Tag: heart failure

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Why the Road for New Heart Cell Treatments is so Long

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Right side heart failure. Credit: Scientific Animations CC4.0

Pathways to new treatments for heart failure take time – as long as four decades for two now accepted therapies. So, new attempts to repair scar tissue in infarcted hearts using cells or cell products need more time to develop clinical therapies that can reduce risk of death from heart failure after a heart attack.

This message is part of a critical review of cell-based and cell product-based therapies for the treatment of heart failure. The review details 20 years of completed and ongoing clinical trials. While none has gained medical approval, they have proven safe and some have shown beneficial effects.

More importantly, the reviewers note, it took longer, nearly 40 years, to optimise two current therapies to reduce mortality in heart failure: implantable cardioverter–defibrillators and guideline-directed medical therapy.

“The history of the development of life-saving medical therapies for heart failure serves as an important lesson that we should remain hopeful of the promise of cell therapy in heart failure,” Jianyi “Jay” Zhang, MD, PhD, and colleagues write in the review, “Trials and tribulations of cell therapy for heart failure: an update on ongoing trials,” published in Nature Reviews Cardiology. Zhang is professor and chair of the University of Alabama at Birmingham Department of Biomedical Engineering.

Heart failure is responsible for 13% of deaths worldwide. Half of patients with heart failure die within five years. The most common cause of heart failure is blockage of coronary arteries leading to death of the cardiomyocyte heart muscle cells. When that muscle tissue is replaced by dense scar tissue with little blood circulation, the infarcted heart loses contractile power, leading to heart enlargement, progressive loss of pumping ability, increased chance of ventricular arrhythmias and clinical end-stage heart failure.

The problem is that shortly after birth, human heart muscle cells lose their ability to divide, so a damaged infarcted heart cannot repair itself by growing new muscle cells. Thus, the simple idea behind initial cell therapies was to add or inject replacement cells to the scar area to restore muscle tissue.

The two decades since has been a long road, with bumps and turns. The three parts of the Nature Reviews Cardiology paper describe the journey. 

First is a history of the slow development, obstacles, setbacks and scepticism for two current heart failure therapies, implantable cardioverter–defibrillators and guideline-directed medical therapy. The next two sections, and main focus of the review, survey 13 completed clinical trials published in the last 12 years and 10 very recently initiated and ongoing clinical trials that are based on the lessons learned from the past 20 years of research, to assess the safety and efficacy of cell- and cell products-based therapy approaches.

While several randomised, double-blind, multicentre phase II or III trials published in the past 20 years support the concept that even a single dose of cell products has beneficial effects in patients with heart failure on optimal medical therapy, the ongoing trial are taking novel directions, Zhang says. 

These include:

  • New cell types — pluripotent stem cell-derived cardiomyocytes/ spheroids and umbilical cord-derived mesenchymal stem cells
  • Repeated intravenous injections as a noninvasive cell delivery method
  • New cell products, such as engineered epicardial cardiomyocyte patches
  • Novel cell-free products — extracellular vesicle-enriched or exosome-enriched secretomes.

“The results of these trials will continue to define and refine our understanding of cell and cell product therapy as a novel addition in the treatment of patients with heart failure,” Zhang said. 

The review acknowledges scientific criticism during the slow but consistent progress and evolution of cell therapy. Some have questioned the use of public funding to support cell therapy research for heart failure treatment, due to poorly designed or underpowered clinical trials and very modest improvements in cardiac function in preclinical studies that are not always substantiated in large-scale clinical trials.

“These criticisms must be addressed in future trials that are adequately powered and rigorously designed to ensure continued progress of the field,” Zhang said. “Critique is an essential part of science, and the basis for growth, innovation and evolution – this is no less true for the field of cell therapy.” 

Yet Zhang is confident that current research will yield clinical translation. “In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration,” he said. “Cell therapy has encountered substantial barriers in both preclinical studies and clinical trials, but the field continues to progress and evolve through lessons learned from such research.”

