Culture

Indigenous peoples in Canada have higher rates of death and complications after surgery and lower rates of surgeries than other populations, found new research published in CMAJ (Canadian Medical Association Journal).

"Understanding surgical outcomes and access to surgical services is a vital step toward addressing colonialism and structural racism within health care, so we can identify the gaps and determine what needs to be improved," said Dr. Nadine Caron, a general surgeon in Prince George and co-director of the Centre for Excellence in Indigenous Health at the University of British Columbia.

Access to safe and timely surgery is essential, as surgery is responsible for 65% of cancer cure and control, can prevent death following trauma and, in the case of cesarean births, reduces newborn deaths by up to 70%.

Researchers looked at 28 studies that compared surgical outcomes across a range of procedures in Indigenous Peoples to outcomes in non-Indigenous peoples in Canada. Combined, the studies included 1.9 million patients, of whom 10.2% (202,056) identified as Indigenous, although few specifically addressed Inuit or Métis populations.

The research team found Indigenous Peoples had higher rates of complications after surgery; were less likely to undergo life-saving surgery, including cardiac surgery and cesarean deliveries; and experienced longer wait times for kidney transplants. Four studies indicated that Indigenous Peoples had a 30% increased risk of death after surgery and were less likely to undergo surgeries such as joint replacements that improve quality of life.

These findings are consistent with those for Indigenous Peoples in other high-income countries. As the Canadian data were limited and of poor quality, the research team calls for more research and consistent data collection methods.

"This study tells Canadians two things. We need better data, and the data we have tell us that we need to do better," said Dr. Jason McVicar, a Métis anesthesiologist at The Ottawa Hospital, assistant professor at the University of Ottawa and the lead author of the study. He added, "Better-quality research by Indigenous investigators and real-time outcome monitoring for Indigenous patients are essential to eliminating structural racism in the health care system."

The research team has concerns about the effect of the COVID-19 pandemic on access to surgery for Indigenous Peoples. "The pandemic has exposed societal disparities and disproportionately affected vulnerable populations," says Dr. Donna May Kimmaliardjuk, a cardiac surgeon and fellow at The Cleveland Clinic. "This research illuminates the inequities built into our surgical systems. When we begin to address the backlog, those with the political agency to strongly advocate for themselves will inevitably get to the front of the line, which will again disproportionately impact First Nations, Inuit and Métis communities."

Whether it's plankton exposed to parasites or people exposed to pathogens, a host's initial immune response plays an integral role in determining whether infection occurs and to what degree it spreads within a population, new University of Colorado Boulder research suggests.

The findings, published May 13 in The American Naturalist, provide valuable insight for understanding and preventing the transmission of disease within and between animal species. From parasitic flatworms transmitted by snails into humans in developing nations, to zoonotic spillover events from mammals and insects to humans--which have caused global pandemics like COVID-19 and West Nile virus--an infected creature's immune response is a vital variable to consider in calculating what happens next.

"One of the biggest patterns that we're seeing in disease ecology and epidemiology is the fact that not all hosts are equal," said Tara Stewart Merrill, lead author of the paper and a postdoctoral fellow in ecology. "In infectious disease research, we want to build host immunity into our understanding of how disease spreads."

Invertebrates are common vectors for disease, which means they can transmit infectious pathogens between humans or from animals to humans. Vector-borne diseases, like malaria, account for almost 20% of all infectious diseases worldwide and are responsible for more than 700,000 deaths each year.

Yet epidemiological studies have rarely considered invertebrate immunity and recovery in creatures that are vectors for human disease. They assume that once exposed to a pathogen, the invertebrate host will become infected.

But what if it was possible for invertebrates to fight off these diseases, and break the link in the chain that passes them on to humans?

While observing a tiny species of zooplankton (Daphnia dentifera) throughout its lifecycle and exposure to a fungal parasite (Metschnikowia bicuspidata), the researchers saw this potential in action. Some of the plankton were good at stopping fungal spores from entering their bodies, and others cleared the infection within a limited window of time after ingesting the spores.

"Our results show that there are several defenses that invertebrates can use to reduce the likelihood of infection, and that we really need to understand those immune defenses to understand infection patterns," said Stewart Merrill.

Unexpected recovery

Stewart Merrill started this work in her first year as a doctoral student at the University of Illinois, studying this little plankton and its collection of defenses. It's a gruesome process if the plankton fails to ward off the parasite: Its fungal spores attack the plankton's gut, fill its body and grow until they are released when the host finally dies.

But she noticed something that had not been recorded before: Some of the doomed plankton recovered. Several years later, she has found that when faced with identical levels of exposure, the success or failure of these infections depends on the strength of the host's internal defenses during this early limited window of opportunity.

Based on their observations of these individual outcomes, the researchers developed a simple probabilistic model for measuring host immunity that can be applied across wildlife systems, with important applications for diseases transmitted to humans by invertebrates.

"When immune responses are good, they act as a filter that reduces transmission," said Stewart Merrill. "But any environmental change that degrades immunity can actually amplify transmission, because it will let all of that exposure go through and ultimately become infectious."

It's a model that can also apply to COVID-19, as research from CU Boulder has shown that not all hosts are the same in transmitting the coronavirus, and exposure does not directly determine infection.

COVID-19 is also believed to be the result of a zoonotic spillover, an infection that moved from animals into people, and similar probabilistic models could be advantageous in predicting the occurrence and spread of future spillover events, said Stewart Merrill.

Understanding prevention of infection

Stewart Merrill hopes that a better understanding of infections in a simple animal like plankton can be applied more broadly to invertebrates that matter for human health.

In Africa, Southeast Asia, as well as South and Central America, 200 million people suffer from infections caused by schistosomes--invertebrates more commonly known as parasitic flatworms. They cause illness and death, and significant economic and public health consequences, so much so that the World Health Organization considers them the second-most socioeconomically devastating parasitic disease after malaria.

They're just one of many neglected tropical diseases transmitted to people by invertebrate hosts such as snails, mosquitoes and biting flies. These diseases infect a large portion of a population but occur in areas with low levels of sanitation that don't have the economic resources to address those diseases, said Stewart Merrill.

Schistosomes live in freshwater environments that people use for their drinking water, laundry and bathing. So even though there are treatments, the next day a person can easily get reinfected just by accessing the water they need. By better understanding how the flatworms themselves succumb to or fight off infection, scientists like Stewart Merrill help us get closer to stopping the chain of transmission into humans.

"We really need to work on understanding prevention of infection, and what that risk is in those aquatic systems, rather than just cures for infection," she said.

The good news is we can learn from the same invertebrates which infect us. In invertebrate hosts that suffer or die from their infections, there is a good incentive to learn how to build an immune response and fight it off. Some snails have even shown the ability to retain an immunological memory: If they get infected once and survive, then they might never get infected again.

