Tag: Muscle

Major discovery improves the understanding of brain fog associated with Long COVID

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Today, a team of scientists from Trinity College Dublin and investigators from FutureNeuro announced a major discovery that has profound importance for our understanding of brain fog and cognitive decline seen in some patients with Long COVID.

In the months after the emergence of the novel coronavirus SARS-CoV2 in late 2019 a patient-reported syndrome termed Long-COVID began to come to the fore as an enduring manifestation of acute infection.

Long COVID has up to 200 reported symptoms to date, but in general patients report lingering symptoms such as fatigue, shortness of breath, problems with memory and thinking and joint/muscle pain. While the vast majority of people suffering from COVID-19 make a full recovery, any of these symptoms that linger for more than 12 weeks post infection can be considered Long COVID.

Long COVID has now become a major public health issue since the outbreak of the pandemic in 2020. While international incidence rates vary, it is estimated to affect up to 10% of patients infected with the SARS-CoV2 virus. Of these patients suffering from Long-COVID, just under 50% of them report some form of lingering neurological effect such as cognitive decline, fatigue and brain fog.

Now, the findings reported by the Trinity team in the top international journal Nature Neuroscience showed that there was disruption to the integrity of the blood vessels in the brains of patients suffering from Long COVID and brain fog. This blood vessel “leakiness” was able to objectively distinguish those patients with brain fog and cognitive decline compared to patients suffering from Long-COVID but not with brain fog.

The team led by scientists at the Smurfit Institute of Genetics in Trinity’s School of Genetics and Microbiology and neurologists in the School of Medicine have also uncovered a novel form of MRI scan that shows how Long-COVID can affect the human brain’s delicate network of blood vessels. 

For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system may be the key drivers of brain fog associated with Long COVID. This is critically important, as understanding the underlying cause of these conditions will allow us to develop targeted therapies for patients in the future,”

Prof. Matthew Campbell, Professor in Genetics and Head of Genetics at Trinity, and Principal Investigator at FutureNeuro

This project was initiated by a rapid response grant funded by Science Foundation Ireland (SFI) at the height of the pandemic in 2020 and involved recruiting patients suffering from the effects of Long-COVID as well as patients who were hospitalised in St James’ Hospital.

“Undertaking this complicated clinical research study at a time of national crisis and when our hospital system was under severe pressure is a testament to the skill and resource of our medical trainees and staff. The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions. It also confirms that the neurological symptoms of Long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain,” said Prof. Colin Doherty, Professor of Neurology and Head of the School of Medicine at Trinity, and Principal Investigator at FutureNeuro.

Moving beyond COVID-19

In recent years, it has become apparent that many neurological conditions such as Multiple sclerosis (MS) likely have a viral infection as the initiating event that triggers the pathology. However, proving that direct link has always been challenging.

Prof. Campbell added: “Here, the team at Trinity was able to prove that every patient that developed Long-COVID had been diagnosed with SARS-CoV2 infection, because Ireland required every documented case to be diagnosed using the more accurate PCR-based methods. The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game-changing and is under active investigation by the team.”

Dr Chris Greene, Postdoctoral research fellow and first author of the study, added: “Our findings have now set the stage for further studies examining the molecular events that lead to post-viral fatigue and brain fog. Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalizingly close to understanding how and why they cause neurological dysfunction in patients.”

The research was supported by Science Foundation Ireland, the European Research Council and FutureNeuro, the SFI Centre for rare and chronic neurological, neurodevelopmental and neuropsychiatric conditions.

Source:

Journal reference:

Greene, C., et al. (2024). Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nature Neuroscience. doi.org/10.1038/s41593-024-01576-9.

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February 22, 2024
Study reveals unexpected link between cell membrane damage and cellular senescence

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Our cells are surrounded by a fragile membrane that’s only 5 nanometers thick, 1/20 of a soap bubble. Cells are easily damaged by physiological activities, including muscle contraction and tissue injury. To cope with such damage, cells are equipped with mechanisms that can repair membrane damage to a certain degree.