Source: University of Alabama at Birmingham

Categories : Cardiovascular DiseaseTags :

Intermuscular Fat Raises the Risk of Heart Attack or Failure

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Photo by I Yunmai on Unsplash

People with intermuscular fat are at a higher risk of dying or being hospitalised from a heart attack or heart failure, regardless of their body mass index, according to research published in the European Heart Journal.

This intermuscular fat is highly prized in beef steaks for cooking but little is known about it in humans, and its impact on health. This is the first study to comprehensively investigate the effects of fatty muscles on heart disease.

The new finding adds evidence that existing measures, such as body mass index or waist circumference, are not adequate to evaluate the risk of heart disease accurately for all people.

The new study was led by Professor Viviany Taqueti, Director of the Cardiac Stress Laboratory at Brigham and Women’s Hospital and Faculty at Harvard Medical School, Boston, USA. She said: “Obesity is now one of the biggest global threats to cardiovascular health, yet body mass index – our main metric for defining obesity and thresholds for intervention – remains a controversial and flawed marker of cardiovascular prognosis. This is especially true in women, where high body mass index may reflect more ‘benign’ types of fat.

“Intermuscular fat can be found in most muscles in the body, but the amount of fat can vary widely between different people. In our research, we analyse muscle and different types of fat to understand how body composition can influence the small blood vessels or ‘microcirculation’ of the heart, as well as future risk of heart failure, heart attack and death.”

The new research included 669 people who were being evaluated at the Brigham and Women’s Hospital for chest pain and/or shortness of breath and found to have no evidence of obstructive coronary artery disease (where the arteries that supply the heart are becoming dangerously clogged). These patients had an average age of 63. The majority (70%) were female and almost half (46%) were non-white.

All the patients were tested with cardiac positron emission tomography/computed tomography (PET/CT) scanning to assess how well their hearts were functioning. Researchers also used CT scans to analyse each patient’s body composition, measuring the amounts and location of fat and muscle in a section of their torso.

To quantify the amount of fat stored within muscles, researchers calculated the ratio of intermuscular fat to total muscle plus fat, a measurement they called the fatty muscle fraction.

Patients were followed up for around six years and researchers recorded whether any patients died or were hospitalised for a heart attack or heart failure.

Researchers found that people with higher amounts of fat stored in their muscles were more likely to have damage to the tiny blood vessels that serve the heart (coronary microvascular dysfunction or CMD), and they were more likely to go on to die or be hospitalised for heart disease. For every 1% increase in fatty muscle fraction, there was a 2% increase in the risk of CMD and a 7% increased risk of future serious heart disease, regardless of other known risk factors and body mass index.

People who had high levels of intermuscular fat and evidence of CMD were at an especially high risk of death, heart attack and heart failure. In contrast, people with higher amounts of lean muscle had a lower risk. Fat stored under the skin (subcutaneous fat) did not increase the risk.

Professor Taqueti said: “Compared to subcutaneous fat, fat stored in muscles may be contributing to inflammation and altered glucose metabolism leading to insulin resistance and metabolic syndrome. In turn, these chronic insults can cause damage to blood vessels, including those that supply the heart, and the heart muscle itself.

“Knowing that intermuscular fat raises the risk of heart disease gives us another way to identify people who are at high risk, regardless of their body mass index. These findings could be particularly important for understanding the heart health effects of fat and muscle-modifying incretin-based therapies, including the new class of glucagon-like peptide-1 receptor agonists.

“What we don’t know yet is how we can lower the risk for people with fatty muscles. For example, we don’t know how treatments such as new weight-loss therapies affect fat in the muscles relative to fat elsewhere in the body, lean tissue, and ultimately the heart.”

Professor Taqueti and her team are assessing the impact of treatments strategies including exercise, nutrition, weight-loss drugs or surgery, on body composition and metabolic heart disease.

In an accompanying editorial, Dr Ranil de Silva from Imperial College London and colleagues said: “Obesity is a public health priority. Epidemiologic studies clearly show that obesity is associated with increased cardiovascular risk, though this relationship is complex.

“In this issue of the Journal, Souza and colleagues hypothesise that skeletal muscle quantity and quality associate with CMD and modify its effect on development of future adverse cardiovascular events independent of body mass index (BMI).

