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EULAR CVD management guidance focuses on gout, lupus, vasculitis
New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).
“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).
EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).
The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.
The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:
Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.
Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.
Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.
Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.
Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.
Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.
As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.
Can EULAR’s recommendations be implemented in U.S. rheumatology practices?
“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”
“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”
When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.
“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”
Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.
“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.
“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.
“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”
Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.
“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.
“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”
Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.
A version of this article first appeared on Medscape.com.
New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).
“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).
EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).
The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.
The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:
Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.
Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.
Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.
Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.
Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.
Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.
As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.
Can EULAR’s recommendations be implemented in U.S. rheumatology practices?
“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”
“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”
When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.
“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”
Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.
“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.
“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.
“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”
Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.
“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.
“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”
Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.
A version of this article first appeared on Medscape.com.
New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).
“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).
EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).
The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.
The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:
Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.
Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.
Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.
Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.
Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.
Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.
As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.
Can EULAR’s recommendations be implemented in U.S. rheumatology practices?
“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”
“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”
When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.
“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”
Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.
“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.
“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.
“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”
Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.
“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.
“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”
Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Could the protective effect on heart disease of eating more veg be exaggerated?
Eating sufficient amounts of vegetables might be good for overall health, but surprising results from a study suggested that their inclusion in the diet might have little or no effect on the risk of developing cardiovascular disease (CVD).
An investigation, led by the Nuffield department of population health at the University of Oxford, found that They said their findings, published in the journal Frontiers in Nutrition might mean that advice on vegetable intake and heart disease in high-income countries should be reappraised.
However, leading experts commented that the findings confirmed that higher overall vegetable consumption did lower the risk of cardiovascular disease.
UK Biobank data
Boosting health through a diet rich in vegetables has been backed by a large body of evidence, with guidelines consistently recommending them as a valuable source of macronutrients and micronutrients, such as dietary fiber, vitamins, and phytochemicals. However, the research team, which included the Chinese University of Hong Kong and the University of Bristol, set out to probe the independent effects of cooked and raw vegetables on health outcomes. Previous epidemiological studies had demonstrated inconsistent findings, they said.
They based their research on 399,586 people with no history of angina, stroke, and myocardial infarction, who enrolled in the UK Biobank. Of those, 55.4% were women, and 90.9% were of White ethnicity. The average body mass index was 27.3.
Raw and cooked vegetables
From their enrollment questionnaire, the mean intake of vegetables was found to be 2.3 heaped tablespoons per day of raw vegetables, and 2.8 of cooked vegetables. During an average follow-up of 12.1 years, 4.5% of the participants went on to develop CVD.
There was an inverse association between incident CVD and total and raw vegetable intake, but not cooked vegetable intake. Those who ate the most vegetables – both cooked and raw – had a 10% lower incidence of CVD, compared with those who ate the least. However, whereas raw vegetable intake was associated with an 11% reduction in CVD for those who ate the most, compared with the least, no reduction was seen for cooked vegetables.
Consuming two or more heaped tablespoons each day of cooked and raw vegetables was associated with a lower risk of dying from CVD, but little evidence was seen that a higher intake increased protection further. Similarly, there was evidence of an inverse association of CVD mortality with raw vegetable intake.
Researcher Qi Feng, from the Nuffield department of population health, said: “Our large study did not find evidence for a protective effect of vegetable intake on the occurrence of CVD. Instead, our analyses show that the seemingly protective effect of vegetable intake against CVD risk is very likely to be accounted for by bias from residual confounding factors, related to differences in socioeconomic situation and lifestyle.”
Expert opinions
Some clinical specialists took issue with the interpretation of the findings.
Dr. Dipender Gill, BMBCh, PhD, National Institute for Health Research clinical lecturer at St George’s, University of London, told the Science Media Centre that: “Many of the considered confounders that were adjusted for may actually represent mediating mechanisms. For example, vegetable consumption may reduce cardiovascular risk by lowering blood pressure and bodyweight, and improving glycaemic control.
“By adjusting for such traits, the authors may inadvertently be negating some of the mechanisms by which vegetable consumption is exerting beneficial effects.”
Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics at King’s College London, said: “The conclusion that cooked vegetables may not be effective in reducing risk of cardiovascular disease may not be justified, especially as the group consuming the highest levels of vegetables were more likely to be receiving medication for high blood cholesterol and high blood pressure (i.e. this group was at higher risk of CVD), compared with those consuming the lowest intake.” He added: “These findings should not be taken to indicate that eating more vegetables has no benefit to health, especially cardiovascular health.”
Naveed Sattar, FMedSci, FRCPath, FRCPGlas, professor of metabolic medicine at the University of Glasgow, agreed. “In short, this paper should in no way change advice to eat at least five portions of fruit and vegetables a day,” he said. “Many living in the U.K. fall well short of this, sadly, and more needs to be done to encourage better intake of vegetables.