Mechanical damage to the cell membrane was previously believed to trigger two simple cellular outcomes: recovery or death. In this study, however, the researchers uncovered a third outcome – cellular senescence.

“When I started this project, I simply aimed to understand the repair mechanisms of damaged cell membrane,” recalls Professor Keiko Kono, head of the Membranology unit and senior author of this study, which involved multiple members from the unit, including Kojiro Suda, Yohsuke Moriyama, Nurhanani Razali and colleagues. “Unexpectedly, we ended up discovering that cell membrane damage, in a sense, switches cell fate.”

The key to determining cell fate is the extent of damage and subsequent calcium ion influx. The thin cell membrane damage can be easily repaired, allowing the cells to continue cell division without any trouble. The highest level of cell membrane damage induces cell death. However, a middle level of cell membrane damage turns the cells into senescent cells several days later, even though membrane resealing seems successful.

Cancer cells divide unlimitedly. In contrast, non-cancerous normal cells have a limited capacity for cell division – around 50 times before division is irreversibly stopped, and the cells enter a state known as cellular senescence. Senescent cells are still metabolically active, but unlike young and healthy cells, they produce various secretory proteins that upregulate immune responses in both nearby tissues and distant organs. This mechanism can induce both beneficial and detrimental changes in our body, including acceleration of wound healing, cancer promotion, and aging. During the last decade, numerous studies have reported that senescent cells exist in animal bodies, including humans, and that the removal of senescent cells can rejuvenate body functions in experimental animals. However, the cause of cell senescence in the human body remains a controversial topic.

The gene expression profile and bioinformatics suggested that cell membrane damage explains the origin of senescent cells in our bodies, specifically the ones near damaged tissues.”

Professor Keiko Kono, Senior Author

The best-established inducer of cellular senescence is repeated cell division. Many other stresses also induce cellular senescence in a laboratory setting, such as DNA damage, oncogene activation, and epigenetic changes. The long-standing dogma in the research field was that various stresses induce cellular senescence ultimately via the activation of DNA damage response. However, the authors uncovered that cell membrane damage induces cellular senescence via a different mechanism that involves calcium ions and the tumor suppressor gene p53. These findings may contribute to develop a strategy to achieve healthy longevity in the future.

Source:

Okinawa Institute of Science and Technology (OIST) Graduate University

Journal reference:

Suda, K., et al. (2024). Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts. Nature Aging. doi.org/10.1038/s43587-024-00575-6.

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February 22, 2024
Groundbreaking study sheds light on the potential of the heart to achieve self-repair and regeneration

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A groundbreaking scientific study published in Nature Cardiovascular Research has unveiled a remarkable discovery that may have far-reaching implications for the treatment of heart disease.

The intensive investigations utilizing single-cell genomics and genetic experiments were conducted by a team of renowned scientists in theCardiomyocyte Renewal Laboratory and McGill Gene Editing Laboratory at The Texas Heart Institute, including James F. Martin Vivian L. Smith Chair in Regenerative Medicine and Vice Chairman and Professor of Molecular Physiology and Biophysics at Baylor College of Medicine, and co-first authors Xiao Li, PhD, and Rich Gang Li, PhD. Titled “YAP Induces a Neonatal Like Pro-Renewal Niche in the Adult Heart,” this research sheds light on the potential of the human heart to achieve self-repair and regeneration.

Heart disease remains a leading cause of death worldwide, with myocardial infarction, also known as a heart attack, causing irreparable damage to cardiac muscle cells. While current treatments focus on alleviating symptoms and improving blood flow, they fall short in addressing the crucial issue of lost cardiomyocytes (CMs), leading to further complications such as heart failure. However, this groundbreaking study offers hope for a paradigm shift in regenerative medicine.

Heart disease remains a leading cause of death worldwide, with myocardial infarction, also known as a heart attack, causing irreparable damage to cardiac muscle cells. While current treatments focus on alleviating symptoms and improving blood flow, they fall short of addressing the crucial issue of lost cardiomyocytes (CMs), leading to further complications such as heart failure. However, this groundbreaking study offers hope for a paradigm shift in regenerative medicine.