“In this patient population who were predominantly female and had a high rate of obesity, the main findings were that increasing levels of intermuscular adipose tissue (IMAT) were associated with a greater occurrence of CMD, and that the presence of both elevated IMAT and CMD was associated with the highest rate of future adverse cardiovascular events, with this effect being independent of BMI.

“The interesting results provided by Souza et al are hypothesis generating and should be interpreted in the context of several limitations. This is a retrospective observational study. Whilst a number of potential mechanisms are suggested to explain the relationship between elevated IMAT and impaired coronary flow reserve, these were not directly evaluated. In particular, no details of circulating inflammatory biomarkers, insulin resistance, endothelial function, diet, skeletal muscle physiology, or exercise performance were given.

“The data presented by Souza et al. are intriguing and importantly further highlight patients with CMD as a population of patients at increased clinical risk. Their work should stimulate further investigation into establishing the added value of markers of adiposity to conventional and emerging cardiac risk stratification in order to identify those patients who may benefit prognostically from targeted cardiometabolic interventions.”

Source: European Society of Cardiology

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

An Experimental Drug to Prevent Post-heart Attack Heart Failure

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Scientists at UCLA have developed a first-of-its-kind experimental therapy that has the potential to enhance heart repair following a heart attack, preventing the onset of heart failure. After a heart attack, the heart’s innate ability to regenerate is limited, causing the muscle to develop scars to maintain its structural integrity. This inflexible scar tissue, however, interferes with the heart’s ability to pump blood, leading to heart failure in many patients – 50% of whom do not survive beyond five years.

The new therapeutic approach aims to improve heart function after a heart attack by blocking a protein called ENPP1, which is responsible for increasing the inflammation and scar tissue formation that exacerbate heart damage. The findings, published in Cell Reports Medicine, could represent a major advance in post-heart attack treatment.

The research was led by senior author Dr Arjun Deb, a professor of medicine and molecular, cell and developmental biology at UCLA.

“Despite the prevalence of heart attacks, therapeutic options have stagnated over the last few decades,” said Deb, who is also a member of the UCLA Broad Stem Cell Research Center. “There are currently no medications specifically designed to make the heart heal or repair better after a heart attack.”

The experimental therapy uses a therapeutic monoclonal antibody engineered by Deb and his team. This targeted drug therapy is designed to mimic human antibodies and inhibit the activity of ENPP1, which Deb had previously established increases in the aftermath of a heart attack.

The researchers found that a single dose of the antibody significantly enhanced heart repair in mice, preventing extensive tissue damage, reducing scar tissue formation and improving cardiac function. Four weeks after a simulated heart attack, only 5% of animals that received the antibody developed severe heart failure, compared with 52% of animals in the control group.

This therapeutic approach could become the first to directly enhance tissue repair in the heart following a heart attack; an advantage over current therapies that focus on preventing further damage but not actively promoting healing. This can be attributed to the way the antibody is designed to target cellular cross-talk, benefitting multiple cell types in the heart, including heart muscle cells, the endothelial cells that form blood vessels, and fibroblasts, which contribute to scar formation. 

Initial findings from preclinical studies also show that the antibody therapy safely decreased scar tissue formation without increasing the risk of heart rupture – a common concern after a heart attack. However, Deb acknowledges that more work is needed to understand potential long-term effects of inhibiting ENPP1, including potential adverse effects on bone mass or bone calcification. 

Deb’s team is now preparing to move this therapy into clinical trials. The team plans to submit an Investigational New Drug, or IND, application to the U.S. Food and Drug Administration this winter with the goal of beginning first-in-human studies in early 2025. These studies will be designed to administer a single dose of the drug in eligible individuals soon after a heart attack, helping the heart repair itself in the critical initial days after the cardiac event.

While the current focus is on heart repair after heart attacks, Deb’s team is also exploring the potential for this therapy to aid in the repair of other vital organs.

“The mechanisms of tissue repair are broadly conserved across organs, so we are examining how this therapeutic might help in other instances of tissue injury,” said Deb, who is also the director of the UCLA Cardiovascular Research Theme at the David Geffen School of Medicine. “Based on its effect on heart repair, this could represent a new class of tissue repair-enhancing drugs.”