"If we can better understand how the environment shapes those defenses, we could predict into the future how environmental changes might amplify or suppress risk of transmission to people," said Stewart Merrill.

A team including Northwestern University astrophysicists has developed the most realistic, highest-resolution 3D simulation of star formation to date. The result is a visually stunning, mathematically-driven marvel that allows viewers to float around a colorful gas cloud in 3D space while watching twinkling stars emerge.

Called STARFORGE (Star Formation in Gaseous Environments), the computational framework is the first to simulate an entire gas cloud -- 100 times more massive than previously possible and full of vibrant colors -- where stars are born.

It also is the first simulation to simultaneously model star formation, evolution and dynamics while accounting for stellar feedback, including jets, radiation, wind and nearby supernovae activity. While other simulations have incorporated individual types of stellar feedback, STARFORGE puts them altogether to simulate how these various processes interact to affect star formation.

Using this beautiful virtual laboratory, the researchers aim to explore longstanding questions, including why star formation is slow and inefficient, what determines a star's mass and why stars tend to form in clusters.

The researchers have already used STARFORGE to discover that protostellar jets -- high-speed streams of gas that accompany star formation -- play a vital role in determining a star's mass. By calculating a star's exact mass, researchers can then determine its brightness and internal mechanisms as well as make better predictions about its death.

Newly accepted by the Monthly Notices of the Royal Astronomical Society, an advanced copy of the manuscript, detailing the research behind the new model, appeared online today. An accompanying paper, describing how jets influence star formation, was published in the same journal in February 2021.

"People have been simulating star formation for a couple decades now, but STARFORGE is a quantum leap in technology," said Northwestern's Michael Grudi?, who co-led the work. "Other models have only been able to simulate a tiny patch of the cloud where stars form -- not the entire cloud in high resolution. Without seeing the big picture, we miss a lot of factors that might influence the star's outcome."

"How stars form is very much a central question in astrophysics," said Northwestern's Claude-André Faucher-Giguère, a senior author on the study. "It's been a very challenging question to explore because of the range of physical processes involved. This new simulation will help us directly address fundamental questions we could not definitively answer before."

Grudi? is a postdoctoral fellow at Northwestern's Center for Interdisciplinary Exploration and Research in Astrophysics (CIERA). Faucher-Giguère is an associate professor of physics and astronomy at Northwestern's Weinberg College of Arts and Sciences and member of CIERA. Grudi? co-led the work with Dávid Guszejnov, a postdoctoral fellow at the University of Texas at Austin.

From start to finish, star formation takes tens of millions of years. So even as astronomers observe the night sky to catch a glimpse of the process, they can only view a brief snapshot.

"When we observe stars forming in any given region, all we see are star formation sites frozen in time," Grudi? said. "Stars also form in clouds of dust, so they are mostly hidden."

For astrophysicists to view the full, dynamic process of star formation, they must rely on simulations. To develop STARFORGE, the team incorporated computational code for multiple phenomena in physics, including gas dynamics, magnetic fields, gravity, heating and cooling and stellar feedback processes. Sometimes taking a full three months to run one simulation, the model requires one of the largest supercomputers in the world, a facility supported by the National Science Foundation and operated by the Texas Advanced Computing Center.

The resulting simulation shows a mass of gas -- tens to millions of times the mass of the sun -- floating in the galaxy. As the gas cloud evolves, it forms structures that collapse and break into pieces, which eventually form individual stars. Once the stars form, they launch jets of gas outward from both poles, piercing through the surrounding cloud. The process ends when there is no gas left to form anymore stars.

Already, STARFORGE has helped the team discover a crucial new insight into star formation. When the researchers ran the simulation without accounting for jets, the stars ended up much too large -- 10 times the mass of the sun. After adding jets to the simulation, the stars' masses became much more realistic -- less than half the mass of the sun.

"Jets disrupt the inflow of gas toward the star," Grudi? said. "They essentially blow away gas that would have ended up in the star and increased its mass. People have suspected this might be happening, but, by simulating the entire system, we have a robust understanding of how it works."

Beyond understanding more about stars, Grudi? and Faucher-Giguère believe STARFORGE can help us learn more about the universe and even ourselves.

"Understanding galaxy formation hinges on assumptions about star formation," Grudi? said. "If we can understand star formation, then we can understand galaxy formation. And by understanding galaxy formation, we can understand more about what the universe is made of. Understanding where we come from and how we're situated in the universe ultimately hinges on understanding the origins of stars."

"Knowing the mass of a star tells us its brightness as well as what kinds of nuclear reactions are happening inside it," Faucher-Giguère said. "With that, we can learn more about the elements that are synthesized in stars, like carbon and oxygen -- elements that we are also made of."

The challenges that many women face in today's labour market are well documented, from lower employment rates than men to lower rates of pay. Previous studies have considered how the burden of family care, which often falls largely on women's shoulders, has contributed to this imbalance. However, few of these studies have considered why women are the ones to bear that care burden.
A new study, published in the KeAi journal China Economic Quarterly International, has used data from China to investigate the impact of the concept of gender roles on women's employment and earnings.

Study author, Chuanchuan Zhang, of China's Zhejiang University, explains: "Traditionally, studies on women's labour supply behaviour and labour market outcomes have mainly focused on economic, institutional and policy constraints. They have paid little attention to individual preferences or social beliefs.

"In recent years, with more and more interdisciplinary studies drawing on economics, psychology and sociology, researchers are looking at this topic from the perspectives of psychology, individual preferences and social concepts.

"For our study, we looked at the role of the community's concept of gender roles. And we found that the more traditional that perception, the less likely women are to be employed. For those who are employed, their total personal income and labour earnings are likely to be lower than men's."

Zhang, and his co-author Jingwen Wang, of China's Tsinghua University, began by collecting data on the numbers of March 8th Red Banner Pacesetters awarded locally in China in 1960 and 1979. These are honours that recognize outstanding women in China. They then used the awards as a proxy measure of the impact of women's liberation movements, and discovered that, over the course of those 19 years, the movements had significantly weakened traditional attitudes towards gender roles.

Wang explains: "This study shows that gender roles in Chinese culture, such as the traditional idea of "the husband is the breadwinner, the wife the housekeeper", are an important factor affecting Chinese women's labour market outcomes.

"However, although the traditional gender norm is deeply rooted, it is still significantly affected by economic and social changes such as women's liberation movements. To fundamentally correct employment and earnings inequality in China, it is necessary to gradually change traditional gender norms through cultural publicity and education, so we can create a cultural institutional environment that supports women's development."

The coronavirus pandemic has upended nearly every aspect of everyday life and continues to have devastating effects worldwide. It has also taken a significant toll on cardiovascular clinicians, many of whom provide direct care to patients with COVID-19, according to results of a new survey presented at the American College of Cardiology's 70th Annual Scientific Session.