Contrary to longstanding beliefs, the study reveals that regeneration of CMs requires a complex microenvironment, where a dynamic synergy between CMs, resident immune cells, and cardiac fibroblasts is the driving force behind cardiac renewal. Through intricate signaling mechanisms, these cell types coordinately instruct and support each other, facilitating CM proliferation and effectively repairing damaged heart tissue.

“Understanding heart regeneration on a molecular level is an important step towards developing innovative therapeutics that can facilitate CM regeneration,” said the team in their lay summary. “Our study challenges the existing paradigm, suggesting that targeting the microenvironment rather than a specific cell type is instrumental in healing the injured heart.”

The implications of this groundbreaking discovery are immense, offering glimpses of a future where heart disease may no longer be an irreversible condition but a challenge that can be overcome through medical intervention. The potential for developing novel therapies that leverage the body’s innate regenerative capacity holds great promise for millions of individuals affected by heart disease worldwide.

“YAP Induces a Neonatal Like Pro-Renewal Niche in the Adult Heart” is a milestone in cardiac research. It unlocks a new avenue for scientific exploration and fosters hope for a future where damaged hearts can mend themselves. This remarkable study, published in a prestigious journal like Nature Cardiovascular Research, confirms the significance and impact of these findings.

Source:

Journal reference:

Li, R. G., et al. (2024). YAP induces a neonatal-like pro-renewal niche in the adult heart. Nature Cardiovascular Research. doi.org/10.1038/s44161-024-00428-w.

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February 15, 2024
Trial investigates efficacy of online supervised group mental and physical rehabilitation program for long COVID patients
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In a recent study published in the BMJ, researchers evaluated the efficacy of an online supervised group mental and physical rehabilitation program in adults with long COVID.

Study: Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial. Image Credit: Dmitry Demidovich/Shutterstock.com

Background

Over 17 million people in the European region of the World Health Organization (WHO) may have experienced coronavirus disease 2019 (COVID-19) symptoms longer than four weeks. Common symptoms of this multisystem condition, known as long COVID or post-COVID-19 condition, include muscle aches, fatigue, dyspnea, and cognitive dysfunction that can profoundly impact quality of life, societal participation, and economic productivity. The pathophysiology of long COVID has not been fully characterized.

As such, current medical management and treatments have limited efficacy. The biopsychosocial care model may improve outcomes for long COVID patients. Multicomponent mental and physical rehabilitation could improve fatigue, quality of life, and breathlessness. So far, few quasi-experimental studies evaluated exercise-based interventions for individuals with long COVID, with no definitive, high-quality evidence.

About the study

In the present study, researchers evaluated the clinical effectiveness of a group rehabilitation program for people with long COVID. The rehabilitation exercise and psychological support after COVID-19 infection (REGAIN) was a multi-center, parallel-group, pragmatic, randomized controlled trial. Participants were recruited in England and Wales. Adults (26-86 years) discharged at least three months after hospitalization with COVID-19 who had ongoing mental and physical sequelae were recruited.

Subjects were excluded if they had severe mental health problems, contraindications to exercise training, or were enrolled in other rehabilitation programs. A baseline questionnaire was administered before randomization to REGAIN or usual care. Usual care participants received the best practice usual care; this involved an online consultation with a trained practitioner, wherein generic advice was provided on recovery and physical activity.

The REGAIN intervention was an eight-week, supervised, home-based, group rehabilitation program, providing online consultation with a REGAIN practitioner. REGAIN participants joined weekly live online group exercise and psychological support sessions. Equipment-free, supervised, personalized exercise sessions were delivered in online groups to improve fatigue, cardiovascular fitness, balance, and strength and restore confidence in daily living activities.

Psychological support sessions were aimed at augmenting psychological capability and increasing COVID-19-related knowledge and its impact on everyday life. The primary outcome of the study was health-related quality of life, determined using the patient-reported outcomes measurement information system (PROMIS). Secondary outcomes included dyspnea, cognitive function, physical activity, anxiety, depression, and general health, among others. Outcomes were assessed at three, six, and 12 months.

