Category: Cardiovascular Disease

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New Treatment Resistant Blood-clotting Disorder Identified

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Thrombophilia. Credit: Scientific Animations CC4.0.

Researchers at McMaster University have made a groundbreaking discovery in the field of haematology, providing an explanation for spontaneous and unusual blood-clotting that continues to occur despite treatment with full-dose blood thinners.

The discovery, published in The New England Journal of Medicine, is expected to influence how doctors test for, and treat patients with, unusual or recurrent blood clotting, with the potential to improve patient outcomes.

Researchers found this new blood clotting disorder to have certain similarities to vaccine-induced immune thrombocytopenia and thrombosis (VITT) – a rare but aggressive clotting disorder that was caused by certain discontinued COVID-19 vaccines.

The research reveals that certain patients can develop severe blood clotting due to antibodies that closely resemble those that cause VITT, even in the absence of known triggers for such antibodies, such as blood thinners (heparin) or prior vaccination.

The newly identified disorder has been termed VITT-like monoclonal gammopathy of thrombotic significance (MGTS).

“Our study highlights the importance of recognising and diagnosing this new blood-clotting disorder,” said Theodore (Ted) Warkentin, co-first author and corresponding author of the study and professor emeritus in the Department of Pathology & Molecular Medicine at McMaster University.

“By understanding how to diagnose VITT-like MGTS, we can develop more effective treatment strategies that go beyond traditional anticoagulation,” said Warkentin, a hematologist in the Department of Medicine based at Hamilton Health Sciences’ Hamilton General Hospital.

Specialized testing was conducted at the McMaster Platelet Immunology Laboratory within the Michael G. DeGroote Centre for Transfusion Research, the only laboratory in Canada with the full repertoire of testing required to characterize the VITT-like antibodies that target the PF4 protein. Researchers performed a detailed analysis of cases exhibiting unusual blood-clotting despite patients being on full-dose blood thinners, focusing on those patients who had unexplained VITT-like antibodies that were detectable for a year or more.

The analyses identified the presence of M (monoclonal) proteins (which typically indicate plasma cell disorders), and together with the persisting VITT-like reactivities over at least 12 months (which is highly unusual for most anti-PF4 antibodies), thus pointing to an ongoing pathological process rather than a short-term anomaly.

The study included a multinational collaboration, with data collected from five patients treated at institutions in Canada, New Zealand, France, Spain, and Germany.

Collaborator Jing Jing Wang of Flinders University in Australia played a crucial role in proving for each patient that the M proteins are the pathological VITT-like antibodies. Collaborator Andreas Greinacher of Greifswald University in Germany helped in identifying similar cases in his anti-PF4 reference lab.

“The findings of this study underscore our ability to leverage fundamental molecular and biochemical science to unravel disease mechanisms,” said Ishac Nazy, co-lead author of the study and scientific director of the McMaster Platelet Immunology Laboratory and co-director of the Michael G. DeGroote Centre for Transfusion Medicine.

“This approach enables precise patient diagnosis and informs timely treatment strategies, even for previously unidentified diseases, exemplifying true bench-to-bedside translational medicine,” said Nazy, associate professor in the Department of Medicine at McMaster.

A remarkable observation was that each of the patients had failed blood thinning treatment, but they showed some benefit with unusual treatments, such as high-dose intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and plasma cell–targeted myeloma therapy. The existence of this novel blood clotting disorder has important implications for how health care providers will evaluate patients who develop unusual or difficult to treat blood clots in the future.

Source: McMaster University

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Mechanical Heart Valve Replacements have Better Long-term Survival

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Artificial heart valve. Credit: Scientific Animations CC4.0

Patients aged between 50 to 70 years with a mechanical heart valve replacement had better long-term survival compared to those with a biological valve, new research led by the University of Bristol has found. The study is published in the European Journal of Cardio-Thoracic Surgery.