Among those surveyed, burnout increased from 20% to 38% during the peak of the pandemic. Rates of burnout pre- and peak COVID-19 increased across all members of the cardiology team and was particularly striking among cardiovascular team members, which researchers said may be because they were more likely at the bedside as patients were dying. Among all cardiovascular clinicians--cardiologists, physician assistants, nurse practitioners, nurses, pharmacists and imaging technologists--half provided direct care to patients with COVID-19, and yet 1 out of 5 reported not having adequate personal protective equipment (PPE). Not surprisingly, the rate of burnout was higher in this group.

"We know from previous studies that burnout is pervasive in cardiology and medicine in general, but we felt it was important to take the temperature of our colleagues amid the COVID-19 pandemic. The prevalence of burnout among cardiovascular professionals nearly doubled when comparing pre- to peak COVID-19 levels," said Laxmi Mehta, MD, vice chair of wellness for the Department of Internal Medicine at the Ohio State University Wexner Medical Center and the study's lead author. "It clearly shows that there are lots of opportunities to improve the work environment; COVID-19 has really put a magnifying glass on the fact that things were bad and now have significantly worsened."

The survey revealed that some cardiovascular clinicians are thinking about leaving their jobs, in some cases, because of COVID-19. Plans to reduce clinical work hours in the next year, leave their current practice or retire early were reported by 23%, 13% and 13% of respondents, respectively, and notably higher among those who reported feeling burnt out. For some, COVID-19 is the key influencer for these decisions, with 17% of clinicians planning to reduce their clinical work hours, 12% planning to leave their current practice and 11% planning to retire due to COVID-19. The survey also revealed financial stressors exacerbated by COVID-19, with 41% of respondents reporting that their salary had been reduced to some degree. Roughly the same percentage of clinicians also reported inadequate health system support during the pandemic related to workers' basic needs, such as food, lodging, transportation, childcare and emotional support.

"Health systems need to take steps to help ensure basic safety, financial and personal needs of cardiology clinicians especially in the wake of COVID-19," Mehta said. "There are also still many unknowns with emerging variants and as our communities open more, some people are choosing not to get vaccinated, not to mention on top of the already taxed health systems, there are additional burdens of caring for patients with cardiovascular disease who delayed care and are now sicker than they would have been if they presented earlier."

The mini-Z survey on burnout was sent via email in November 2020 to 10,019 cardiologists, fellows-in-training and cardiovascular team members. A total of 1,288 people responded to the survey (456 U.S. and 436 international cardiologists, 128 trainees and 268 cardiovascular team members). Since peaks in COVID-19 disease activity differed by region, questions were structured to ask about feelings of burnout before COVID-19 and during the peak of COVID-19 in their region.

Burnout rates were lower among international cardiology professionals compared to U.S.-based peers. This data will be harder to interpret as each region has its own contributors to burnout that may differ, and there may be some inherent bias in who completed the survey, Mehta said.

Supporting clinician wellness by providing potential solutions to alleviate some of the job pressures associated with burnout has become a strategic priority for the American College of Cardiology, said Mehta, who serves as chair of the ACC's Task Force on Clinician Well-Being.

"Burnout is a metric, but well-being is the goal and what we are striving for," she said. "While we are resilient, these results show that we really need to be focusing on fixing the work environment, including ensuring that we have enough PPE, feeling valued and safe at work, improving team dynamics and efficiencies, which are all essential whether there is COVID-19 or not. Organizations need to focus on improving workforce care not just patient care."

The study is limited in that it relied on respondents' own interpretation of burnout. Mehta and her team will be examining the data more closely to understand gender and career stage differences.

Using more sensitive and frequent repeat testing of a blood test that indicates heart injury to guide the treatment of low-risk patients with symptoms of a possible heart attack resulted in patients being discharged earlier and receiving fewer cardiac stress tests but did not improve patient outcomes after one year, according to research presented at the American College of Cardiology's 70th Annual Scientific Session. In fact, a subset of patients receiving this more sensitive and frequent blood testing protocol were more likely to have a heart attack or to die during the one-year follow-up period compared with patients whose treatment was informed by the results of conventional blood testing procedures.

Troponins are proteins found in heart muscle that are released into the bloodstream when the heart muscle is damaged. Clinicians test for troponin in the blood when a patient visits a hospital emergency room with chest pain or other symptoms. While the detection of troponin in the blood may signal that a patient is having a heart attack, other heart problems, including heart failure or atrial fibrillation, or conditions such as a blood clot in the lungs or kidney disease can also cause elevated troponin levels.

"We wanted to know whether giving physicians greater information about troponin levels within a zero/one-hour repeat-testing protocol would change how they managed patients and whether such changes would lead to improvements in outcomes," said Derek Chew, MBBS, MPH, PhD, professor of cardiology at Flinders University in Adelaide, Australia, and principal investigator of the study. "We found that using high-sensitivity troponin in a rapid repeat-testing protocol, with recommendations for subsequent patient management, may have changed how physicians managed patients, but this did not lead to better outcomes."

Newer, highly sensitive laboratory assays are now routinely used to measure two types of troponin, known as troponin T and troponin I, in the blood. This randomized clinical trial used an assay that can detect levels of troponin T as low as five nanograms per liter (ng/L). By contrast, older, less-sensitive troponin tests accurately detected troponin levels only down to 29 ng/L. Few randomized controlled trials have looked at whether using the newer, more-sensitive troponin tests leads to better outcomes for patients, Chew said.

The study involved 3,378 patients (median age 59 years, 53% male) who visited emergency rooms at four metropolitan centers across South Australia with chest pain or other symptoms of a possible heart attack. Patients were eligible for the study if the results of their initial electrocardiogram, which measures electrical signals in the heart, did not show clear signs that they were experiencing inadequate blood supply to the heart muscle.

The participants were randomly assigned to one of two groups. Participants in the standard-care group received a troponin test on arrival at the emergency department and a second test three hours later. Treating physicians were blinded to the test results below 29 ng/L (i.e., the less-sensitive troponin assay level), in accordance with standards of practice at the time, and subsequent care was at the treating physician's discretion.

In the intervention group, participants also received a troponin test on arrival at the emergency department, but they received a second test sooner--just one hour after the first. The results provided to physicians were unblinded, allowing them to see the troponin result down to a level of 5 ng/L (i.e., the high-sensitivity troponin assay level). Based on the initial high-sensitivity troponin test result and the change in the troponin level over one hour, participants were categorized as "rule out," "rule in" or "further observation" for a heart attack, with guidance for subsequent care provided based on their category. The study's primary endpoint was time to a heart attack or death from any cause during the 12-month follow-up period.

