Not all acute myocardial infarction patients should be offered routine screening for the stomach ulcer bacterium Helicobacter pylori. However, it is possible that some patient groups with an elevated risk of post-infarction gastrointestinal bleeding benefit from such a test, concludes a large-scale study from Karolinska Institutet and Södersjukhuset published in the journal JAMA.
Upper gastrointestinal bleeding is a serious complication that affects approximately two per cent of patients within a year of a myocardial infarction.
“It’s associated with increased mortality and the risk of recurring cardiovascular events,” says the study’s lead author Robin Hofmann, senior consultant at the Department of Cardiology, Södersjukhuset, and associate professor at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet. “We therefore wanted to examine if screening for the common Helicobacter pylori bacterium, which causes gastritis and gastric ulcers, can reduce the risk of bleeding. This is currently not routine practice.”
The randomised study included almost 18 500 myocardial infarction patients at 35 hospitals in Sweden. Half the group was tested for the bacterium and treated with antibiotics and protein pump inhibitors by their doctors if testing positive, while the other half received routine care without an extra test or treatment.
Effective in anaemic patients
After almost two years’ follow-up, the researchers found that there were slightly fewer individuals in the screening programme who had suffered gastrointestinal bleeding, but not enough to make the difference statistically significant. However, they found a positive effect of the screening when studying specific sub-groups of patients, such as those with anaemia or kidney failure. A particularly positive effect was observed in patients with moderate to severe anaemia, who suffered gastrointestinal bleeding at roughly half the rate if they underwent screening.
“Our results suggest that screening for Helicobacter pylori does not need to be done routinely for all individuals following a heart attack,” says Dr Hofmann. “On the other hand, testing and treatment could be a meaningful complement for selected patient groups with an elevated risk of bleeding.”
The researchers will now go on to study the long-term effects and try to identify which groups will benefit most from screening.
Early withdrawal of aspirin following successful percutaneous coronary intervention (PCI) for acute coronary syndrome and in low-risk patients following an acute myocardial infarction (MI) was the focus of two separate hot line trials presented at ESC Congress 2025. A third trial provided insights into early escalation and late de-escalation of antiplatelet therapy after complex PCI.
In the NEO-MINDSET trial, simultaneously published in NEJM, researchers in Brazil randomised approximately 3400 patients within the first four days of hospitalisation following a successful PCI to either stop treatment with aspirin and receive potent P2Y12 inhibitor monotherapy (ticagrelor or prasugrel) or to receive dual antiplatelet therapy (DAPT) that included aspirin and a potent P2Y12 inhibitor for 12 months.
At 12 months, the primary endpoint of death from any cause, MI, stroke or urgent revascularisation had occurred in 119 patients in the monotherapy group and in 93 patients in the DAPT group (p = 0.11 for noninferiority). Researchers also noted that major or clinically relevant nonmajor bleeding occurred in 33 patients assigned to monotherapy vs 82 patients assigned to DAPT. Stent thrombosis occurred in 12 patients in the monotherapy group and in 4 in the dual antiplatelet therapy group.
“We failed to demonstrate the noninferiority of aspirin-free monotherapy initiated immediately after PCI with regard to the ischaemic primary endpoint over 12 months,” said Principal Investigator Pedro Lemos, MD. “Results from the landmark analysis suggest that the excess ischaemic risk with monotherapy occurred in the first 30 days, with comparable outcomes thereafter. Bleeding appeared to be lower at both 30 days and 12 months with monotherapy versus DAPT.”
In TARGET-FIRST, also simultaneously published inNEJM, P2Y12-inhibitor monotherapy was noninferior to continued DAPT with respect to the occurrence of adverse cardiovascular and cerebrovascular events among low-risk patients with acute MI who had undergone early complete revascularisation and had completed one month of DAPT without complications. It also resulted in lower incidence of bleeding events.
Nearly 2000 patients from 40 centres in Europe were randomised to receive P2Y12-inhibitor monotherapy or to continue DAPT for 11 months. A primary-outcome event occurred in 20 patients (2.1%) in the P2Y12-inhibitor monotherapy group and in 21 patients (2.2%) in the dual antiplatelet therapy group (p = 0.02 for noninferiority). Major bleeding occurred in 2.6% of the patients assigned to P2Y12-inhibitor monotherapy group compared with 5.6% of those assigned to DAPT (p = 0.002 for superiority). The incidence of stent thrombosis and serious adverse events appeared to be similar in the two groups, researchers said.
