Physician-scientists at The Texas Heart Institute announced today the results of the largest cell therapy trial to date in patients with chronic heart failure due to low ejection fraction. The therapy benefited patients by improving the heart's pumping ability, as measured by ejection fraction, and reducing the risk of heart attack or stroke, especially in patients who have high levels of inflammation. Also, a strong signal was found in the reduction of cardiovascular death in patients treated with cells. The findings are published in the Journal of the American College of Cardiology.
Investigators in this landmark clinical trial have shown that a special immunomodulatory cell-type called MPC (mesenchymal precursor cells) developed by Mesoblast Inc., has the potential for the first time to address a major contributor to heart failure—inflammation. Patients in the trial were on full guideline-recommended drug therapy for heart failure, suggesting that the effect of the cell therapy was synergistic with and additive to state-of-the-art heart failure medications.
More than 6 million Americans have chronic heart failure, a progressive disease that leads to a weakening of the heart muscle and a loss of its pumping function. Most heart failure drugs used today are aimed at addressing the detrimental changes that occur in the heart as a result of complex neurohormonal pathways that are activated during heart failure to compensate for poor heart function.
These activated pathways eventually contribute to the progression of heart failure and repeated hospitalizations. Despite advances in therapies targeting these pathways, mortality rates remain high. The unique mechanism of action of MPC appears to provide an alternative approach that has the potential to make a significant impact on the high mortality of this disease.
More than six million Americans suffer from chronic heart failure, a disease that progressively weakens the heart’s muscle and destroys its ability to pump enough oxygen and blood to other organs.
However, results from the largest clinical trial of its kind offer hope to those with the disease, who up until now have relied largely on drugs that work on the heart’s complex neuralhormonal pathways but have done little to lower the mortality rate in time.
Physician-scientists at The Texas Heart Institute have shown that a new approach to heart failure, using cell therapy to combat one of the disease’s lead culprits – inflammation – can have a dramatic impact on the outcomes of sufferers.
In the phase 3 DREAM-HF trial, performed across 51 sites and involving 565 patients on medication for chronic heart failure, non-placebo recipients received a single transendocardial administration of mesenchymal precursor cells (MPC), then had a baseline and 12-month echocardiography performed.
Patients receiving the MPC cells, which were obtained from the bone marrow of healthy donors and developed by Australian biotech company Mesoblast, showed a significant strengthening of the left ventricular muscle and its pumping ability during that first 12 months. Thirty months on from the initial treatment, MPC therapy reduced the rate of heart attack or stroke by 58%, with this figure rising to 75% for those with high levels of an inflammation blood marker.
“The results of DREAM-HF are an important step in understanding how cell therapy provides benefits in patients with chronic heart failure due to poor pump function,” said Dr Emerson C. Perin, Medical Director at The Texas Heart Institute and the lead author of the study. “The cells appear to work by reducing inflammation, increasing microvascular flow, and strengthening heart muscle.”
When a heart stops beating, blood stops flowing and delivering oxygen to the brain (hypoxia) and other vital organs (ischemia). There is a small window (about 4 minutes) before the lack of blood flow begins to damage the brain. After 10 minutes, severe brain damage is expected. The sooner the heart can be restarted, the less the chances of severe brain injury.
Researchers at the Feinstein Institutes for Medical Research have tested a novel approach to increase survival rates, mitigate damage and accelerate repair in the ischemic brains of rats via mitochondrial transplantation. In a paper, "Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest," published in the journal BMC Medicine, the researchers detail the steps they took from in vitro lab to in vivo rat models in achieving a 91% survival rate—a 36% improvement over the control.
According to the endosymbiotic theory, mitochondria originated as a bacteria that "got swallowed" and forged a symbiotic relationship with the host cell, evolving into the mitochondria within the eukaryotic cells of complex lifeforms. Still, mitochondria have kept some of their ancient bacterial characteristics. They have double membranes like gram-negative bacteria and the ability to generate ATP with aerobic respiration—which requires oxygen—which is why our cells need oxygen deliveries from blood.
When blood stops flowing and oxygen delivery stops, mitochondria can no longer produce energy, and soon the cell is in danger of dying. If the blood has stopped flowing everywhere in the body the danger is everywhere, but nowhere more so than in the brain.