The last two decades have seen an increase in the use of biological over mechanical heart valve replacements. However, while short-term clinical outcomes are known to be the same, long-term outcomes are still under debate.

Existing guidelines support the use of mechanical valves made of synthetic materials in patients below the age of 50, while biological valves made of animal tissue are favoured for those above the age of 65 or 70. The guidelines leave the choice to the decision of surgeons and patients who are 50 to 70 years old.

The research team wanted to find out the clinical outcomes for patients aged between 50 to 70 years undergoing elective and urgent heart valve replacement at the Bristol Heart Institute (BHI) over a 27 year period [1996 to 2023].

The researchers also sought to investigate trends, early outcomes and long-term survival rates, the incidence of repeat valve interventions and patient prosthesis mismatch (PPM).

A total of 1708 (61% male) patients with an average age of 63 years were included with 1191 (69.7%) receiving a biological valve replacement.

The research found there were no short-term differences when comparing patients receiving biological and mechanical valves. However, patients who received mechanical valves had better long-term survival up to 13 years after having surgery. 

Patients with a size 19mm biological valve replacement (a fairly small valve commonly used in females) had the worse long-term survival. Patients with a size 21mm mechanical valve had better survival compared to both size 19 and 21mm biological valves.  The study confirmed that severe PPM is a significant risk factor for poor long-term survival.

Gianni Angelini, BHF Professor of Cardiac Surgery at the Bristol Medical School: Translational Health Sciences (THS), Director of the Bristol Heart Institute and corresponding author, said: “Our study has implications for decision-making in surgical heart valve replacements for patients aged between 50 and 70 years old. The evidence supporting better long-term survival in patients receiving a mechanical heart valve suggests the current trend favouring biological valves in this age bracket should be urgently reconsidered. The survival benefit is especially clear in smaller sized valves.”

The research team recommends the evaluation of the long-term benefits associated with mechanical valves, especially in smaller sizes, despite long-term blood thinners not being needed with biological valves.

Study limitations

The single-institution design, retrospective collection of data, and absence of randomisation make the study open to bias. The lack of echocardiographic information could potentially underestimate the incidence of structural valve failure. In terms of repeat valve interventions, only patients who underwent re-do surgical aortic valve replacement or valve in valve transcatheter aortic valve implantation (TAVI) at the BHI were included.

As the BHI is a supra-regional centre, it is very unlikely that many patients might have undergone reintervention in other institutions. The cause of  death (cardiovascular/non cardiovascular) was not available.

Source: University of Bristol

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Study Probes How to Predict Complications from Preeclampsia

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Data from 8843 women diagnosed with preeclampsia during pregnancy showed that existing risk prediction models are most accurate only in the days after diagnosis

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The existing prediction models for severe complications of preeclampsia are most accurate only in the two days after hospital admission, with deteriorating performance over time, according to a new study published February 4th in the open-access journal PLOS Medicine by Henk Groen of University of Groningen, the Netherlands, and colleagues.

Preeclampsia is a potentially life-threatening condition that can occur during pregnancy; of women diagnosed with preeclampsia, 5-20% will develop severe complications. Two existing PIERS (Pre-eclampsia Integrated Estimate of RiSk) models, PIERS Machine Learning (PIERS-ML) and the logistic-regression-based fullPIERS, are designed to identify individuals at greatest or least risk of adverse maternal outcomes in the 48 hours following hospital admission for preeclampsia. However, both models are regularly used for ongoing assessment beyond the first 48 hours.

In the new study, researchers used data from 8843 women diagnosed with preeclampsia at a median gestational age of 36 weeks between 2003 and 2016. Data included PIERS-ML and fullPIERS assessments as well as health outcomes.

The study found that neither the PIERS-ML nor fullPIERS model maintained good performance over time for repeated risk stratification in women with preeclampsia. The PIERS-ML remained generally good at identifying the very high-risk and very-low risk groups over time, but performance of the larger high-risk and low-risk groups deteriorated significantly after 48 hours. The fullPIERS model underperformed compared to the PIERS-ML model.