Findings

Of over 39,000 people invited to participate between January 2021 and July 2022, 1,043 expressed interest. Following exclusions, 298 and 287 subjects were randomized to REGAIN and usual care, respectively. Most participants were female (52%), White (88%), and obese/overweight (88%). One-third of participants required intensive care during COVID-19 hospitalization.

The average time from discharge to randomization was 323 days. The baseline health-related quality of life was low; around 40% had low physical activity. More than a third of participants could not work due to long COVID. Primary outcome data were available for 80% of REGAIN and 86% of usual care participants. The health-related quality of life improved more for REGAIN participants than usual care recipients at three months.

There was a significant group difference in health-related quality of life, primarily driven by three PROMIS sub-scores – fatigue, depression, and pain interference. While the effect of the intervention was not evident at six months, it was sustained at 12 months. REGAIN participants had increased odds of being more physically active than usual care recipients. At three months, 7% more REGAIN subjects met the physical activity guideline (> 150 minutes of moderate-intensity activity per week).

Furthermore, more REGAIN participants reported feeling much better compared to three months than usual care subjects. Adverse events were reported in both groups. Most serious adverse events were related to hospitalization or extended stay at the hospital. Two adverse events were related to the REGAIN intervention. One serious adverse event was possibly related to the intervention. Post-exertional exacerbation of symptoms was not observed.

Conclusions

In sum, the REGAIN intervention was clinically effective in improving health-related quality of life for adults with post-COVID-19 condition compared to usual care at three months post-randomization. This effect was mainly due to improvements in pain interference, fatigue, and depression. Moreover, the effect was sustained at 12 months. In both groups, there were improvements in the overall quality of life and other well-being indices.
Journal reference:

Gordon McGregor, Harbinder Sandhu, Julie Bruce, et al. Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial. BMJ, 2024. doi: 10.1136/bmj-2023-076506
https://www.bmj.com/content/384/bmj-2023-076506
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February 12, 2024
Air Force cadets’ nutrition knowledge linked to success in gravitational acceleration test, study finds

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In a recent study published in Scientific Reports, researchers explored how nutrition knowledge, physical strength and activity, and body composition are related to whether Air Force cadets lose consciousness during the Gravitational Acceleration Test (G-test).

The findings indicate that cadets who remained conscious and passed the test had better nutrition knowledge and were more physically active; these learnings have applications in improving training and test outcomes for cadets in the coming years.

Study: Physical strength, body composition, and G-test results of air force cadets based on nutrition knowledge differences. Image Credit: John Hoffman/Shutterstock.com

Background

Research in sports nutrition and training has applications in military training and nutritional management to maintain optimal physical and mental functioning while preventing disease. This requires an interdisciplinary approach that includes exercise, rest, recovery, and diet.

Soldiers in the Air Force work under extreme physiological stress in aerial environments, where they may suffer from hypoxia, hearing loss, flight illusion, cognitive dissonance, and gravity-induced loss of consciousness (G-LOC).

Enduring G-tests requires adequate nutrition and physical strength, but further understanding is required of how physical activity and strength can be improved among Air Force cadets.

About the study

Participants in the study were male senior cadets at the Air Force Academy in the Republic of Korea who took the G-test in 2022.

Those who were injured or unwilling to participate were excluded from the study. All sampled participants followed the same training, sleep, meal, and work schedules.

The G-test involved participants sitting in a cockpit-style seat of a high-speed centrifugal motion gondola for 30 seconds at an acceleration of 5 G.

Losing consciousness before 30 seconds meant failing the test. Based on their test results, participants were divided into those who passed the 30 s G-test (GP) and those who failed (GF).

Body strength was measured three months before the G-test, while body composition was assessed five days prior on an empty stomach. The strength test included a three-kilometer run, sit-ups, and push-ups.

Participants were asked to avoid high-intensity activities and sleep sufficiently on the previous day. Measures taken included skeletal muscle mass, body fat percentage, body fat mass, body mass index, height, and weight.

Participants also completed questionnaires assessing their physical activity levels and knowledge of nutrition-related topics. The data were analyzed using independent sample t-tests and logistic regressions at a significance level of 5%.