Principal Investigator Giuseppe Tarantini, MD, noted that no previous randomised trials have assessed early aspirin discontinuation in acute MI patients who achieve early, complete revascularisation with modern stents. “These results reflect the benefits of modern stents, high procedural success and optimal medical therapy, making early aspirin discontinuation feasible in this selected population,” he said.
The TAILORED-CHIP trial found early escalation and late de-escalation of antiplatelet therapy is not beneficial in patients with high-risk anatomical or clinical characteristics undergoing complex PCI.
Researchers in South Korea randomised approximately 2000 patients to standard DAPT (clopidogrel plus aspirin for 12 months) or a tailored antiplatelet strategy consisting of early escalation (low-dose ticagrelor at 60mg twice daily plus aspirin for 6 months) followed by late de-escalation (clopidogrel monotherapy for 6 months).
Overall findings showed no significant difference in the incidence of major ischemic events at 12 months with tailored therapy compared with standard DAPT. However, the incidence of clinically relevant bleeding was significantly higher with tailored therapy, according to study investigators.
“Our results suggest that a tailored strategy in patients undergoing complex high-risk PCI does not provide a net clinical benefit,” said Principal Investigator Duk-Woo Park, MD, PhD, FACC. “We observed an increase in bleeding complications without a significant reduction in ischaemic events. This challenges the notion that ‘more is better’ even in carefully selected patients at high ischaemic risk.”
Beta-blocker therapy showed no evidence of an effect on all-cause death, reinfarction or heart failure admission in patients with myocardial infarction (MI) managed invasively who had left ventricular ejection fraction (LVEF) ≥ 40%, according to late-breaking research from the REBOOT trial presented in a Hot Line session today at ESC Congress 20251 and simultaneously published in the New England Journal of Medicine.
Explaining the rationale for the REBOOT trial, Principal Investigator, Professor Borja Ibáñez from the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Fundación Jiménez Díaz University Hospital, Madrid, Spain, said: “Beta-blockers have long been a foundational treatment after acute MI; however, supporting evidence is derived from trials that predate modern standards of care − before the time of routine reperfusion, invasive management, potent antiplatelet therapies and statins. Re-examining the role of beta-blockers is warranted, particularly among patients with uncomplicated MI and LVEF > 40% in whom the benefits of beta-blockers are not well established, unlike with reduced LVEF (≤ 40%).”
The investigator-initiated randomised open blinded-endpoint REBOOT trial was conducted at 109 centres across Spain and Italy. Patients with MI (with or without ST-segment elevation) were eligible for enrolment if they underwent invasive management during the index hospitalisation and had a predischarge LVEF > 40%, with no history or signs of heart failure. Patients were randomised 1:1 to beta-blocker or no beta-blocker therapy. The primary endpoint was a composite of all-cause mortality, nonfatal reinfarction or heart failure admission.
Among 8505 patients who underwent randomisation, the mean age was 61 years and 19.3% were women. A total of 10% had a prior MI and 12% were on beta-blocker treatment before the index hospitalisation.
After a median follow-up of 3.7 years, the primary composite outcome of all-cause death, nonfatal reinfarction or heart failure admission occurred in a similar proportion of patients in each group: 22.5/1000 patient-years in beta-blocker group and 21.7/1000 patient-years in the no beta-blocker group (hazard ratio [HR] 1.04; 95% confidence interval [CI] 0.89 to 1.22; p=0.63).
All-cause mortality occurred in 11.2 and 10.5/1000 patient-years on beta-blocker therapy and no-beta blocker therapy, respectively (HR 1.06; 95% CI 0.85 to 1.33). Nonfatal reinfarction occurred in 10.2 and 10.1/1000 patient-years, respectively (HR 1.01; 95% CI 0.80 to 1.27), while heart failure admission occurred in 2.7 and 3.0/1,000 patient-years, respectively (HR 0.89; 95% CI 0.58 to 1.38).
Regarding safety, admission for stroke occurred in 2.6/1000 patient-years in the beta-blocker group and 1.7/1000 patient-years in the no beta-blocker group (HR 1.50; 95% CI 0.90 to 2.49). Admission for symptomatic advanced atrioventricular block occurred in 0.5 of patients in the beta-blocker group and 0.4/1000 patient-years of patients in the no beta-blocker group (HR 1.18; 95% CI 0.40 to 3.50).
There appeared to be an absence of benefit with beta-blockers across the prespecified subgroups. However, fewer events were noted in patients with mildly reduced LVEF (40−49%) on beta-blockers vs no beta-blockers, although low patient numbers limit interpretability. Women experienced overall more events, especially when on beta-blockers.