“Since there are no better options, clinicians may still use these two models for ongoing assessments after the first admission with pre-eclampsia, but the predictions should be treated with increasing caution as the pregnancy progresses,” the authors say. More prediction models are needed that perform well over time, they add.

The authors add, “Pregnancy hypertension outcome prediction models were designed and validated for initial assessment of risks for mothers; this study shows that such ‘static’ models if used repeatedly over days yield increasingly inaccurate predictions.”

Provided by PLOS

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Born to Heal: Why Babies Recover, but Adults scar, After Heart Damage

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Photo by William Fortunato on Pexels

Newborns with heart complications can rely on their newly developed immune systems to regenerate cardiac tissues, but adults aren’t so lucky. After a heart attack, most adults struggle to regenerate healthy heart tissue, leading to scar-tissue buildup and, often, heart failure.

A new Northwestern Medicine study in experimental animals reveals a critical difference in how macrophages help repair the heart in newborns versus adults after a heart attack. The study highlights a fundamental difference in how the immune system drives healing based on age.

The study appears in the journal Immunity.

“Understanding why newborns can regenerate their hearts while adults cannot will open the door to developing treatments that could ‘reprogram’ adult macrophages,” said first and co-corresponding author Connor Lantz, lead scientist of the bioinformatics core at the Comprehensive Transplant Center at Northwestern University Feinberg School of Medicine.

In newborns, macrophages perform a process called efferocytosis, which recognizes and eats dying cells. This process triggers the production of a bioactive lipid called thromboxane, signaling nearby heart muscle cells to divide, and allowing the heart to regenerate damaged heart muscle, the study found. In adults, macrophages produce much less thromboxane, leading to a weaker repair signal.

“By mimicking the effects of thromboxane, we might one day improve tissue repair after a heart attack in adults,” Lantz said.

How the study worked

The study examined how the immune system responds to heart injury in mice of different ages, including newborn mice (one day old) and adult mice (eight weeks old). The researchers found the ability of macrophages to engulf dying cells was enhanced in newborn mice due to increased expression of MerTK, a receptor that recognizes dying cells. Therefore, when the scientists blocked this key receptor, newborn mice lost their ability to regenerate their hearts, resembling adult hearts after a heart attack.

Engulfment of dying cells by newborn macrophages triggered a chemical chain reaction that produced a molecule called thromboxane A2, which unexpectedly stimulated heart muscle cells to multiply and repair the damage, the study found. Additionally, nearby muscle heart cells in newborns are primed to respond to thromboxane A2, leading them to change their metabolism to support their growth and healing. But in adults, this process did not work the same way – after an injury, their macrophages did not produce enough thromboxane A2, limiting their ability to regenerate heart tissue.

Source: Northwestern University

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New Treatment Offers a Quick Cure for Common Cause of Hypertension

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Credit: Pixabay CC0

Doctors at Queen Mary University of London, Barts Health NHS Trust and University College London have developed a groundbreaking, minimally invasive treatment, Triple T, offering hope for millions of people with high blood pressure caused by a commonly overlooked condition. 

The treatment, which could transform blood pressure management, has been published in The Lancet.

Triple T, also known as endoscopic ultrasound-guided radiofrequency ablation, is poised to change the way we address primary aldosteronism (PA) – a hormonal disorder that causes high blood pressure in one in 20 patients with blood pressure yet is often undiagnosed and untreated. This treatment has shown promising results in clinical trials and could become an accessible alternative to surgery, offering relief to those who suffer from this condition. 

The hidden cause of high blood pressure  

High blood pressure, affecting one in three adults, has several underlying causes, with PA being one of the most common yet underdiagnosed. In this condition, benign nodules in the adrenal glands produce excess aldosterone, a hormone that raises blood pressure by increasing salt levels in the body. Patients with PA often do not respond to standard medications and face increased risks of heart attacks, strokes and kidney failure. 