Findings

Of the 105 male cadets who participated in the study, those who passed the G-test weighed, on average, 3.5 kg more than those who failed and had a slightly higher BMI (24.05 compared to 23.08 on average).

Skeletal muscle mass, though higher in the GP group, was not significantly different. Similarly, GP cadets had lower body fat mass and body fat ratio, but the difference was not significant.

Cadets who passed were more physically active, working out for 22.2 minutes daily and 1.1 more reps each week on average. However, they did not perform significantly better in the physical strength evaluation.

Cadets in the GP group performed significantly better in the general nutrition knowledge questionnaire, with an overall score of 6.6 points higher on average.

The logistic regression showed significantly higher results for two sections (daily recommendation and food group) out of the four in the test questionnaire.

There were no significant differences for the sections on healthy food choices and diet, disease, and weight associations.

Conclusions

Cadets who passed the G-test were significantly different in terms of their weight and BMI, with indications that higher skeletal muscle mass and lower body fat mass may be beneficial during the test.

Specifically, higher muscle mass may facilitate better blood supply to the brain and prevent cadets from losing consciousness during the G-test. This indicates the need for a program design that balances aerobic and muscle training.

The GP cadets were also more physically active and more knowledgeable on nutrition-related topics.

While their food intake, energy metabolic rate, and activity were not measured, and how this knowledge translates into practice could not be observed, previous research indicates that people who understand nutrition benefits make more informed health decisions in terms of dietary intake. The authors recommend the introduction of a nutrition education program at the academy to address this.

The findings indicate that nutritional knowledge and overall physical condition promote better performance at an acceleration equivalent to five times that of the Earth’s gravitational pull.

In addition to continuous technological research, systematic nutrition management and education can improve and maintain optimal body composition, improving health outcomes under extreme physiological stress in aerial environments.

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February 12, 2024
Targeting gene-fibroblast interaction offers hope for treatment-resistant colon cancer

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A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 16, Issue 2, entitled, “PROX1 interaction with α-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance.”

The tumor microenvironment (TME) plays a vital role in tumor progression through intricate molecular interactions. Cancer-associated fibroblasts (CAFs), notably those expressing alpha-smooth muscle actin (α-SMA) or myofibroblasts, are instrumental in this context and correlate with unfavorable outcomes in colorectal cancer (CRC). While several transcription factors influence TME, the exact regulator causing CAF dysregulation in CRC remains elusive. Prospero Homeobox 1 (PROX1) stands out, as its inhibition reduces α-SMA-rich CAF activity. However, the therapeutic role of PROX1 is debated due to inconsistent study findings.

In this new study, researchers Shiue-Wei Lai, Yi-Chiao Cheng, Kee-Thai Kiu, Min-Hsuan Yen, Ying-Wei Chen, Vijesh Kumar Yadav, Chi-Tai Yeh, Kuang-Tai Kuo, and Tung-Cheng Chang from Taipei’s National Defense Medical Center, Taipei Medical University, Taipei Medical University Shuang-Ho Hospital, and National Taitung University used the ULCAN portal and noted an elevated PROX1 level in advanced colon adenocarcinoma, linking to a poor prognosis. Their assays determined the impact of PROX1 overexpression on CRC cell properties, while co-culture experiments spotlighted the PROX1-CAF relationship. Molecular expressions were validated by qRT-PCR and Western blots, with in vivo studies further solidifying the observations.

“Our study emphasized the connection between PROX1 and α-SMA in CAFs.”

Elevated PROX1 in CRC samples correlated with increased α-SMA in tumors. PROX1 modulation influenced the behavior of specific CRC cells, with its overexpression fostering invasiveness. Kaplan-Meier evaluations demonstrated a link between PROX1 or α-SMA and survival outcomes. Consequently, PROX1, alone or with α-SMA, emerges as a CRC prognostic marker. Co-culture and animal experiments further highlighted this relationship.