Professor Ibáñez concluded: “Beta-blocker therapy showed no evidence of benefit across the study population of patients with MI managed invasively who had LVEF > 40%. However, as also presented today at ESC Congress, a meta-analysis of data from four trials, including REBOOT, suggest there may be a positive signal in patients with mildly reduced LVEF (40−49%).2”
Many survivors of cardiogenic shock showed evidence of new cognitive impairment after leaving the hospital, according to a study led by UT Southwestern Medical Center researchers. The findings, published in the Journal of the American College of Cardiology, highlight a need to screen survivors and provide referrals to neuropsychology experts, the authors said.
“Our study demonstrated that nearly two-thirds of cardiogenic shock survivors experienced cognitive impairment within three months of hospital discharge, underscoring a critical but overlooked aspect of recovery,” said senior investigator James de Lemos, MD, Professor of Internal Medicine and Chief of the Division of Cardiology at UT Southwestern. “The findings are important for developing interventions that focus not only on improving survival but also on preventing or mitigating the functional consequences of cardiogenic shock, including cognitive decline.”
Cardiogenic shock results from heart failure, heart attack, or complications following cardiac surgery, and is characterised by a sudden drop in heart pumping ability. It results in acute hypoperfusion and hypoxia of the organs and has historically resulted in high mortality.
With advances in treatment during the past two decades, up to 70% of patients suffering from cardiogenic shock can now survive. But there is limited understanding of survivors’ recovery and quality of life after they leave the hospital.
“Our study is the first to systematically examine the cognitive outcomes of cardiogenic shock survivors, evaluating how cognition impacts patients’ ability to return to daily activities,” said Eric Hall, M.D., a clinical fellow in the Division of Cardiology who was the study leader and first author. “We found that cardiogenic shock is associated with cognitive impairment, which is an under-recognized consequence strongly linked to patients’ overall quality of life.”
UTSW researchers conducted the study by enrolling 141 patients who had survived cardiogenic shock before being discharged. To establish a baseline, family members completed a questionnaire, the AD8 survey, about the patients’ cognitive function before hospitalisation.
Before discharge, each patient completed the Montreal Cognitive Assessment-Blind (bMoCA) to screen for signs of cognitive impairment. Three months after discharge, patients repeated the assessments, allowing researchers to track changes in thinking ability and daily functioning over time.
Among patients with no sign of cognitive impairment before admission, 65% were found to have new impairment at discharge, and 53% continued to show impairment at their three-month follow-up. UTSW researchers emphasized that these findings should inform the development of comprehensive survivorship programs including screening protocols to identify impairments patients face and rehabilitation programs to help them recover from those challenges.
“We hope to use this study as a foundation to develop targeted rehabilitation strategies that connect patients with neuropsychology experts and improve long-term recovery in cardiogenic shock survivors,” Dr de Lemos said.
Despite clinicians recommending that many patients with diabetes take statins, nearly one in five opt to delay treatment. In a new study, researchers from Mass General Brigham found that patients who started statin therapy right away reduced the rate of heart attack and stroke by one third compared to those who chose to delay taking the medication. The results, which can help guide decision-making conversations between clinicians and their patients, are published in the Journal of the American Heart Association.
“I see patients with diabetes on a regular basis, and I recommend statin therapy to everyone who is eligible,” said senior author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “Some people refuse because they want to first try lifestyle interventions or other drugs. But other interventions are not as effective at lowering cholesterol as starting statin therapy as soon as possible. Time is of the essence for your heart and brain health.”
Heart attacks and strokes remain the leading cause of complications and mortality for patients with diabetes. Statin therapy reduces risk of these cardiovascular events by preventing plaque buildup in the blood vessels.
The researchers used an artificial intelligence method called Natural Language Processing to gather data from the electronic health records of 7239 patients at Mass General Brigham who ultimately started statin therapy during the nearly 20-year study period. The median patient age was 55, with 51% being women, 57% white, and a median HbA1c of 6.9.
Nearly one-fifth (17.7%) of the patients in the study declined statin therapy when it was first recommended by their clinicians, then later accepted the therapy (after a median of 1.5 years) upon repeated recommendation by their clinician. Of those who delayed, 8.5% had a heart attack or stroke. But for patients who started statins immediately, the rate of those cardiovascular events was just 6.4%.
“Clinicians should recognize the increased cardiovascular risk associated with delaying statin therapy for patients with diabetes and use this information to guide shared decision-making conversations with their patients,” said Turchin.
Researchers have developed a new therapy that can be injected intravenously right after a heart attack to promote healing and prevent heart failure. The therapy both prompts the immune system to encourage tissue repair and promotes survival of heart muscle cells after a heart attack. Researchers tested the therapy in rats and showed that it is effective up to five weeks after injection.