Until now, the only effective treatment for PA has been the surgical removal of the affected adrenal gland. However, this procedure requires general anaesthesia, a hospital stay, and weeks of recovery, causing many patients to go untreated. Triple T provides a faster, safer, and less invasive alternative by targeting and destroying the malfunctioning adrenal nodule without removing the gland.  

How Triple T works 

The procedure uses a combination of radiofrequency or microwaves and ultrasound to deliver targeted heat to the adrenal nodule. A fine needle is inserted through the stomach to the adrenal gland, guided by real-time ultrasound imaging, where short bursts of heat are used to destroy the problematic tissue. This targeted approach ensures minimal damage to surrounding healthy tissues. The entire procedure lasts only 20 minutes and requires no incision.   

Triple T’s success stems from recent advances in diagnostic scans, which use molecular dyes to accurately locate even the smallest adrenal nodules. These breakthroughs, combines with the ability to directly target nodules adjacent to the stomach, have enabled this minimally invasive approach. 

Successful trial and promising results  

The Feasibility study of radiofrequency endoscopic ABlation, with ULtrasound guidance (FABULAS) trial which tested Triple T on 28 patients with PA, showed excellent results. The procedure was found to be safe and effective, with most patients experiencing normalised hormones levels within six months. Many participants were able to stop all blood pressure medications, and the condition did not recur. 

Professor Morris Brown, co-senior author of the study and Professor of Endocrine Hypertension at Queen Mary University of London, reflected on the significance of this milestone: “It is 70 years since the discovery in London of the hormone aldosterone, and, a year later, of the first patient in USA with severe hypertension due to an aldosterone-producing tumour. This patient’s doctor, Jerome Conn, predicted, with perhaps only minor exaggeration, that 10-20% of all hypertensions might one day be traced to curable nodules in one or both glands. We are now able to realise this prospect, offering 21st-century breakthroughs in diagnosis and treatment.”  

One trial participant, Michelina Alfieri, shared her experience: “Before the study, I suffered from debilitating headaches for years despite multiple GP visits. As a full-time worker and single parent, my daily life was severely affected. This non-invasive treatment provided an immediate recovery—I was back to my normal routine straight away. I’m incredibly grateful to the team for giving me this choice.”  

What’s next?  

The success of the FABULAs trial has led to a larger study, WAVE, which will compare Triple T with traditional surgery in 120 patients. Results are expected in 2027. 

Professor Stephen Pereira, Chief Investigator of FABULAS, emphasised the potential global impact of Triple T. he said: “This less invasive technique could be widely offered in endoscopy units across the UK and internationally.”  

Clinical Endocrinology Lead at Addenbrooke’s Hospital and Professor of Clinical Endocrinology at the University of Cambridge, Professor Mark Gurnell, said: “Thanks to this work, we may finally be able to diagnose and treat more people with primary aldosteronism, lowering their risk of developing cardiovascular diseases and other complications, and reducing the number of people dependent on long-term blood pressure medication.” 

The research was primarily supported by Barts Charity, National Institute for Health and Care Research (NIHR) through the Barts and Cambridge Biomedical Research Centres (BRCs), and the British Heart Foundation.  

It is being followed by a larger randomised trial, called ‘WAVE’, which will compare TTT to traditional surgery in 120 patients. The results are expected in 2027.  

Source: Queen Mary University of London

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Research Reveals New Insights into how LDL Cholesterol Works in the Body

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National Institute of Health (NIH) scientists have made a significant breakthrough in understanding how “bad” cholesterol, known as low-density lipoprotein-cholesterol or LDL-C, builds up in the body. The researchers were able to show for the first time how the main structural protein of LDL binds to its receptor – a process that starts the clearing of LDL from the blood – and what happens when that process gets impaired.