PROX1 appears crucial in modulating CRC behavior and therapeutic resistance within the TME by influencing CAFs, signifying the combined PROX1/α-SMA gene as a potential CRC prognostic marker. The concept of developing inhibitors targeting this gene set emerges as a prospective therapeutic strategy. However, this study is bound by limitations, including potential challenges in clinical translation, a focused exploration on PROX1/α-SMA potentially overlooking other significant molecular contributors, and the preliminary nature of the inhibitor development proposition.

“As we advance in this field, the development and clinical validation of small-molecule inhibitors targeting PROX1/α-SMA become imperative, paving the way to refine and optimize CRC therapeutic interventions.”

Source:

Journal reference:

Lai, S.-W., et al. (2024). PROX1 interaction with α-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance. Aging. doi.org/10.18632/aging.205447.

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February 8, 2024
Running helps to prevent weight or fat gain in the long-term, study shows

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Recently, some media outlets have highlighted that it is a myth that running will help you lose weight/fat. There is certainly convincing scientific evidence that after an initial loss in fat mass from engaging in an exercise regime, the body lowers its overall energy expenditure to conserve energy and ultimately its fat mass stores. This is nature’s insurance policy developed by our ancestors to prevent starvation during times of restricted food availability. A new study, however, showed that running prevents increases in body fat in the long-term.

Don’t be discouraged if, after a promising start, you can’t get your weight down by running. Recent work from the University of Jyväskylä, Finland, (https://jyx.jyu.fi/handle/123456789/91853#) has shown that running helps to prevent weight or fat gain in those that continue to run. Hopefully this helps to maintain motivation throughout the up-coming months once the fast gains have waned.

Our data clearly shows that lifelong running exercise, be it long-distance or repeated short-distance sprinting, maintains lower fat mass levels than a typical physically active lifestyle and also more than participating in competitive strength sports.”

Dr. Simon Walker, a Docent in Exercise Physiology, Faculty of Sport and Health Sciences, University of Jyväskylä

The older sprinters and endurance athletes in the study even had lower fat mass than young strength athletes and physically active controls.

“Absolutely this result motivates me to continue running. I’d certainly be happy with a fat percentage of 16-18% when I’m in my 70s and 80s”, continues Dr. Walker.

Lifelong strength training is best for maintaining muscle mass

The same study showed that individuals participating in lifelong resistance training maintained muscle mass better than those competing in sprint and long-distance running sports. Additionally, the older strength trainers had a similar amount of muscle mass as their young counterparts.

Dr. Walker suggests a combined training approach may be most beneficial for optimizing body composition throughout the lifespan:

“In terms of enhancing body composition through both heightened muscle mass and maintenance of a non-health affecting fat mass, it seems that a combined approach is recommendable. We know that both tissues, fat and muscle, influence overall health and function opposingly. Therefore, the best strategy would be to optimize both.

Walker suggests that two-to-three sessions of endurance and the same for resistance exercise (i.e. 4-6 sessions per week), depending on your preference, mood, motivation, or taking into account seasonal variation should lead to the same kinds of results seen in the athletes in the study.

“The key is perhaps to prevent a rise in fat mass or loss in muscle mass in the first place and maintain exercise throughout the lifespan. Thus, lifelong engagement in regular exercise does help to maintain a healthy body composition. That is no myth.”

The present study was performed using data from larger cohort studies (ATHLAS and CALEX-family cohorts) led by Dr. Marko Korhonen and Emer. Prof. Sulin Cheng, respectively. It includes males aged 20-39 and 70-89 years who were competitive sprinters, endurance runners and strength athletes, and also controls who were physically active but did not compete in sports.

“While we studied males only, I see no reason why our results would not be applicable for females too, especially considering the effects of menopause and other age-related effects.”

Source:

University of Jyväskylä

Journal reference:

Walker, S., et al. (2023). Body composition in male lifelong trained strength, sprint and endurance athletes and healthy age-matched controls. Frontiers in Sports and Active Living. doi.org/10.3389/fspor.2023.1295906.

