibit this kind of discrimination, making federal legislation unnecessary. Gallegos added that states can also enact stricter requirements than the federal government and fit them to their specific medical systems.

Under state laws, patients can appeal to local courts for an emergency injunction or restraining order. These hearings can be conducted quickly, allowing a judge to decide whether to compel an institution to add a person to the transplant list.

That speed is what Jayci Dalrymple hopes Griffin's Law will achieve. "When you're needing to stop discrimination, you’re racing the clock," she said.

This article was reprinted from khn.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente.

Posted in: Healthcare News

Tags: Autism, Congenital Heart Defect, Disability, Down Syndrome, Drugs, Healthcare, Heart, Heart Defect, Heart Surgery, Intensive Care, Kidney, Lung Transplant, Lungs, Organ Donation, Pneumonia, Public Health, Research, Surgery, Syndrome, Transplant

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