Follow-up data were available for 3,270 participants (108 withdrew from the study by 12 months). For 92% of participants, both initial troponin T tests showed levels below 29 ng/L. Patients in the intervention group were discharged earlier than those in the standard-care group and underwent fewer stress tests (which evaluate how well the heart performs during exercise) and slightly more angiograms (which use X-rays to assess blood flow through the arteries in the heart).

Overall, the researchers found no statistically significant differences in the number of heart attacks or deaths between the two groups during the 12-month follow-up period. However, in the subset of patients whose initial troponin levels were below 29 ng/L, 3.7% of those in the intervention group had a heart attack or died within the follow-up period, compared with 2.3% in the standard-care group. This difference amounted to a 60% increase in the risk of a heart attack or death for this subset of patients.

"This finding may imply that the practice changes observed with the use of a zero/one-hour, high-sensitivity troponin T testing protocol--fewer stress tests and slightly more angiograms--may be associated with an increase in the risk of death or a heart attack within 12 months," Chew said. "However, it is possible that this finding occurred by chance, and therefore it should be interpreted with caution. Overall, the finding may signal the continued utility of functional testing, such as stress tests, and a need for reconsideration of downstream investigations and therapies in the large presenting population with low-level troponin elevations."

People with extremely high levels of triglycerides (a type of fat in the blood) and a specific genetic profile saw a substantial reduction in triglycerides after taking the human monoclonal antibody evinacumab compared with those taking a placebo, in a study presented at the American College of Cardiology's 70th Annual Scientific Session.

Severe hypertriglyceridemia is a rare disorder that causes extremely high levels of triglycerides, an accumulation of fat in the blood that can lead to heart, liver and pancreatic disease. People with severe hypertriglyceridemia commonly have triglyceride levels of 1,000 mg/dL (less than 150 mg/dL is considered normal and above 200 mg/dL is considered high) that cannot be adequately controlled with dietary restrictions or available medications.

"This trial has important clinical implications for this population with severe hypertriglyceridemia," said Robert S. Rosenson, MD, professor of medicine in cardiology and director of metabolism and lipids for the Mount Sinai Health System and the study's lead author. "It also demonstrates the importance of genetic testing in people with severe hypertriglyceridemia because by performing genetic testing you are able to tell which individuals will respond to this therapy and which are unlikely to respond."

Evinacumab is a monoclonal antibody currently approved for treating familial hypercholesterolemia (FH), a condition that causes extremely high cholesterol. Previous clinical trials found that evinacumab reduced triglycerides, as well as LDL or "bad" cholesterol, in people with FH. Evinacumab works by binding to angiopoietin-like protein 3 (ANGPTL3), a protein regulating cholesterol and triglycerides.

To study evinacumab's effects on triglycerides, the new phase 2 trial enrolled 51 patients with hypertriglyceridemia at 17 sites in four countries in North America and Europe. The patients did not have FH and had a history of triglyceride levels of 1,000 mg/dL and prior hospitalization for acute pancreatitis. At the time of screening, patients' triglyceride levels were 500 mg/dL or higher despite maintaining a strict diet. Acute pancreatitis is a common complication of hypertriglyceridemia.

Two-thirds of the trial participants were randomly assigned to receive evinacumab via intravenous infusion at a dosage of 15 mg/kg every four weeks for a total of 24 weeks. One-third received a placebo for the first 12 weeks (the double-blind portion of the study) and then received evinacumab for the second 12 weeks. All participants underwent genetic testing to assess mutations in LPL pathway genes, which provide instructions for making an enzyme called lipoprotein lipase that plays a critical role in breaking down tryglicerides.

At the end of the 12-week placebo-controlled double-blind period, the median triglyceride level dropped by more than 800 mg/dL (57%) in patients taking evinacumab, compared with an overall increase of 50 mg/dL (1.8%) in participants taking a placebo. The magnitude of triglyceride lowering with evinacumab was highly dependent on participants' genetic profile. Those with a double copy of certain mutations in LPL pathway genes had essentially no benefit from evinacumab, whereas patients with a single mutation or no mutations in LPL pathway genes saw triglyceride reductions of around 80%. Among patients with no identifiable LPL mutations, changes in the double-blind treatment and single-blind treatment (primary endpoint) showed a mean reduction in triglycerides of 27.1% and a median reduction of 68.8%.

While other therapies will be needed for patients with the double copy of certain LPL mutations, researchers said these new findings suggest evinacumab may be a promising therapeutic option for those with the appropriate genetic profile.

"Severe hypertriglyceridemia is a severe, unrelenting condition that impairs quality of life," Rosenson said. "Many patients have their first episode of pancreatitis in their teenage years and often end up in intensive care. Most lipid-lowering therapies don't work in these individuals, and that's why we need alternative therapies for them."

Adverse events such as abdominal pain, acute pancreatitis and headache occurred in about 70% of patients in both groups, but there was no significant difference in the rate of adverse events between those taking evinacumab and those taking a placebo. While the trial was not designed to determine an effect on the occurrence of acute pancreatitis, the majority of acute pancreatitis events occurred either when patients were receiving placebo or more than four weeks after completing evinacumab treatment. A separate study is now underway to determine whether evinacumab reduces recurrent pancreatitis by lowering triglycerides.

Rosenson said future studies could investigate evinacumab's potential benefits for patients with elevations in both triglycerides and LDL cholesterol, a combination often seen in patients with diabetes. "By lowering triglycerides by 60-80% and LDL cholesterol by 50% on top of statins and other medications, this agent has an opportunity to impact cardiovascular disease in these very high-risk individuals," Rosenson said.

As a phase 2 trial, the study was limited by its small sample size. Further studies with a broader patient population and larger sample size could further elucidate evinacumab's potential benefits for lowering triglycerides.

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, did not significantly reduce the risk of organ failure or death or improve recovery in patients hospitalized with COVID-19 who are at high risk of developing serious complications compared to placebo, according to data presented at the American College of Cardiology's 70th Annual Scientific Session. The researchers, while acknowledging the results were not statistically significant, said they were encouraged by the lower numbers of organ failure and deaths observed in patients treated with dapagliflozin and by favorable safety data.

COVID-19 can lead to multi-organ failure, especially in patients at high risk for severe illness and complications. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial was the first phase III randomized, controlled clinical trial that was initiated to determine whether dapagliflozin could reduce cardiovascular, kidney and respiratory complications or all-cause death and improve recovery (dual primary endpoints), in patients acutely ill and hospitalized with COVID-19.

Dapagliflozin is an SGLT2 inhibitor that was initially developed as a medication to lower blood sugar levels in patients with Type 2 diabetes, but clinical studies have since demonstrated that it also has significant cardiovascular and kidney benefits, regardless of diabetes status.