Categories : Cardiovascular Disease Regenerative MedicineTags :

Human Hearts may Possess a Latent Ability to Regenerate Cardiomyocytes

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Right side heart failure. Credit: Scientific Animations CC4.0

After severe heart failure, the ability of the heart to heal by forming new cells is very low. But now Karolinska Institutet researchers found that, after use of a supportive heart pump, the capacity of a damaged heart to repair itself with new cardiomyocytes becomes significantly higher – even greater than that of a healthy heart. This study is published in the journal Circulation.

The ability of the human heart to renew itself by regenerating its muscle cells, myocytes, is very limited. But what happens to this capability when the heart is damaged by severe heart failure has been unknown.

Researchers at Karolinska Institutet have now discovered that after an injury, the rate of cell renewal is even lower than in a healthy heart. Standard-of-care for patients with advanced heart failure is a surgically implanted pump that helps propel blood, a so-called left ventricular assist device (LVAD).

Kick-starting repair

Surprisingly, the researchers found that patients with such a heart pump, who have shown significant improvement in their heart function, can regenerate heart muscle cells at a rate more than six times higher than in healthy hearts.

“The results suggest that there might be a hidden key to kick-start the heart’s own repair mechanism”, says Olaf Bergmann, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and last author of the paper.

The mechanism behind the effect is still unknown and there is not yet any hypothesis to explain it.

“It is difficult to say. In the existing data we cannot find an explanation for the effect, but we will now continue to study this process at a cellular and molecular level,” says Olaf Bergmann.

The findings open the possibility of developing new therapies for patients with serious heart conditions that stimulate the heart’s ability to repair itself after damage. This way, patients wouldn’t have to rely only on heart transplants or other kinds of long-term mechanical support.

“This offers some hope that the recovery after a heart incident can somehow be boosted,” says Olaf Bergmann.

Atomic bombs enable cell age estimation

It is generally difficult to determine the age of cells in the human body and to decide which cells are new and which are old. However, by using a method earlier devised by Jonas Frisén, professor of stem cell research at Karolinska Institutet, the group has been able to count the rate of renewal of myocytes in the heart. The method is based upon the fact that the percentage of radioactive carbon in the atmosphere, and subsequently in our cells, has steadily decreased since the nuclear test ban in 1963. For every following year, there is a little less radioactivity in newly formed cells, which means that they can be ‘dated’. 

Source: Karolinska Institute

Categories : Cardiovascular DiseaseTags :

Tirzepatide Found to Protect against Worsening Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

The diabetes drug tirzepatide can reduce the risk of death or worsening heart failure for patients with heart failure, preserved heart pump function and obesity, new research from UVA Health reveals.

Researchers tested the GLP-1 receptor agonist in the SUMMIT clinical trial, where a total of 731 patients with diastolic heart failure and a body mass index (BMI) of 30 or above were randomised to receive injections of either tirzepatide or a harmless placebo. The researchers then followed the patients for a median period of two years. Tirzepatide is also prescribed as a weight loss drug in certain countries.

During that time, 56 placebo recipients died or suffered worsening heart failure, compared with only 36 of those receiving tirzepatide. Participants taking tirzepatide also lost 11.6% of their body weight.

“This class of drugs continue to show benefits far beyond weight loss,” said researcher Christopher Kramer, MD, chief of UVA Health’s Division of Cardiovascular Medicine. “This drug will become an important part of the armamentarium for patients with obesity-related heart failure and preserved heart function.”

Obesity and heart failure

Obesity is a major contributing factor to heart failure, so Kramer and his collaborators in the SUMMIT trial wanted to see if tirzepatide, a weight-loss drug already approved by the federal Food and Drug Administration, could help. 

The trial found that tirzepatide offered substantial benefits for managing diastolic heart failure, reducing deaths, preventing hospitalizations and generally benefiting recipients’ health and quality of life. For example, recipients saw improvements in how far they could walk in six minutes, as well as substantial decreases in a biological indictor used to measure inflammation and predict risk of serious cardiovascular events.