The findings, published in Nature, further the understanding of how LDL contributes to heart disease, the world’s leading cause of death, and could open the door to personalising LDL-lowering treatments like statins to make them even more effective.

“LDL is one of the main drivers of cardiovascular disease which kills one person every 33 seconds, so if you want to understand your enemy, you want to know what it looks like,” said Alan Remaley, MD, PhD, co-senior author on the study who runs the Lipoprotein Metabolism Laboratory at NIH’s National Heart, Lung, and Blood Institute.

Until now scientists have been unable to visualise the structure of LDL, specifically what happens when it links up with its receptor, a protein known as LDLR. Typically, when LDL binds to LDLR, the process of clearing LDL from the blood begins. But genetic mutations can prevent that work, causing LDL to build up in the blood and get deposited into the arteries as plaque, which can lead to atherosclerosis, a precursor for heart disease.

In the new study, the researchers were able to use high-end technology to get a view of what’s happening at a critical stage of that process and see LDL in a new light.

“LDL is enormous and varies in size, making it very complex,” explained Joseph Marcotrigiano, PhD, chief of the Structural Virology Section in the Laboratory of Infectious Diseases at NIH’s National Institute of Allergy and Infectious Diseases and co-senior author on the study. “No one’s ever gotten to the resolution we have. We could see so much detail and start to tease apart how it works in the body.”

Using cryo-electron microscopy, the researchers were able to see the entirety of the structural protein of LDL when it bound to LDLR. Then, with AI-driven protein prediction software, they were able to model the structure and locate the known genetic mutations that result in increased LDL.

The researchers found that many of the mutations that mapped to the location where LDL and LDLR connected, were associated with familial hypercholesterolaemia (FH). FH is marked by defects in how the body uptakes LDL into its cells, and people with it have extremely high levels of LDL and can have heart attacks at a very young age. They found that FH-associated variants tended to cluster in particular regions on LDL.

The study findings could open new avenues to develop targeted therapies aimed at correcting these kinds of dysfunctional interactions caused by mutations. But, as importantly, the researchers said, they could also help people who do not have genetic mutations, but who have high cholesterol and are on statins, which lower LDL by increasing LDLR in cells. By knowing precisely where and how LDLR binds to LDL, the researchers say they may now be able to target those connection points to design new drugs for lowering LDL from the blood.

Source: NIH/National Heart, Lung and Blood Institute

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Thrombolytic Drug Still Effective up to 24 Hours after Ischaemic Stroke Onset

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Credit: American Heart Association

The thrombolytic medication, alteplase, improved stroke patients’ recovery by more than 50% when given up to 24 hours after the beginning of an ischaemic stroke, according to preliminary late-breaking science presented at the American Stroke Association’s International Stroke Conference 2025.

These results give hope to stroke patients worldwide who may not be able to access thrombolytic medications within the approved time window, which in China is within 4.5 hours, said the trial’s principal investigator Min Lou, MD, PhD, a professor at the Second Affiliated Hospital of Zhejiang University’s School of Medicine in China.

In the US, alteplase is approved to treat stroke within three hours of symptom onset and is recommended for use up to 4.5 hours for select patients. Other research has indicated it may also work well in some patients 4.5 to 9 hours after stroke onset.

The American Heart Association/American Stroke Association 2019 Guidelines for the Early Management of Patients with Acute Ischemic Stroke note that IV alteplase within 4.5 hours of stroke onset is the standard of care for most ischaemic stroke patients in the United States.

Researchers enrolled 372 stroke patients whose symptoms began 4.5 hours to 24 hours earlier. They used widely available CT perfusion imaging (advanced brain scanning) to confirm that these patients still had brain tissue that could recover with treatment. Participants were randomised to receive alteplase, while the other received standard stroke care of antiplatelet therapy at the discretion of the investigator, based on the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2018. Functional recovery was assessed at 90 days.