Mediterranean diet can cut heart disease risk in women by 24 percent, report says
Studies on the impact of a Mediterranean-type diet on heart disease have not often focused on women, the researchers say
By Ellen Francis
March 15, 2023 at 10:17 a.m. EDT https://www.washingtonpost.com/wellness ... men-study/
A Mediterranean diet could lower the risk of heart disease in women by 24 percent, new research says.
It’s the first such analysis of the possible link between a Mediterranean-type diet and cardiovascular disease that focuses on women, the authors say.
Heart disease is the leading cause of death globally, according to the World Health Organization, and in the United States, it is the No. 1 killer of women, the Centers for Disease Control and Prevention says.
Sanford Burnham Prebys researchers have identified a group of proteins that could be the secret to cellular reprogramming, an emerging approach in regenerative medicine in which scientists transform cells to repair damaged or injured body tissues. The researchers were able to reprogram damaged heart cells to repair heart injuries in mice following a heart attack. The findings, which appear in the journal Nature Communications, could one day transform the way we treat a variety of diseases, including cardiovascular disease, Parkinson's and neuromuscular diseases.
"Even if a person survives a heart attack, there could still be long-term damage to the heart that increases the risk of heart problems down the line," says lead author Alexandre Colas, Ph.D., an assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys. "Helping the heart heal after injury is an important medical need in its own right, but these findings also pave the way for wider applications of cell reprogramming in medicine."
Even though each of our cells has the same number of genes—approximately 20,000—cells can select which genes to "turn on" and "turn off" to change what they look like and what they do. This is the foundation of cellular reprogramming.
Heart failure is a global health problem commonly complicated by sleep apnea, a co-morbidity that further reduces a person’s lifespan. A promising new drug has been developed that could treat heart failure and sleep apnea by targeting the nervous activity that drives both.
For people with heart failure, the prognosis is poor and mortality high despite recent advances in treatment. According to the National Institutes of Health, heart failure affects more than 64 million people worldwide, making it a major global public health priority.
Heart failure occurs when the heart muscle weakens and doesn’t pump effectively. The brain responds to heart failure by activating the body’s sympathetic nervous system, the “fight or flight” response, to stimulate the heart to pump more effectively. However, long-term stimulation over the long term, combined with sleep apnea, leads to a reduced life expectancy. Most patients die within five years of a diagnosis of heart failure.
The part of the brain that sends impulses to the heart also controls breathing. Central sleep apnea (CSA) – where breathing repeatedly stops during sleep because the brain doesn’t send proper signals to the respiratory muscles – is common in people with heart failure. Sleep apnea is thought to be caused by increased sensitivity in the peripheral chemoreceptors found in the carotid arteries, which detect changes in arterial blood oxygen (hypoxia) and initiate reflexes to return oxygen levels to normal. One receptor in particular, P2X3, is known to affect this reflexive response.
The effects of a heart attack are often permanent, as the heart tissue cannot regenerate, unlike some other tissues.
This means that despite somebody surviving a heart attack, the damage done could cause health problems or death in the years following the event.
Regenerating heart tissue to allow damaged heart tissue to be treated is a hot topic in research.
Now researchers have discovered a mechanism that allows them to treat heart tissue in mice, before a heart attack, in a way that provides protection months later.
Although most people survive a heart attackTrusted Source initially, the risk of death significantly increases over the following years.
In fact, 65% of peopleTrusted Source who have a heart attack over the age of 65 die within eight years of the initial incident. This is at least partly because while a person may survive an initial heart attack, the heart attack itself, which leads to the heart tissue being deprived of oxygen and then dying, does not regenerate in adult humans.
In a recent animal study, researchers identified a mechanism that allowed them to treat heart tissue and make healthy mice’s hearts more resilient before a heart attack.
The study’s results appear in Nature Cardiovascular Research.
By University of Washington School of Medicine/UW Medicine April 9, 2023
Human Heart Anatomy
Researchers at the University of Washington School of Medicine have successfully engineered stem cells that do not cause dangerous arrhythmias, a major complication previously hindering stem-cell therapies for injured hearts. By using CRISPR-based genome editing to modify ion channels in the stem cells, the team created a new line of cells called “MEDUSA,” which engraft in the heart, mature, and integrate into heart muscle without generating dangerous heart rates.
Engineered stem cells do not provoke dangerous heart rhythms, a challenge that has prevented the progress of stem cell transplants for damaged hearts.