"We already know that SGLT2 inhibitors provide organ protection in patients with Type 2 diabetes, heart failure and chronic kidney disease, and these are the exact same patients who if they contract COVID-19 are at high risk to be hospitalized with serious illness and develop complications, such as organ failure," said Mikhail Kosiborod, MD, cardiologist at Saint Luke's Mid America Heart Institute, vice president for Research at Saint Luke's Health System in Kansas City, Missouri, and the study's principal investigator. "Accordingly, we wanted to see if dapagliflozin may also help with organ protection in patients with cardiometabolic risk factors who are acutely ill and require hospitalization due to COVID-19."

A total of 1,250 patients admitted with COVID-19 at 95 sites in the U.S., Brazil, Mexico, Argentina, India, Canada and the U.K. between April 2020 and January 2021 were included in the trial. Patients, who also had risk factors for developing serious complications, including high blood pressure, diabetes, atherosclerotic vascular disease, heart failure or chronic kidney disease, were randomized 1-to-1 to dapagliflozin (10 mg) or placebo once daily. Patients started the treatment as soon as possible (and no later than four days following hospital admission) and continued the treatment for a total of 30 days, even if they were discharged from the hospital. Neither the patient nor the clinician or study personnel knew which treatment patients were receiving.

At 30 days, organ failure or death--one of the study's primary endpoints--occurred in 11.2% of patients who were treated with dapagliflozin and 13.8% of patients treated with placebo. Altogether, 6.6% of patients in the dapagliflozin group died during study follow-up versus 8.6% in the placebo group.

Kosiborod said that for every component of organ failure or death endpoint--respiratory, cardiac, kidney failure or death from any cause--the results appeared to be directionally favorable for dapagliflozin as compared to placebo; however, because they did not reach statistical significance, further study is needed.

"Our study generates a hypothesis that dapagliflozin may offer organ protection in acutely ill patients who are hospitalized with COVID-19, but we were not able to prove this beyond a reasonable doubt because patient outcomes rapidly improved during the study period, making it much harder to accrue enough events and reach statistical certainty," Kosiborod said.

Rapid improvements in the standard of care for patients hospitalized with COVID-19 between spring and summer of 2020 resulted in substantial declines in the number of patients with organ failure or death, he explained. For example, the mortality rate in patients hospitalized with COVID-19 in the U.S. decreased from approximately 25% to 5% between April and August of 2020.

The second primary endpoint of recovery, driven mostly by time to hospital discharge, was similar between patients taking dapagliflozin and placebo. Of importance, dapagliflozin was well-tolerated, with no new safety issues identified.

"There were concerns at the beginning of the pandemic about the safety of SGLT2 inhibitors in patients hospitalized with COVID-19, and some groups were recommending discontinuation of these medications in this setting, even in individuals with chronic conditions in which they have known benefits, such as Type 2 diabetes and heart failure. Everyone was doing their best to make recommendations for what they felt was the safest approach in a data-free zone at that time," Kosiborod said. "Our findings show that dapagliflozin is well-tolerated in patients hospitalized with COVID-19, with no new safety issues being observed. This should have implications for clinical practice given that our results do not support discontinuation of SGLT2 inhibitors in this setting, as long as patients are monitored."

Overall, there were numerically fewer serious adverse events in patients receiving dapagliflozin versus placebo, researchers reported. Two non-severe cases of diabetic ketoacidosis were observed in the trial, both in the dapagliflozin group and in patients with prior history of Type 2 diabetes.

"Our study opens the door to asking additional questions," Kosiborod said. "The idea for DARE-19 was quite unorthodox when we started--everyone was concentrating on antivirals and anti-inflammatory drugs, so it is fascinating to hypothesize that SGLT2 inhibitors may provide organ protection in acute illness. This should inform future clinical science and hopefully lead to further investigations."

Older patients hospitalized with acute heart failure who participated in a novel 12-week physical rehabilitation (rehab) program tailored to address their specific physical impairments had significant gains not only in physical functioning but also quality of life and depression compared with those receiving usual care, regardless of their heart's ejection fraction, according to a new study presented at the American College of Cardiology's 70th Annual Scientific Session. Participation in the program, however, did not significantly reduce rehospitalizations during the six-month follow up.

Heart failure, which happens when the heart can't pump blood the way it should because it is too weak or stiff, is the leading cause of hospitalizations in people 65 and older. Many of these patients are never able to return to their previous level of functioning--resulting in reduced independence and increased risk of returning to the hospital or dying.

"These patients have persistently poor outcomes with frequent rehospitalizations, poor quality of life, high rates of dying and high health care costs," said Dalane W. Kitzman, MD, professor of cardiovascular medicine and geriatrics/gerontology at Wake Forest School of Medicine and the study's lead author. "Despite many efforts to improve outcomes in these patients, most studies testing a wide range of medications, devices and strategies have been negative. This suggested to us that we were overlooking an important factor contributing to these poor outcomes, and we suspected the missing factor might be severe physical dysfunction, which is generally not addressed in heart failure management."

In an earlier pilot study, Kitzman and colleagues found that older patients admitted to the hospital with acute heart failure had profound deficits in all domains of physical function, including their balance, mobility and strength, not just in endurance, which would have been expected. Nearly all of these patients (97%) were considered frail or prefrail.

"Even before they are hospitalized, these patients already have lower physical functioning due to both aging and their chronic heart failure, and when their heart failure worsens, their physical function deteriorates further and this can then be exacerbated by the hospital experience and bed rest," Kitzman said. "This sequence of events leading to marked impairments in all domains of physical function and its impact on patient outcomes has been largely overlooked."

With these insights, the REHAB-HF rehabilitation intervention was developed and designed to correct deficits in balance, mobility and strength. REHAB-HF seeks to enhance effectiveness and avoid injuries that can occur when frail older persons undertake traditional cardiac rehab programs that are more focused on endurance. The program was tailored to each patient's specific needs and adjusted to their ability level as they progressed. Unlike traditional cardiac rehab programs that typically start six weeks after a hospitalization, the REHAB-HF program started early--during the patient's hospital stay if possible--and transitioned to three outpatient sessions per week for 12 weeks following hospital discharge. The aim of the current REHAB-HF trial was to evaluate whether this novel rehabilitation program could improve physical function (primary outcome) and rehospitalizations (secondary outcome) when compared to usual care that could include physician-ordered physical therapy or traditional cardiac rehab.

A total of 349 patients across seven different hospitals, including four community hospitals, were enrolled in the study. Patients ranged in age from 60-99 years; over half were women and 49% were from underrepresented racial or ethnic minority groups. Notably, 53% had heart failure with preserved ejection fraction (HFpEF). Overall, they had an average of five comorbidities, most commonly high blood pressure, diabetes, obesity, lung disease and kidney disease, which may also contribute to declines in physical function.