“We believe these findings mean more people may return to normal or near-normal lives after a stroke, even if they receive treatment later than originally thought beneficial,” Lou said. “This method of treatment could become the new standard, especially in hospitals that use CT perfusion imaging. This technology helps health care professionals see how blood flows in different parts of the brain after an ischemic stroke. This could extend treatment eligibility to millions more patients across the globe.”

The study found:

  • 40% of participants treated with alteplase had little to no disability after 90 days, compared to 26% of those who received standard care – a 54% higher chance of functional recovery.
  • Less than 3% of participants in either group received rescue mechanical clot removal as an additional treatment.
  • Rates of death were the same (10.8%) for both groups.
  • The risk of brain bleeding was higher among those who received alteplase than among participants who did not (3.8% vs. 0.5%), but researchers believe this is a manageable risk.

“We also need to look more closely at how safe and effective other clot-dissolving medications, like tenecteplase, are when given after a stroke, especially beyond the usual time frames. It’s also important to learn if our findings apply to other groups of people, especially in areas with different stroke risks and health care resources,” Lou explained.

Study limitations include the that both participants and researcher knew which treatment was being given, which could have introduced bias, and results may not be generalizable to patients outside of China.

Study design, background and details:

  • The study enrolled 372 stroke patients in a multicenter, prospective, randomized trial at 26 stroke centers in China.
  • The patient’s average age was 72 years, and 43% were women.
  • The trial used widely available CT perfusion imaging software to gauge salvageable brain tissue, making the findings more applicable to real-world clinical settings.
  • Enrolled patients were assigned to the alteplase group or a standard medical treatment group.
  • The primary outcome was a score of 0 or 1 on the modified Rankin scale, which scores disability from 0 (no symptoms) to 6 (death) at 90 days.

Study co-authors, funding and disclosures are available in the abstract.

Source: American Heart Association

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Regular Flossing may Lower Risk of Ischaemic Stroke and Atrial Fibrillation

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Flossing your teeth at least once a week may be linked to a lower risk of stroke caused by blood clotting and atrial fibrillation, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2025. The meeting is in Los Angeles, Feb. 5-7, 2025, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

“A recent global health report revealed that oral diseases – such as untreated tooth decay and gum disease – affected 3.5 billion people in 2022, making them the most widespread health conditions,” said study lead author Souvik Sen, MD, MS, MPH, chair of the Department of Neurology, Prisma Health Richland Hospital and the University of South Carolina School of Medicine in Columbia, South Carolina. “We aimed to determine which oral hygiene behaviour – dental flossing, brushing or regular dentist visits – has the greatest impact on stroke prevention.”

The Atherosclerosis Risk in Communities (ARIC) study, one of the first large-scale investigations of this kind in the US, assessed the home use of dental floss through a structured questionnaire of more than 6000 people. Among those who reported flossing, 4092 had not experienced a stroke, and 4050 had not been diagnosed with atrial fibrillation (AFib).

Participants were asked about their status regarding high blood pressure, diabetes, high cholesterol, smoking, body mass index, education, regular brushing and dentist visits. During the 25 years of follow-up, 434 participants were identified as having strokes, of which 147 were larger artery brain clots, 97 were heart-driven clots and 95 were hardening of the smaller arteries. Additionally, 1291 participants were noted to have experienced AFib.

The analysis found:

  • Flossing was associated with a 22% lower risk of ischaemic stroke, 44% lower risk of cardioembolic stroke (blood clots traveling from the heart) and 12% lower risk of AFib.
  • The associated lower risk was independent of regular brushing and routine dental visits or other oral hygiene behaviours.
  • Increasing the frequency of flossing had a greater chance of stroke risk reduction.
  • Flossing was also associated with a lower chance of cavities and periodontal disease.

Researchers were surprised by the reduction of irregular heartbeats, or AFib. AFib is the most common form of irregular heartbeat. It can lead to stroke, heart failure or other cardiovascular complications.