The research team, led by bioengineers at the University of California San Diego and chemists at Northwestern University, published their findings in Advanced Materials.
“Preventing heart failure after a heart attack is still a major unmet clinical need,” said Karen Christman, one of the study’s corresponding authors and a professor of bioengineering at UC San Diego. “The goal of this therapy is to intervene very soon after someone suffers a heart attack to keep them from ultimately going into heart failure.”
Side by side comparison of heart muscle cells with and without treatment. Damage to the cells is shown in blue. On the left, tissue has been injected with saline and the damaged area is considerably larger. On the right, the issue was treated with the PLP platform and the damaged area is significantly smaller.
The therapy could have broader applications, said Nathan Gianneschi, the paper’s other corresponding author and a professor in the Department of Chemistry at Northwestern.
“This therapeutic platform has tremendous potential for several diseases, including everything from macular degeneration to multiple sclerosis and kidney disease,” Gianneschi said.
The platform aims to block the interaction of two key proteins that intervene in the body’s response to stress and inflammation. When the protein Nrf2 is activated, cells resist the degradation brought on by inflammation. But KEAP1 binds with Nrf2 to degrade it in turn. After a heart attack, this process of degradation has to be stopped so that tissues can health better.
The protein-like polymer, or PLP, platform is made from a polymer that mimics Nrf2. Once injected intravenously, it finds KEAP1 and binds to it, preventing it from binding to the actual Nrf2 protein and degrading it.
Researchers injected rat models after a heart attack with either the PLP platform or a saline solution. The team was blinded to which animals received the polymer or saline. After five weeks, the rodents underwent MRIs while sedated. The animals injected with the polymer showed better cardiac function and significantly more healing in their heart muscle tissue. Other tests also showed that genes that promote healing of tissues were expressed more.
Researchers describe the study as a proof of concept. Before moving on to tests in larger mammals, they want to optimize the design and dosage, and conduct further analysis.
“Proteins are the molecular machines that drive all essential cellular function, and dysregulated intracellular protein-protein interactions are the cause of many human diseases,” Gianneschi said. “Existing drug modalities are either unable to penetrate cells or cannot effectively engage these large disease target domains. We are looking at these challenges through a new lens.”
The therapy method was developed by Gianneschi, while he was a faculty member at UC San Diego, where he is now an adjunct faculty. He continued working on the technology at Northwestern.
Photo by Mikhail Nilov: https://www.pexels.com/photo/paramedics-using-a-defibrillator-on-a-patient-8942635/
Patients who receive an add-on medication soon after a heart attack have a significantly better prognosis than those who receive it later, or not at all. These are the findings of a new study from researchers at Lund University in Sweden and Imperial College London.
Their analysis suggests that treating patients earlier with a combination of statins and the cholesterol-lowering drug ezetimibe could prevent thousands of new heart attacks in the UK over a decade.
Cardiovascular disease is by far the most common cause of death worldwide, with heart attack (‘myocardial infarction’) being the most common acute event.
For those who survive a heart attack, the risk of a new heart attack is greatest in the first year after the initial event because the blood vessels are more sensitive, making it easier for blood clots to develop.
Our findings suggest that a simple change in treatment guidelines could have a huge impact on patients and reduce the demand on the NHS.
Professor Kausik Ray, School of Public Health
Reducing LDL or “bad” cholesterol in the blood can stabilise changes in the vessels, decreasing the risk for new events.
The current treatment guidelines for patients are high-potency statins immediately after a heart attack, to lower their cholesterol levels.
However, the majority of patients do not reach recommended cholesterol levels using only statins, and so need an add-on treatment, such as ezetimibe.
“Today’s guidelines recommend stepwise addition of lipid-lowering treatment. But it’s often the case that this escalation takes too long, it’s ineffective and patients are lost to follow-up,” says Margrét Leósdóttir, Associate Professor at Lund University and senior cardiology consultant at Skåne University Hospital in Malmö, Sweden. “By giving patients a combination treatment earlier, we could help to prevent many more heart attacks.”
Co-investigator Professor Kausik Ray, from Imperial College London’s School of Public Health, said: “This study shows that we could save lives and reduce further heart attacks by giving patients a combination of two low-cost drugs.
“But at the moment patients across the world aren’t receiving these drugs together. That’s causing unnecessary and avoidable heart attacks and deaths – and also places unnecessary costs on healthcare systems.
“Our study shows the way forward; care pathways must now change for patients after this type of heart event.”