Side effects seen in the tirzepatide group consisted of gastrointestinal issues such as nausea and diarrhea, and these were mostly mild or moderate, the researchers reported Saturday at a meeting of the American Heart Association in Chicago.

Tirzepatide Findings

Kramer, a cardiovascular imager, also led a magnetic resonance imaging substudy looking at how tirzepatide affected recipients’ heart structure and function. The researchers found beneficial reductions in both left ventricular mass (weight of the heart) and in the amount of surrounding fat tissue. The reduction in LV mass correlated with the reduction in body weight, as well as with decreases in left ventricular volumes.

“This drug is reversing the abnormal properties of the heart brought on by obesity,” Kramer said. “There is much more to these drugs than weight loss alone.”

The findings from these studies by Kramer and his fellow researchers from SUMMIT are being published simultaneous with the American Heart meeting in Chicago in four separate manuscripts, including the New England Journal of Medicine, Nature Medicine, Circulation and the Journal of the American College of Cardiology.

Source: University of Virginia Health System

Categories : Cardiovascular Disease Mental HealthTags :

Beta Blockers may Also Cause Depression for Cardiac Patients

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Patients who have had a heart attack are typically treated using beta blockers. According to a Swedish study conducted earlier this year, this drug is unlikely to be needed for those heart patients who have a normal pumping ability. Now a sub-study at Uppsala University shows that there is also a risk that these patients will become depressed by the treatment.

“We found that beta blockers led to slightly higher levels of depression symptoms in patients who had had a heart attack but were not suffering from heart failure. At the same time, beta blockers have no life-sustaining function for this group of patients,” says Philip Leissner, a doctoral student in cardiac psychology and the study’s first author. The study was published in European Heart Journal Acute Cardiovascular Care.

Beta blockers are drugs that block the effects of adrenaline on the heart and have been used for decades as a basic treatment for all heart attack patients. In recent years, their importance has started to be questioned as new, successful treatments have begun to be developed. This is mainly the case for heart attack patients who do not suffer from heart failure.

The researchers wanted to look at the side effects of beta blockers, that is, whether they affect anxiety and depression levels. This is because older research and clinical experience suggests that beta blockers are linked to negative side effects such as depression, difficulty sleeping and nightmares.

Earlier this year, a major national study was conducted in Sweden, which found that those who received beta-blocking drugs were not protected from relapse or death compared to those who did not receive the drug. Leissner and his colleagues based their research on these findings and conducted a sub-study. It ran from 2018 to 2023 and involved 806 patients who had had a heart attack but no problems with heart failure. Half were given beta blockers and the other half were not. About 100 of the patients receiving beta blockers had been taking them since before the study, and the researchers observed more severe symptoms of depression in them.

“Most doctors used to give beta blockers even to patients without heart failure, but as the evidence in favour of doing so is no longer so strong, this should be reconsidered. We could see that some of these patients appear to be more at risk of depression. If the drug doesn’t make a difference to their heart, then they are taking it unnecessarily and at risk of becoming depressed,” adds Leissner.

Source: Uppsala University

Categories : Cardiovascular DiseaseTags :

Immunotherapy Blocks Scarring, Improves Cardiac Function in Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

A new study from Washington University School of Medicine in St. Louis suggests that a type of immunotherapy also may be an effective treatment strategy for heart failure by using an FDA-approved drug to block the signalling protein IL-1 beta. The study is published in Nature.

After a heart attack, viral infection or other injury to the heart, scar tissue often forms in the heart muscle, where it interferes with the heart’s normal contractions and plays a leading role in heart failure, a chronic condition which can only be slowed, not cured.

Studying human tissue samples as part of the new study, the researchers identified a type of fibroblast cell in the heart as the main culprit responsible for the formation of scar tissue in heart failure. To see if they could prevent scar formation, the scientists turned to mouse models of heart failure that have the very same type of fibroblasts. They used a therapeutic monoclonal antibody that blocks the formation of this harmful type of fibroblast, and succeeded in reducing the formation of scar tissue and improving heart function in the mice.