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February 6, 2024
CT scans may be better first step for evaluating chest pain

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Previous studies have found less than 40% of patients with stable chest pain undergoing invasive coronary angiography are found to have obstructive coronary artery disease. Recent randomized clinical trials have demonstrated a benefit to using computed tomography angiography (CTA) first in evaluation of these patients, and a new study being presented at the American College of Cardiology Cardiovascular Summit lends credence to this strategy, finding that CT was associated with a higher likelihood of revascularization compared to other imaging modalities or no testing.

Stable angina is a type of chest discomfort that occurs when the heart muscle needs more oxygen than usual-;such as during stress, exercise or cold weather-;but it’s not getting it, often due to blocked coronary arteries. Patients with stable angina are often treated with guideline-directed medical therapy and lifestyle changes but may also need a coronary revascularization procedure to restore adequate blood flow to resolve their symptoms.

Right now, when a patient presents to their primary care physician or cardiologist with symptoms suspicious for angina, they are commonly referred for additional testing.”

Markus Scherer, MD, Director of Cardiac CT and Structural Heart Imaging at Atrium Health-Sanger Heart & Vascular Institute and study’s senior author

Between October 2022 and June 2023, researchers at Atrium Health-Sanger Heart & Vascular Institute in Charlotte, North Carolina, assessed 786 patients who had no prior diagnosis of coronary artery disease and underwent elective invasive coronary angiography (ICA) for the evaluation of suspected angina. The pre-ICA testing strategies were: no noninvasive testing with direct referral to ICA (44%), stress echocardiogram (3%), stress myocardial perfusion imaging (15%), stress MRI (2%) and coronary CTA (36%). The study cohort had a mean age of 66 years, was 63% male, 37% female, 81% White, 13% Black, 1% Asian, 1% Hispanic and 1% other.

The researchers compared rates of subsequent revascularization between patients whose initial evaluation was coronary CTA versus stress testing or clinical judgement (no testing). The “CT first” strategy was associated with subsequent revascularization in 62% of patients compared to 34% for the combination of other modalities or direct ICA referral.

The 2021 AHA/ACC Guideline for the Evaluation and Diagnosis of Chest Pain suggests either non-invasive functional imaging or coronary CTA as the initial test without specifying a preference for one or the other.

According to the researchers, there are a multitude of reasons health systems don’t currently use a CT first approach, including the availability of high-quality CT scanners; availability of qualified cardiac CT interpreting physicians; and challenges in transitioning to a newer approach after decades of pre-established patterns (i.e. stress testing). Furthermore, a CT first approach is predominately advocated for patients with unestablished coronary artery disease and does not apply to all, as some patient factors may reduce the accuracy and utility of coronary CTA.

“While care must be individualized, for patients with unknown or unestablished coronary artery disease, the transition to a ‘CT first’ strategy should be a high priority for cardiovascular care providers,” Scherer said. “The non-invasive approach has a lower risk and cost than a diagnostic heart catheterization and, for the CT approach-;but not stress testing-;provides information on the absence, presence and extent of coronary atherosclerosis and whether or not there are high risk plaques as well as vessel blockages, which helps streamline patient management and risk reduction.”

Since coronary CTA is less expensive than both nuclear myocardial perfusion imaging and ICA, there is a direct cost saving to patients and third-party payers with the CT first approach, according to Scherer. From the perspective of a health system, the most financially efficient evaluation approach becomes more important during the transition to a value-oriented health care system.

According to the authors, the study demonstrates “real world” credence to the randomized trials showing similar benefits to a “CT first” strategy and should promote increased adoption of this strategy for the evaluation of patients with chest pain and an unestablished history of coronary artery disease.

“Cardiac catheterization labs are a capital and human resource intensive care environment. Using them for their maximum potential of treating disease, rather than diagnosing it, bring the highest yield for these resources to the health care system,” Scherer said.

The full results of the study and other studies will be presented at the ACC Cardiovascular Summit 2024 in Washington, on February 1-3, 2024. The ACC Cardiovascular Summit 2024 will examine innovative strategies and emerging trends in CV care, assess operational efficiencies to enhance the effectiveness of the CV service line, and adopt customizable approaches that support economic sustainability.

Source:

American College of Cardiology

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February 1, 2024