Reducing heart attacks
In the latest study, the international team examined outcomes for heart attack patients if they received a combination of statins with the add-on therapy ezetimibe (within 12 weeks after a heart attack), statins with ezetimibe added later (between 13 weeks and 16 months), or just statins with no ezetimibe at all.
Based on Swedish registry data from 36 000 patients who had a heart attack between 2015 and 2022, the researchers used advanced statistical models to emulate a clinical trial.
The results show that patients who received a combination treatment of statins and ezetimibe within 12 weeks of a heart attack and were able to lower cholesterol to the target level early, had a better prognosis and less risk of new cardiovascular events and death than those who received the add-on treatment later, or not at all.
From the analysis, the researchers believe many new heart attacks, strokes and deaths could be prevented every year internationally if the treatment strategy were to be changed.
Under a scenario in which 100% of patients would receive ezetimibe early, they estimate 133 heart attacks could be avoided in a population of 10 000 patients in 3 years.
The researchers suggest that in the UK, which records an estimated 100 000 hospital admissions from heart attacks a year,[1] this would equate to an estimated 5000 heart attacks being prevented over a ten year period.[2]
Improving guidance
Dr Leósdóttir said: “Combination therapy is not applied up-front for two main reasons. General recommendations are not included in today’s guidelines and a precautionary principle is applied to avoid side effects and overmedication.
However, there are positive effects from applying both medicines as soon after the infarction as possible. Not doing this entails an increased risk. In addition, the drug we have examined in the study causes few side effects and is readily available and inexpensive in many countries.”
Margrét Leósdóttir hopes that the research results will in time provide support for changes in the recommendations. A treatment algorithm has already been introduced at her hospital in Sweden to help doctors to prescribe appropriate lipid-lowering treatment for patients who have had a myocardial infarction.
It has been noted that patients achieve their treatment goals earlier and two months after the infarction twice as many patients have reduced their bad cholesterol to the target level, compared with previously.
“Several other hospitals in Sweden have also adopted the algorithm and there are similar examples from other countries that have produced as good results. My hope is that even more will review their procedures, so that more patients will get the right treatment in time, and we can thereby prevent unnecessary suffering and save lives.”
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.”
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.”
There is no difference in the effectiveness of the two most commonly used methods for administering medication during out-of-hospital cardiac arrest, according to a large new clinical study published in NEJM.
This is shown in a large new clinical study from Aarhus University and Prehospital Services, Region Midtjylland, which compared two ways of accessing the bloodstream: a standard needle in a vein (venous catheter) and a so-called intraosseous needle, which is inserted into the bone marrow.
“When a person suffers cardiac arrest outside the hospital, it is crucial to quickly access the bloodstream to administer life-saving medication. We investigated which method is best,” explains Lars Wiuff Andersen, professor and physician at the Department of Clinical Medicine, Aarhus University, Prehospital Services, Region Midtjylland, and Aarhus University Hospital.
Venous catheter or intraosseous needle?
Until now, healthcare professionals have preferred using a venous catheter, but it can be difficult to place as veins may collapse during cardiac arrest.
The intraosseous needle, inserted either into the shinbone or upper arm, can be faster and easier to use in an emergency.
Therefore, it’s interesting to investigate the effectiveness of both methods, explains Lars Wiuff Andersen.
The study, based on data from nearly 1500 cardiac arrest patients across Denmark, showed that about 30 percent of patients in both groups had their blood circulation restored.
“The two methods proved to be equally effective in restoring blood circulation and saving lives. There was no difference in the patients’ survival or quality of life,” explains Mikael Fink Vallentin, associate professor at the Department of Clinical Medicine and Prehospital Services, Region Midtjylland, and co-lead author of the study.
May change guidelines
According to the researchers behind the study, the results may impact future guidelines, which previously recommended venous catheters as the first choice.
However, Lars Wiuff Andersen notes that it is too early to say exactly how the guidelines will change.
“Our data must be considered alongside a large clinical trial from the UK, which is being published simultaneously with our study. Combined, these two trials will likely influence guidelines for cardiac arrest treatment, but a thorough review of the results will be needed,” he says.
More unanswered questions
There are still several unanswered questions, especially regarding whether specific groups of cardiac arrest patients benefit more from one method than the other.
The researchers are continuing to analyse and compare their own data with data from the UK trial.
The Danish research team has already planned a new, large clinical trial to investigate which method is best for delivering electric shocks during cardiac arrest.
“We hope to gain even more answers on how to best save lives in cardiac arrest in the future,” says Lars Wiuff Andersen.