At the three-month follow-up, compared with participants randomized to receive usual care, those in the intervention group had notable and significant improvements in physical functioning and quality of life across all the assessments used. For example, the Short Physical Performance Battery, a standard measure of physical function in older adults, improved by 1.6 units--more than twofold greater than the minimum amount that is meaningful to patients. On the six-minute walk test, they were able to walk 34 meters farther, a large improvement compared to very low function at baseline. Participant scores on the Kansas City Cardiomyopathy Questionnaire, which measures the patient's perception of their health status, and a separate depression survey also showed large improvements. The improvements in physical function in the REHAB-HF intervention group were even greater when compared to the subset of usual care patients who had received traditional physical therapy and/or cardiac rehab as part of their physician's orders, further supporting the effectiveness of the REHAB-HF intervention.

At six months, 83% of patients were still doing their exercises, which Kitzman said bodes well for long-term adherence. However, there were no statistically significant differences in clinical events, including rates of readmission for any reason, with 194 and 213 rehospitalizations occurring in the intervention group and usual care control group, respectively. Heart failure-related hospitalizations were also no different (94 vs. 110) at six months. There were numerically more deaths among people in the rehab group (21 vs. 16), but this was not statistically significant; researchers said this result may have been due to chance.

"The study was not large enough to really look at clinical events. But patient preference surveys show that older patients often value improved function and quality of life independently of rehospitalization and death," Kitzman said. "By improving quality of life and physical functioning, the patient feels better, which is a positive outcome for patients."

Kitzman and his collaborators at Duke University School of Medicine and Thomas Jefferson School of Medicine are now investigating whether certain subgroups of patients (for example, those with HFpEF) saw more benefits, which could inform a subsequent larger trial powered to definitively examine effects on clinical events.

Rivaroxaban, in addition to low-dose aspirin, significantly reduced the occurrence of total severe events of the heart, limb or brain and issues related to other vascular complications in patients with symptomatic peripheral artery disease (PAD) who underwent lower extremity revascularization, a procedure to open blocked arteries in the leg. The findings, presented at the American College of Cardiology's 70th Annual Scientific Session, expand on earlier data and underscore the broad absolute benefits of this strategy in this high-risk patient population, researchers said.

"To our knowledge, this is the first time that the addition of low-dose rivaroxaban to aspirin has been clearly shown to reduce the occurrence of both first and total adverse events in patients with PAD who have undergone lower extremity revascularization but remain at high risk for a heart attack, stroke or recurrent arterial blockage in a limb," said Rupert Bauersachs, MD, director of vascular medicine at the Darmstadt Clinic in Germany and lead author of the study. "The benefits we saw in the trial for first events were statistically significant and entirely consistent with those for total events. Rivaroxaban 2.5 mg twice daily with aspirin should be considered as adjunctive therapy after revascularization to reduce first and subsequent adverse outcomes."

An estimated 10 million U.S. adults and 200 million people worldwide have PAD, which is often associated with leg pain, difficulty walking and poor circulation that can lead to non-healing wounds and a high rate of limb loss. People with PAD are at very high risk for serious complications, including acute limb ischemia--similar to a heart attack or stroke of the leg--that can lead to limb amputation or death if not treated quickly. Patients with symptomatic PAD are commonly treated with procedures to open arteries in the leg to improve symptoms and prevent limb loss, but they remain at very high risk for adverse events. Overall, about 1 in 4 patients with symptomatic PAD require a repeat procedure to open a blocked leg artery.

"There is a need for greater awareness that PAD is a distinct disease state and that patients with PAD have a high risk for cardiovascular adverse events and are generally a very vulnerable population, especially in the post-revascularization setting," Bauersachs said. "Care for these patients is often fragmented because the surgeon who performs the revascularization may not follow them for complications or recurrences. They deserve to receive optimal treatment to reduce the risk of recurrences."

The randomized, double blind, international trial, known as VOYAGER PAD, enrolled 6,564 patients in 34 countries who had PAD and had undergone lower extremity revascularization. The patients' median age was 67 years and 74% were men. Patients were randomly assigned to receive rivaroxaban or a placebo in addition to daily aspirin. The trial was double blinded, meaning that neither the patients nor their doctors knew who was receiving rivaroxaban and who was receiving the placebo. The trial's primary endpoint was timed to the first event of a composite of acute arterial blockage in the leg (called acute limb ischemia), leg amputation due to blood-vessel disease, heart attack, stroke or death due to cardiovascular causes. Another prespecified endpoint was the total number of vascular events, including recurrent primary endpoint events as well as other vascular events like blood clots in the leg veins or lungs or the need for repeat vascular procedures. The median follow-up time was 28 months after patients underwent revascularization.

The research team reported in a late-breaking clinical trial presented at ACC.20/WCC that the trial met its primary endpoint, with a 15% statistically significant reduction in the risk of a first major adverse limb or cardiovascular event seen in patients who received rivaroxaban compared with those who received the placebo. The current study reports on the total number of vascular events with over 4,700 occurring in the 6,564 randomized over three years.

"There were 342 fewer adverse events in the rivaroxaban group than in the placebo group, which translates to an absolute reduction in risk of 12.5%," Bauersachs said. "In a high-risk population, that is a big gain in avoiding the need for patients to come back with vascular complications."

The 6,564 study participants experienced a total of 4,714 vascular events during the study period with 2,301--or about one-third--experiencing at least one vascular event, Bauersachs said.

"So, during approximately three years of follow-up, about 2-3 out of 6 patients with PAD had a vascular event in spite of high utilization of background medical therapy. This overall rate of vascular events is eye-opening and speaks to the high vulnerability of this patient population," Bauersachs said. "First events are just the tip of the iceberg."

A limitation of the study is that the trial was designed to assess the occurrence of first adverse events following lower extremity revascularization, Bauersachs said. Therefore, in a double blinded trial, patients may come off study treatment or go on to other therapies after an event, which can attenuate the observed benefit. Assessment of the total number of adverse events, however, was a prespecified secondary endpoint and despite this limitation, the findings were statistically significant and robust in absolute terms.

In patients who had a coronary stent inserted after experiencing the most severe type of heart attack, the use of a technique that measures blood flow and pressure through a partially blocked artery to determine if a second stenting procedure is needed did not improve outcomes and was more costly than using angiography, or a heart X-ray, alone to guide the procedure, according to research presented at the American College of Cardiology's 70th Annual Scientific Session.

"The strategy of using fractional flow reserve (FFR) to guide the stenting procedure is not superior to the standard technique of using angiography to treat additional partially blocked arteries," said Etienne Puymirat, MD, professor of cardiology at the University of Paris, director of intensive care at the Georges Pompidou Hospital in Paris and principal investigator of the study. "In addition to having no benefit, we have also shown that, based on costs in France, the FFR-guided strategy is more expensive."