Researchers at the University of Washington School of Medicine in Seattle have successfully created stem cells that do not cause dangerous arrhythmias, a complication that has to date thwarted efforts to develop stem-cell therapies for injured hearts.
“We have found what we have to tackle to make these cells safe,” said Silvia Marchiano, a postdoctoral fellow in the laboratory of Chuck Murry at the UW Medicine Institute for Stem Cell and Regenerative Medicine. Marchiano is the lead author of a paper describing the findings published Thursday, April 6, in the journal Cell Stem Cell. The work was done in collaboration with the Seattle company Sana Biotechnology.
In earlier research, Murry’s team employed heart muscle cells derived from stem cells to mend heart tissue injuries resulting from myocardial infarction. This form of heart attack takes place when the blood supply to the cardiac muscle is obstructed, leading to the death of heart cells. Since cardiac cells do not regenerate, the damaged tissue is substituted by scar tissue. This compromises the heart’s strength and hinders its blood-pumping function. Extensive harm can culminate in heart failure and even death.
A new device designed to accurately and quickly sense whether a cardiac arrest patient also has a heart valve blockage that needs urgent treatment is now undergoing trials in Seattle.
Cardiologists and emergency physicians at Harborview Medical Center in Seattle are testing the Tropsensor, which has been designed to detect telltale troponin levels within 3-5 minutes of being fitted on the patient’s wrist.
Troponin, a protein found in the heart muscle, appears in the bloodstream when heart damage has occurred and an artery has been blocked, signifying a heart attack. Detecting this as early as possible in patients that have arrived at the ER allowed medical staff to treat this serious condition as quickly as possible.
Right now, triaging this condition involves an electrocardiogram (ECG), which can lack accuracy for those who have had a cardiac arrest, or a troponin blood test, which can cost an ill patient precious time waiting for pathology results.
“Early recognition of acute coronary occlusion could allow us to rapidly restore blood flow to the heart, which improves the short- and long-term outcomes for patients who have unrecognized heart attacks,” said Dr. Graham Nichol, an emergency physician at the University of Washington School of Medicine and director of Harborview’s Center for Prehospital Emergency Care.
A team of researchers led by Northwestern University and the University of Texas at Austin (UT) have developed a novel graphene heart implant that’s about the thickness of a strand of hair and monitors and corrects abnormal heart rhythms using light.
Heart rhythm disorders – cardiac arrhythmias – are caused by faulty electrical signaling in the heart, causing it to beat too quickly or too slowly. In some cases, this can lead to heart failure, stroke, and even sudden death.
Cardiac arrhythmias are commonly treated with implantable pacemakers and defibrillators, which monitor and correct abnormal rhythms. But these devices are inflexible and can constrain the heart, causing tissue injury and discomfort and increasing the risk of complications such as swelling, perforation, blood clots, and infection.
The new pacemaker is the first made from strong, lightweight, biocompatible ‘super material’ graphene and the thinnest to date. Unlike existing implantable pacemakers and defibrillators, this one molds itself to the heart tissue while being strong enough to withstand the rigors of a beating heart.
A new flexible, wearable medical device could provide a major boost in the fight against heart disease, the leading cause of death in the United States.
A team led by researchers at The University of Texas at Austin has developed an ultrathin, lightweight electronic tattoo, or e-tattoo, that attaches to the chest for continuous, mobile heart monitoring outside of a clinical setting. It includes two sensors that together provide a clear picture of heart health, giving clinicians a better chance to catch red flags for heart disease early.
"Most heart conditions are not very obvious. The damage is being done in the background and we don't even know it," said Nanshu Lu, a professor in the Department of Aerospace and Engineering Mechanics and a lead author of the study. "If we can have continuous, mobile monitoring at home, then we can do early diagnosis and treatment, and if that can be done, 80% of heart disease can be prevented."
The study is published in Advanced Electronic Materials.
As a continuation of an earlier chest e-tattoo project, this new version is wireless and mobile, which is enabled by a series of small active circuits and sensors carefully arranged and linked by stretchable interconnections and conforms to the chest via a medical dressing. The clear devices are far less intrusive than other monitoring systems and more comfortable for patients.
Currently, there isn't a ready solution for long-term, comfortable monitoring outside of the clinical setting. Clinicians can run tests on patients when they visit, but they may not catch some heart issues because signs of disease are not present at that moment.