“After scar tissue forms in the heart, its ability to recover is dramatically impaired or impossible,” said cardiologist and senior author Kory Lavine, MD, PhD, a professor of medicine in the Cardiovascular Division at WashU Medicine. “Heart failure is a growing problem in the US and globally, affecting millions of people. Current treatments can help relieve symptoms and slow the progression, but there is a tremendous need for better therapies that actually stop the disease process and prevent the formation of new scar tissue that causes a loss of heart function. We are hopeful our study will lead to clinical trials investigating this immunotherapy strategy in heart failure patients.”

Fibroblasts have many roles in the heart, and parsing out the differences between various populations of these cells has been challenging. Some types of fibroblasts support the heart’s structural integrity and maintain good blood flow through the heart’s blood vessels, while others are responsible for driving inflammation and the development of scar tissue. Only recently, with the wide availability of the most advanced single cell sequencing technologies, could scientists peg which groups of cells are which.

“These various types of fibroblasts highlight newly recognised opportunities to craft treatment strategies that specifically block the type of fibroblasts that promote scarring and protect fibroblasts that maintain the structure of the heart, so the heart doesn’t rupture,” Lavine said. “Our research suggests that the fibroblasts that promote scarring in the injured heart are very similar to fibroblasts associated with cancer and other inflammatory processes. This opens the door to immunotherapies that potentially can stop the inflammation and resulting scar tissue.”

The research team, co-led by Junedh Amrute, a graduate student in Lavine’s lab, used genetic methods to demonstrate that a signaling molecule called IL-1 beta was important in a chain of events driving fibroblasts to create scar tissue in heart failure. With that in mind, they tested a mouse monoclonal antibody that blocks IL-1 beta and found beneficial effects in the mouse hearts. The mouse monoclonal antibody was provided by Amgen, whose scientists were also co-authors of the study. Monoclonal antibodies are proteins manufactured in the lab that modulate the immune system. The treatment reduced the formation of scar tissue and improved the pumping capacity of the mouse hearts, as measured on an echocardiogram.

At least two FDA-approved monoclonal antibodies, canakinumab and rilonacept, can block IL-1 signalling. These immunotherapies are approved to treat inflammatory disorders such as juvenile idiopathic arthritis and recurrent pericarditis, which is inflammation of the sac surrounding the heart.

One of these antibodies also has been evaluated in a clinical trial for atherosclerosis, a buildup of plaque that hardens the arteries. The trial, called CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), showed a benefit for study participants with atherosclerosis.

“Even though this trial was not designed to test this treatment in heart failure, there are hints in the data that the monoclonal antibody might be beneficial for patients with heart failure,” Lavine said. “Secondary analyses of the data from this trial showed that the treatment was associated with a sizable reduction in heart failure admissions compared with standard care. Our new study may help explain why.”

Even so, the IL-1 antibody used in the CANTOS study had some side effects, such as increased risk of infection, that could perhaps be reduced with a more targeted antibody that specifically blocks IL-1 signaling in cardiac fibroblasts, according to the researchers.

“We are hopeful that the combination of all of this evidence, including our work on the IL-1 beta pathway, will lead to the design of a clinical trial to specifically test the role of targeted immunotherapy in heart failure patients,” Lavine said.

Source: Washington University School of Medicine

Categories : Cardiovascular DiseaseTags :

A New Heart Failure Treatment Targets Abnormal Hormone Activity

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Right side heart failure. Credit: Scientific Animations CC4.0

Scientists have discovered a potential new treatment for heart failure with preserved ejection fraction (HFpEF), a type of heart disease that is notoriously difficult to treat. The diseased heart cells were found to have high levels of glucagon activity, a pancreatic hormone that raises blood glucose levels. The scientists then demonstrated that a drug that blocks the hormone’s activity can significantly improve heart function.

In heart failure, which is considered a global pandemic, the heart can no longer pump blood effectively. Globally, an estimated 64 million people live with this condition with HFpEF accounting for around half of the cases.

In HFpEF, the heart can pump normally but its muscles are too stiff to relax to re-fill the chambers with blood properly. It is often seen in older adults and people with multiple risk factors including high blood pressure (hypertension), obesity and diabetes. They typically have symptoms such as shortness of breath, fatigue and reduced ability to exercise. This is unlike heart failure with reduced ejection fraction (HFrEF), where heart muscle is weakened and pumping volume reduced.