Most heart attacks are caused by a blood clot in an artery to the heart that's been narrowed by a buildup of fatty deposits, or plaque. In the most severe type of heart attack, known as a STEMI heart attack, an artery to the heart is completely blocked, causing the death of some heart tissue.

The current study, known as the FLOWER-MI trial, was the first to do a head-to-head comparison of outcomes in STEMI patients with multi-vessel disease who underwent either FFR-guided stenting or stenting guided by angiography alone.

FFR is a measure of blood flow and pressure through a narrowed coronary artery. It is performed during angiography to determine if the stenosis, or narrowing of the artery, is significant and to guide the stenting procedure. Previous studies have shown that STEMI patients treated with FFR-guided stenting had better outcomes than those treated with medication alone, without the insertion of a stent.

Stenting, also known as coronary angioplasty or percutaneous coronary intervention (PCI), is a minimally invasive procedure in which a flexible tube (catheter) is threaded through a coronary artery under local anesthesia. At the site of the blockage, a tiny balloon at the tip of the catheter is inflated to unblock the artery and a stent, a tiny mesh tube coated with medication, is inserted to prop the artery open, restoring blood flow to the heart. Clinicians typically use angiography to assess the extent of blockage in the coronary artery and guide the stenting procedure.

The trial, conducted at 41 centers in France, enrolled 1,171 patients who had a stent inserted into a blocked coronary artery after a STEMI heart attack and who also had a second coronary artery that was at least 50% blocked. The patients' average age was 62 years and 83% were men. Immediately after their first stenting procedure, all patients were randomly assigned to undergo a second stenting procedure in the partially blocked artery, guided either by FFR or by angiography alone. The second procedure was performed within five days of the first during the same hospitalization.

After 12 months, 5.5% of patients in the FFR-guided group had died, had another non-fatal heart attack or had undergone an additional stenting procedure, compared with 4.2% of those in the angiography-guided group, a non-statistically significant difference. Moreover, the FFR-guided procedure was more expensive than the one guided by angiography alone.

The incidence of major adverse cardiovascular events in both groups of patients was considerably lower than the researchers expected, Puymirat said. "These patients were at high cardiovascular risk because of having multi-vessel disease," he said. "Using data from previous trials and registries in this population, we estimated that about 15% of patients would have an adverse event within one year, but in our study the rate was 5% at one year."

The study failed to meet its primary endpoint, a composite of death from any cause, non-fatal heart attack, or urgent need for an additional stenting procedure within 12 months. A secondary endpoint looking at cost-effectiveness favored the use of angiography alone. However, the cost-effectiveness analysis was based on the costs of the two treatment approaches in France and might not be applicable in other countries, Puymirat said.

The researchers will continue to follow the patients in the study for another two years.

This study was simultaneously published online in the New England Journal of Medicine at the time of presentation. The study was funded by a grant from the French Ministry of Health with additional support from Abbott.

Puymirat will be available to the media in a virtual press conference on Sunday, May 16, at 12:15 p.m. ET / 16:15 UTC.

Puymirat will present the study, "Fractional Flow Reserve-guided Versus Angio-guided Multivessel Revascularization In ST-Elevation Myocardial Infarction Patients. The FLOWER-MI Randomized Trial," on Sunday, May 16, at 10:45 a.m. ET / 14:45 UTC, virtually.

Image fusion is a process that can enhance the clinical value of medical images, improving the accuracy of medical diagnoses and the quality of patient care.

Researchers at the College of Data Science Software Engineering at China's Qingdao University, have developed a new 'multi-modal' image fusion method based on supervised deep learning that enhances image clarity, reduces redundant image features and supports batch processing. Their findings have just been published in KeAi's International Journal of Cognitive Computing in Engineering.

Author Yi Li explains: "Most medical images have unilateral or limited information content; for instance, focus positions vary which can make some objects appear blurred. Having important information scattered across a number of images can hamper a doctor's judgment. Image fusion is an effective solution - it automatically detects the information contained in those separate images and integrates them to produce one composite image."

Researchers are increasingly turning to deep learning to improve image fusion. Deep learning, a subset of machine learning, draws on artificial neural networks that are designed to imitate how humans think and learn. That means it is capable of learning from data that is unstructured or unlabelled.

However much of the current research focuses on the application of deep learning in single image fusion processing. Studies that use it for multi-image batch processing are much rarer.

Li explains: "Medical images have specific practical requirements, including information richness and high clarity. During our study, we used successful image fusion results to build an image-training database. We were then able to use that database to fuse medical images in batches."

Li adds: "Our method also enhances the clarity of MRI, CT and SPECT image fusion, improving the accuracy of medical diagnosis. We have achieved state-of the-art performance in terms of both visual quality and quantitative evaluation metrics. For example, the fused images we produced look more natural, and have sharper edges and higher resolution. In addition, detailed information and features of interest are better preserved."

ATS 2021, New York, NY - A weighted "lottery" designed to increase access to the antiviral drug remdesivir during the May-July 2020 COVID-19 surge for those most affected by the coronavirus, including members of the Black, Latinx and indigenous communities, led to more equitable distribution of the badly needed medication, according to research presented at the ATS 2021 International Conference.

At a time when supplies of COVID-19 medications were scarce, Douglas B. White, MD, MAS, vice chair and professor of critical care medicine, UPMC endowed chair for ethics in critical care medicine and director of the Program on Ethics and Decision Making in Critical Illness, University of Pittsburgh School of Medicine, and colleagues, convened a multi-institution consortium of experts to develop a weighted lottery, in which some patients would be given higher priority for receiving remdesivir while others would be given lower priority.

Consortium members had expertise in bioethics, economics, health disparities, medicine, pharmacy and health law. They assigned more weight to patients from disadvantaged communities and essential workers, and less weight to patients expected to die within a year from a terminal condition and those with severe respiratory failure.

The lottery was implemented at 23 hospitals across the UPMC health system during periods of drug shortage. The team identified eligible patients using an electronic health record- and telephone-based screening system. They calculated the number of potentially eligible patients each week, based on the number of patients who were eligible the previous week. Using the weighting system previously described, a drug allocation team met each day to determine each eligible patient's chance of receiving the drug, and then used a random number generator to run the lottery.

Overall, 61 percent of the available remdesivir was allocated to patients who were from disadvantaged neighborhoods and/or were essential workers. These individuals made up 56 percent of the COVID-19 patient population.

"We showed that in the maelstrom of a pandemic it is possible to deploy an organized allocation strategy that promotes both equity and clinical benefit," said Dr. White.