Samsung Gets FDA Approval for Galaxy Watch AFib Detection
Soon, Samsung's Galaxy Watches will be able to monitor for dangerous heart activity in the background.
By Ryan Whitwam May 9, 2023
Samsung launched the Galaxy Watch 5 series last year with a suite of health sensors, including everything it needed to detect atrial fibrillation (AFib) like the Apple Watch. However, it wasn't allowed to do that until now. The Food and Drug Administration (FDA) has cleared Samsung to provide AFib monitoring on its current and upcoming wearables.
The way Samsung goes about detecting heart irregularities differs from Apple. The Apple Watch runs occasional heart rhythm checks and will report if anything seems amiss. Samsung's approach is more like Fitbit—the device takes continuous heart rate and rhythm readings and alerts the user after several anomalous measurements. Samsung calls this Irregular Heart Rhythm Notification (IHRN).
Machine learning algorithm a fast, accurate way of diagnosing heart attack
By Paul McClure
May 15, 2023
Heart attack symptoms are sometimes similar to non-heart-related conditions, making diagnosis tricky. UK researchers have turned to machine learning to provide doctors with a fast and accurate way of diagnosing heart attacks that has the potential to shorten the time needed to make a diagnosis and provide more efficient and effective treatment to patients.
Currently, the gold-star method for diagnosing a heart attack is to measure levels of the protein troponin in the blood. Troponin is released when the heart muscle is damaged; levels usually increase sharply within three to 12 hours after a heart attack, peaking after about 24 hours.
Many hospitals worldwide have adopted diagnostic pathways that include assessing troponin levels when someone is admitted with a suspected heart attack. But they have some limitations: they require the fixed-time collection of blood samples which can be a challenge in the emergency department setting; they only categorize patients as being a low, intermediate or high risk of a heart attack without considering other important information such as when the symptoms began or electrocardiogram (ECG) findings; and, they don’t take into account the influence of sex, age and comorbidities.
Now UK researchers have developed an AI-based machine learning algorithm that is fast and accurate. Named the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS), the algorithm was designed to calculate the probability of a heart attack for an individual patient.
An international research team led by the German University of Jena has now developed a promising approach to significantly reducing blood clotting on the heart valve material titanium.
Around 25,000 artificial heart valves are implanted in Germany per year because the original heart valve is damaged, for example, by an infection. The mechanical heart valves are made of titanium dioxide, among other materials, and last for many years. However, because blood tends to clot on contact with these material surfaces, there is a risk of blood clots forming on the surface of mechanical heart valves. This can become life-threatening if such blood clots break away from the materials. For this reason, most people with mechanical heart valves take medication throughout their lives to reduce blood clotting.
CT scans are better at predicting a middle-aged person's risk for a heart disease, such as a heart attack, than genetics, reports a new Northwestern Medicine study published May 23 in JAMA.
"Finding the best way to identify who is at risk for developing heart disease can help determine what needs to be done to lower their risk," said lead study author Dr. Sadiya Khan, an assistant professor of medicine and preventive medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine cardiologist. "This finding can help doctors and patients in managing risk for heart disease, which is the leading cause of death in the U.S."
Currently, conventional measures of risk-factor levels, such as blood pressure and cholesterol, are used by doctors to determine a person's likelihood of developing coronary heart disease or blockages of the arteries in the heart. But some people may experience a heart attack, or related heart problem, without one of those conventional factors picking it up.
Because the risk for heart disease can be inherited, scientists were optimistic that a person's genetics can inform who is at greatest risk, Khan said. It was posited that polygenic risk scores—a compilation of more than 6 million commonly occurring genetic variants associated with heart disease—could be used as a potential breakthrough for personalized medicine.
But the new Northwestern study directly compares genetics and CT scans for coronary artery calcium and demonstrates that the CT scan does a better job than genetics at predicting risk for heart disease in middle age.
"These findings support recommendations to consider CT screening to calculate risk for heart disease in middle-aged patients when their degree of risk is uncertain or in the intermediate range," Khan said.
Five subtypes of heart failure that could potentially be used to predict future risk for individual patients have been identified in a new study led by UCL researchers.
Heart failure is an umbrella term for when the heart is unable to pump blood around the body properly. Current ways of classifying heart failure do not accurately predict how the disease is likely to progress.