There have been studies on how the heart is stressed by hypertension and metabolic diseases associated with obesity, such as diabetes, but these have been done in isolation of each other. This latest study, which was published in Circulation Research, addresses this gap by taking into account both stressors, revealing for the first time, the molecular pathway that contributes to HFpEF progression.

In pre-clinical studies, the team of scientists, which included collaborators from the University of Cincinnati College of Medicine, University of California Los Angeles, University of Toronto and University of North Carolina School of Medicine, investigated how stress from hypertension affected lean hearts versus diabetic/obese ones. In their findings, the lean models developed heart failure with reduced ejection fraction (HFrEF), typically observed in hypertensive patients. The obese models however, developed heart failure with preserved ejection fraction (HFpEF), proving that a combination of stressors give rise to the disease and providing a good model for further studies.

Using advanced single-cell RNA-sequencing technologies, the scientists were then able to study the expression of every detected gene in every single heart cell, allowing them to uncover specific genetic variations in cells associated with HFpEF. The scientists found that in the obese models, the most active genes were the ones driving the activity of glucagon.

Professor Wang Yibin, Director of the Cardiovascular & Metabolic Disorders Programme at Duke-NUS and senior author of the study, said:

“Under stress conditions such as high blood pressure and metabolic disorders like obesity and diabetes, we found that glucagon signalling becomes excessively active in heart cells. This heightened activity contributes to the development of heart failure with preserved ejection fraction (HFpEF) by increasing heart stiffness and impairing its ability to relax and fill with blood.”

The team then tested a drug that blocks the glucagon receptor in a pre-clinical model of HFpEF and found significant improvements in heart function, including reduced heart stiffness, enhanced relaxation, improved blood filling capacity and overall better heart performance.

Assistant Professor Chen Gao from the Department of Pharmacology, Physiology and Neurobiology at the University of Cincinnati College of Medicine; and the study’s first author, said:

“Our study shows strong evidence that a glucagon receptor blocker could work well to treat HFpEF. Repurposing this drug, which is already being tested in clinical trials for diabetes, could bypass the lengthy drug development process and provide quicker and more effective relief to millions of heart patients.”

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, commented:

“With our ageing population, there will likely be more patients with multiple conditions, including heart failure, diabetes and hypertension, presenting a significant challenge to health systems. Uncovering the synergistic impact of such illnesses and their underlying mechanisms is key to better understanding the complex process of heart failure and developing an effective treatment for the disease.”  

The researchers hope to work with clinical partners to conduct clinical trials to test the glucagon receptor blocker in humans with HFpEF. If these succeed, it could become one of the first effective treatments for this challenging condition, significantly improving the quality of life for millions worldwide.

Source: Duke University

Categories : Cardiovascular DiseaseTags :

SA Heart Congress Unites Cardiologists for Better Care

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The SA Heart Annual Congress will take place from 8–10 November at the Sandton Convention Centre, Johannesburg. The three-day Congress, themed ‘Cardiology Connections,’ will promote collaboration and dialogue among local and international Cardiology professionals. The congress offers a unique platform for experts, practitioners, and researchers worldwide to share insights on the latest advancements and challenges in cardiovascular medicine.

The dynamic programme includes keynote speeches, panel discussions, workshops, and networking sessions. The agenda covers a comprehensive range of cardiology topics, designed to provide practical knowledge and inspire innovation in the field. Attendees will gain critical insights into the latest developments that have the potential to enhance patient care.

“We are excited to welcome a distinguished international and local faculty,” says Dr Ahmed Vachiat, SA Heart Congress Convenor. “At the core of SA Heart is the mission to advance cardiovascular care through education, research, and advocacy. By connecting healthcare professionals from across sectors, this Congress will drive forward our vision of improving cardiovascular care for all in South Africa. We are also grateful for the invaluable support of our local experts, whose contributions consistently uphold international standards of excellence.”