“Oral health behaviours are linked to inflammation and artery hardening. Flossing may reduce stroke risk by lowering oral infections and inflammation and encouraging other healthy habits,” Sen said. “Many people have expressed that dental care is costly. Flossing is a healthy habit that is easy to adopt, affordable and accessible everywhere.”

Study limitations include that data were based on answers to a questionnaire, and the 25-year follow-up appears to have focused on stroke and heart outcomes only. There was no follow-up concerning flossing or other oral behaviours over the years, Sen said.

Source: American Heart Association

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Propranolol may Halve Risk of Ischaemic Stroke in Women with Migraines

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Credit: American Heart Association

Propranolol, a drug often used to treat hypertension and prevent migraines was associated with a reduction in ischaemic stroke risk among women – but not men – using the drug for migraine prevention, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2025. The meeting is in Los Angeles, Feb. 5-7, 2025, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

The beta blocker propranolol had a stronger protective effect for ischaemic stroke risk in women with migraine, particularly those without aura. The medication did not have the same protective effect on men.

Migraine headaches are common in the general population, but they occur three times more often in women than in men. This debilitating condition is associated with an increased risk of stroke. While the beta blocker propranolol can be used to prevent migraines, its effectiveness in reducing overall stroke risk is still uncertain.

“Migraine is an often-ignored risk factor for cardiovascular issues. Until recently, preventive treatments for people who have migraines were not available,” said lead study author Mulubrhan Mogos, PhD, MSc, FAHA, an assistant professor at Vanderbilt University School of Nursing. “Many women suffer from migraines, and it’s important to note that propranolol may be beneficial for these women, particularly those who experience migraine without aura. This is an important discovery for those dealing with migraines.”

Mogos also noted that migraine disproportionately affects women from historically under-resourced communities, and this disparity may impact the ability to achieve education goals or maintain stable employment, creating a vicious cycle. While new treatments have proven effective, they may not be accessible to women in these groups due to high costs.

For the study, researchers reviewed more than 3 million electronic health records from two large databases. In separate analyses, researchers identified people with migraine who developed stroke and a control group of those with migraine who did not develop stroke. They then assessed whether the individuals were treated with propranolol for migraine and whether that treatment had impacted stroke risk.

“We initially looked at overall stroke and then ischemic stroke specifically. We refined our analysis further by controlling for possible confounders and found the association is significant and stronger for ischaemic stroke,” Mogos said.

After adjusting for potential variables, such as demographics (age, sex, race), other conditions (high blood pressure, diabetes, etc) and hormonal factors (use of birth control, pregnancy – considered separately for each woman) that might affect results the analysis found:

  • Propranolol was significantly associated with a reduced risk of ischaemic stroke in women with migraine, particularly in those without aura. The risk of developing a stroke was 52% lower for women taking the medication in one database analysis and 39% lower in the other. No stroke risk reduction was seen in men in either analysis group.
  • The protective effect of propranolol was stronger for ischaemic stroke and in women with migraine without aura. Migraine aura can include disturbances, such as flashing lights, blind spots, zigzag patterns or seeing coloured spots. Other symptoms include tingling or numbness in the face or hands, difficulty speaking, dizziness or confusion.
  • Secondary analyses showed lower overall stroke rates in women taking propranolol at multiple time points in both databases.

“Our findings indicate that women and health care professionals should discuss the advantages of preventive migraine interventions. For under-resourced individuals who bear a greater burden from this condition and may lack access to new treatments, we must ensure these treatments are available to them. This approach can help reduce health disparities,” Mogos said.

The main limitation is that this was a review of past data using electronic health records, which may introduce biases, such as misclassification errors from reliance on ICD codes (codes used to classify and report health conditions and diseases). These findings highlight the need for studies that look forward in time to confirm these results.

Source: American Heart Association

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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