"This is a major improvement over the first-come, first-served approach that many hospitals have used; that approach is likely to worsen disparities for those with access-to-care barriers. Among those most affected would be persons with disabilities that limit their mobility and those without health insurance, who may delay seeking care due to financial concerns."

He noted that the weighted lottery also allows planners to give priority to certain groups, such as those who are most likely to benefit and those who have been disproportionately affected by the pandemic, such as individuals from hard-hit communities.

"It was our goal from the outset to develop a framework and process that any hospital can use," stated Dr. White. The team also developed a detailed protocol that describes the steps to carry out the lottery, which can be found here.

The researchers concluded that it is best to implement the lottery on a centralized, regional level, rather than hospital-by-hospital. "It is far more efficient to conduct one lottery for many hospitals than have each hospital conduct its own lottery. This approach can simultaneously accomplish fair allocation and rapid learning, because the lottery creates a natural experiment in which some patients receive the scarce drug while others do not. Researchers can use the lottery's registry to assess the effectiveness of the drug." This is described in detail in this article.

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WINSTON-SALEM, N.C. - May 16, 2021 - Heart failure (HF) - when the heart can't pump enough blood and oxygen through the body - affects approximately 6.2 million adults in the United States and is the primary cause of hospitalization in the elderly. Unfortunately, older adults with heart failure often have poor outcomes resulting in reduced quality of life, high mortality and frequent rehospitalizations.

Despite many efforts to improve the prognosis in these patients, most previous studies testing a wide range of interventions were not successful.

Scientists from the Wake Forest, Duke University and Thomas Jefferson schools of medicine tried a different approach - tailoring rehabilitation treatment to the individual and beginning it while the patient was still recovering in the hospital, which is not standard care for these older HF patients.

Using this novel approach, the researchers found that hospitalized older patients with acute heart failure had significant gains in physical function, including balance, mobility, strength and endurance, compared with those receiving usual care, regardless of their heart's squeezing ability (ejection fraction).

The findings are published in the May 16 issue of the New England Journal of Medicine and reported simultaneously at the annual meeting of the American Association of Cardiologists. The study was funded by the National Institute on Aging.

"In an earlier pilot study, we had observed these patients had marked physical dysfunction, with 97% being frail or pre-frail," said the study's lead author, Dalane Kitzman, M.D., professor of cardiovascular medicine and gerontology at Wake Forest School of Medicine, part of Wake Forest Baptist Health.

"And the types of dysfunction were not commonly associated with heart failure - problems with balance, mobility and strength, as well as endurance. One-third could not get out of a chair without using their arms or other assistance and their endurance was twice as bad as similarly aged patients with HF who had not been hospitalized. We also found high rates of depression and cognitive dysfunction, which were usually unrecognized clinically."

Kitzman's team hypothesized that these patients' physical function, which was already compromised due to age and chronic heart failure, worsened and was further exacerbated by their hospital experience and bedrest, and the deficits often persisted after discharge.

To test their theory, they assembled a team of physical-rehabilitation experts to develop the REHAB-HF program, which was specifically designed to meet the unique needs of these patients. The intervention began as early in the hospital stay as possible, transitioned to an outpatient facility for three sessions a week for 12 weeks, and then transitioned to exercise at home, Kitzman said.

This Phase 2 trial included 349 patients, age 65 and older, of whom more than 50% were women and nearly 50% were non-white, at seven medical centers, including four community hospitals.

At three-month follow-up, the scientists found large, statistically significant improvements in physical function as determined through standard measurements of balance, mobility, strength and endurance. Also, rates of frailty and depression declined.

Notably, at six-month follow-up, 83% of patients were still exercising on their own, suggesting they may continue to do so long-term, Kitzman said.

However, at six months there were no statistically significant differences in clinical events such as rates of readmission for any reason, with 194 and 213 rehospitalizations occurring in the intervention group and usual care control group, respectively. Heart failure-related hospitalizations also were no different at six months. There were numerically more deaths among people in the rehab group, but this was not statistically significant and may have been due to chance.

"The study was not large enough to really look at clinical events" Kitzman said. "But by improving quality of life and physical functioning, the patient feels better, which is a positive outcome."

Hamilton, ON (May 15, 2021) - A simple surgery saves patients with heart arrhythmia from often-lethal strokes, says a large international study led by McMaster University.

Researchers found that removing the left atrial appendage -- an unused, finger-like tissue that can trap blood in the heart chamber and increase the risk of clots -- cuts the risk of strokes by more than one-third in patients with atrial fibrillation.

Even better, the reduced clotting risk comes on top of any other benefits conferred by blood-thinner medications patients with this condition are usually prescribed.

"If you have atrial fibrillation and are undergoing heart surgery, the surgeon should be removing your left atrial appendage, because it is a set-up for forming clots. Our trial has shown this to be both safe and effective for stroke prevention," said Richard Whitlock, first author of the study.

"This is going to have a positive impact on tens of thousands of patients globally."

Whitlock is a scientist at the Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences (HHS); a professor of surgery at McMaster, the Canada Research Chair in cardiovascular surgical trials, a cardiac surgeon for HHS, and is supported by a Heart and Stroke Foundation career award.

The co-principal investigator of the study is Stuart Connolly who has also advanced this field by establishing the efficacy and safety of newer blood thinners. He is a professor emeritus of medicine at McMaster, a PHRI senior scientist and a HHS cardiologist.

"The results of this study will change practice right away because this procedure is simple, quick and safe for the 15 per cent of heart surgery patients who have atrial fibrillation. This will prevent a great burden of suffering due to stroke," Connolly said.

The study results were fast tracked into publication by The New England Journal of Medicine and presented at the American College of Cardiology conference today.

The study tracked 4,811 people in 27 countries who are living with atrial fibrillation and taking blood thinners. Consenting patients undertaking cardiopulmonary bypass surgery were randomly selected for the additional left atrial appendage occlusion surgery; their outcomes compared with those who only took medicine. They were all followed for a median of four years.

Whitlock said it was suspected since the 1940s that blood clots can form in the left atrial appendage in patients with atrial fibrillation, and it made sense to cut this useless structure off if the heart was exposed for other surgery. This is now proven to be true.

Atrial fibrillation is common in elderly people and is responsible for about 25 per cent of ischemic strokes which are caused when blood clots block arteries supplying parts of the brain. The average age of patients in the study was 71.

"In the past all we had was medicine. Now we can treat atrial fibrillation with both medicines and surgery to ensure a much better outcome," said Whitlock.

He said that the current study tested the procedure during cardiac surgery being undertaken for other reasons, but the procedure can also be done through less invasive methods for patients not having heart surgery. He added that future studies to examine that approach will be important.

Whitlock said the left atrial appendage is a leftover from how a person's heart forms as an embryo and it has little function later in life.

"This is an inexpensive procedure that is safe, without any long-term adverse effects, and the impact is long-term."