A significant focus this year is strengthening connections among various special interest groups, including the Society of Cardiovascular Interventions (SASCI), Cardiovascular Imaging Society of South Africa (CISSA), Cardiovascular Arrhythmia Society of South Africa (CASSA), Heart Failure Association of South Africa (HEFFSA), Intervention Society of Cardiovascular Allied Professionals (ISCAP), South African Society of Cardiovascular Research (SASCAR), and the Paediatric Society of Cardiology (PCSSA).

Joint sessions and interdisciplinary programmes will enable these groups to work together to enhance healthcare delivery for all patients in need of cardiac intervention and treatment. Workshops and scientific sessions will feature innovative learning approaches aimed at facilitating knowledge exchange and professional growth.

A cardiovascular team from the Mayo Clinic – Prof Vuyi Nkomo (Imaging Cardiologist), Prof Sorin Pislaru (Chair, Structural Heart Disease), and Dr Juan Crestanello (Chair, Cardiothoracic Surgery) – will conduct an echocardiography workshop and contribute to various specialist workshops on Friday morning, November 8th.

Dr Thomas Alexander, a respected interventional cardiologist based in India, will share insights on establishing STEMI networks in South Africa. Prof Stylianos Pyxaras from Germany and Dr Andrew Ludwiniec from the UK will discuss chronic total occlusions and complex coronary interventions. Prof Azfar Zaman and Prof Roy Gardner also from the UK and leaders in their field, as well as Prof Thierry Lefevre from France, will join esteemed local experts in addressing important cardiovascular topics.

A new addition to this year’s programme is the Imbizo on Rheumatology and Cardiac diseases. Over 40 Abstracts have been submitted and research sessions guided by SASCAR will be keeping delegates up to date with the latest in the field of Cardiology.

In addition, an excellent parallel paediatric programme will feature global leaders, Prof Krishna Kumar, from India and Prof McDaniel from the USA, with a pre-congress workshop and highly interactive sessions that will incorporate insights from local experts.

“This year, a Heartbeat Stage will feature insightful talks, engaging presentations, and a special networking address,” says Dr Vachiat. “We are honoured to have Dr Imtiaz Sooliman from Gift of the Givers, who will share his thoughts on ‘Connecting Hearts and Social Responsibility’.”

For more information, visit SA Heart.

Categories : Cardiovascular DiseaseTags :

Finerenone Reduces Worsening Heart Failure and Cardiovascular Death in Clinical Trial

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Right side heart failure. Credit: Scientific Animations CC4.0

Finerenone reduced the composite of total first and recurrent heart failure (HF) events (hospitalisations for HF or urgent HF visits) and cardiovascular death in patients with HF and mildly reduced or preserved ejection fraction, according to an international clinical trial led by investigators from Brigham and Women’s Hospital.

Heart failure events and cardiovascular death were less common in the finerenone group than in the placebo group. Overall, the rate of serious adverse events was similar across the groups, but rates of hyperkalaemia were higher for the group taking finerenone. Results were presented at the European Society of Cardiology Congress 2024 and published simultaneously in the New England Journal of Medicine.

“We saw benefit regardless of the ejection fraction and even in patients who were on other approved therapies,” said trial principal investigator and corresponding author Scott Solomon, MD, the director of the Clinical Trials Outcomes Center at Mass General Brigham and the Edward D. Frohlich Distinguished Chair at Brigham and Women’s Hospital. “This drug represents a new drug class that may become a pillar of therapy for this disease.”

HF is the progressive decline in the heart’s ability to fill with and pump blood. It affects over 60 million people worldwide. Approximately half of all people living with HF have mildly reduced or preserved left ventricular ejection fraction, a condition with limited treatment options. These findings suggest that the non-steroidal mineralocorticoid receptor antagonist finerenone could represent a new therapeutic option for patients.

The FINEARTS-HF trial, funded by Bayer, assigned 6000 patients to receive either finerenone or placebo in addition to their existing therapies. The trial’s limitations include few Black patients, although the percentage of Black patients was proportional to their regional population. “Our group continues to study novel therapies for heart failure,” Solomon said. “There’s huge residual risk in these patients and so more room for new therapies.“

Source: Brigham and Women’s Hospital