For the study, published in The Lancet Digital Health, researchers looked at detailed anonymized patient data from more than 300,000 people aged 30 years or older who were diagnosed with heart failure in the UK over a span of 20 years.
Using several machine learning methods, they identified five subtypes: early onset, late onset, atrial fibrillation related (atrial fibrillation is a condition causing an irregular heart rhythm), metabolic (linked to obesity but with a low rate of cardiovascular disease), and cardiometabolic (linked to obesity and cardiovascular disease).
Engineers at the University of California San Diego have developed a simple, low-cost clip that uses a smartphone's camera and flash to monitor blood pressure at the user's fingertip. The clip works with a custom smartphone app and currently costs about 80 cents to make. The researchers estimate that the cost could be as low as 10 cents apiece when manufactured at scale.
The technology was published May 29 in Scientific Reports.
Researchers say it could help make regular blood pressure monitoring easy, affordable and accessible to people in resource-poor communities. It could benefit older adults and pregnant women, for example, in managing conditions such as hypertension.
"We've created an inexpensive solution to lower the barrier to blood pressure monitoring," said study first author Yinan (Tom) Xuan, an electrical and computer engineering Ph.D. student at UC San Diego.
"Because of their low cost, these clips could be handed out to anyone who needs them but cannot go to a clinic regularly," said study senior author Edward Wang, a professor of electrical and computer engineering at UC San Diego and director of the Digital Health Lab. "A blood pressure monitoring clip could be given to you at your checkup, much like how you get a pack of floss and toothbrush at your dental visit."
Researchers at the UNC School of Medicine, UNC McAllister Heart Institute, and the UNC Lineberger Comprehensive Cancer Center characterized the expression of thousands of cardiac proteins during eight critical stages of embryonic heart development.
This research, published in Development Cell, will provide scientists with much-needed information to identify biological causes for congenital heart disease, or CHD.
"We now have a foundational data set that shows how protein dynamics change in normal heart development," said first author Whitney Edwards, Ph.D., and assistant professor in the UNC Department of Cell Biology and Physiology. "Researchers can use this as the blueprint to figure out the specific pathways or proteins contributing to congenital heart disease."
Ruxolitinib, a drug that is already approved by the U.S. Food and Drug Administration (FDA) for treating certain cancers and skin conditions, is effective at inhibiting CaMKII, a protein kinase linked to cardiac arrhythmias.
In a new study published June 21, 2023, in Science Translational Medicine, researchers from Johns Hopkins University and the University of Chicago invented a new reporting technique to monitor activity of CaMKII while screening the effects of nearly 5,000 FDA approved drugs on human cells that expressed the enzyme. The screen identified five previously unknown CaMKII inhibitors; ruxolitinib, which is used to treat cancers of the blood and bone marrow, along with skin conditions like atopic dermatitis and vitiligo, was the most effective.
CaMKII, or Calcium and calmodulin-dependent protein kinase II, is critical to cardiomyocytes, the muscle cells of the heart, where it maintains the balance of calcium. Activation of CaMKII helps facilitate rapid changes in heart activity, such as initiating a fight-or-flight response in the body. Overactivation can lead to impaired heart function and cell death, which can in turn lead to poor heart health outcomes like arrhythmia.
A new machine learning model uses electrocardiogram (ECG) readings to diagnose and classify heart attacks faster and more accurately than current approaches, according to a study led by University of Pittsburgh researchers that is published in Nature Medicine.
"When a patient comes into the hospital with chest pain, the first question we ask is whether the patient is having a heart attack or not. It seems like that should be straightforward, but when it's not clear from the ECG, it can take up to 24 hours to complete additional tests," said lead author Salah Al-Zaiti, Ph.D., R.N., associate professor in the Pitt School of Nursing and of emergency medicine and cardiology in the School of Medicine. "Our model helps address this major challenge by improving risk assessment so that patients can get appropriate care without delay."
Among the peaks and valleys of an ECG, clinicians can easily recognize a distinct pattern that indicates the worst type of heart attack called STEMI. These severe episodes are caused by total blockage of a coronary artery and require immediate intervention to restore blood flow.
The problem is that almost two-thirds of heart attacks are caused by severe blockage, but do not have the telltale ECG pattern. The new tool helps detect subtle clues in the ECG that are difficult for clinicians to spot and improves classification of patients with chest pain.