“In fact, I suspect we may have underestimated the importance of a healthy diet on health and disease in general.”
A version of this article first appeared on Medscape.com.
Eating sufficient amounts of vegetables might be good for overall health, but surprising results from a study suggested that their inclusion in the diet might have little or no effect on the risk of developing cardiovascular disease (CVD).
An investigation, led by the Nuffield department of population health at the University of Oxford, found that They said their findings, published in the journal Frontiers in Nutrition might mean that advice on vegetable intake and heart disease in high-income countries should be reappraised.
However, leading experts commented that the findings confirmed that higher overall vegetable consumption did lower the risk of cardiovascular disease.
UK Biobank data
Boosting health through a diet rich in vegetables has been backed by a large body of evidence, with guidelines consistently recommending them as a valuable source of macronutrients and micronutrients, such as dietary fiber, vitamins, and phytochemicals. However, the research team, which included the Chinese University of Hong Kong and the University of Bristol, set out to probe the independent effects of cooked and raw vegetables on health outcomes. Previous epidemiological studies had demonstrated inconsistent findings, they said.
They based their research on 399,586 people with no history of angina, stroke, and myocardial infarction, who enrolled in the UK Biobank. Of those, 55.4% were women, and 90.9% were of White ethnicity. The average body mass index was 27.3.
Raw and cooked vegetables
From their enrollment questionnaire, the mean intake of vegetables was found to be 2.3 heaped tablespoons per day of raw vegetables, and 2.8 of cooked vegetables. During an average follow-up of 12.1 years, 4.5% of the participants went on to develop CVD.
There was an inverse association between incident CVD and total and raw vegetable intake, but not cooked vegetable intake. Those who ate the most vegetables – both cooked and raw – had a 10% lower incidence of CVD, compared with those who ate the least. However, whereas raw vegetable intake was associated with an 11% reduction in CVD for those who ate the most, compared with the least, no reduction was seen for cooked vegetables.
Consuming two or more heaped tablespoons each day of cooked and raw vegetables was associated with a lower risk of dying from CVD, but little evidence was seen that a higher intake increased protection further. Similarly, there was evidence of an inverse association of CVD mortality with raw vegetable intake.
Researcher Qi Feng, from the Nuffield department of population health, said: “Our large study did not find evidence for a protective effect of vegetable intake on the occurrence of CVD. Instead, our analyses show that the seemingly protective effect of vegetable intake against CVD risk is very likely to be accounted for by bias from residual confounding factors, related to differences in socioeconomic situation and lifestyle.”
Expert opinions
Some clinical specialists took issue with the interpretation of the findings.
Dr. Dipender Gill, BMBCh, PhD, National Institute for Health Research clinical lecturer at St George’s, University of London, told the Science Media Centre that: “Many of the considered confounders that were adjusted for may actually represent mediating mechanisms. For example, vegetable consumption may reduce cardiovascular risk by lowering blood pressure and bodyweight, and improving glycaemic control.
“By adjusting for such traits, the authors may inadvertently be negating some of the mechanisms by which vegetable consumption is exerting beneficial effects.”
Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics at King’s College London, said: “The conclusion that cooked vegetables may not be effective in reducing risk of cardiovascular disease may not be justified, especially as the group consuming the highest levels of vegetables were more likely to be receiving medication for high blood cholesterol and high blood pressure (i.e. this group was at higher risk of CVD), compared with those consuming the lowest intake.” He added: “These findings should not be taken to indicate that eating more vegetables has no benefit to health, especially cardiovascular health.”
Naveed Sattar, FMedSci, FRCPath, FRCPGlas, professor of metabolic medicine at the University of Glasgow, agreed. “In short, this paper should in no way change advice to eat at least five portions of fruit and vegetables a day,” he said. “Many living in the U.K. fall well short of this, sadly, and more needs to be done to encourage better intake of vegetables.
“In fact, I suspect we may have underestimated the importance of a healthy diet on health and disease in general.”
A version of this article first appeared on Medscape.com.
Eating sufficient amounts of vegetables might be good for overall health, but surprising results from a study suggested that their inclusion in the diet might have little or no effect on the risk of developing cardiovascular disease (CVD).
An investigation, led by the Nuffield department of population health at the University of Oxford, found that They said their findings, published in the journal Frontiers in Nutrition might mean that advice on vegetable intake and heart disease in high-income countries should be reappraised.
However, leading experts commented that the findings confirmed that higher overall vegetable consumption did lower the risk of cardiovascular disease.
UK Biobank data
Boosting health through a diet rich in vegetables has been backed by a large body of evidence, with guidelines consistently recommending them as a valuable source of macronutrients and micronutrients, such as dietary fiber, vitamins, and phytochemicals. However, the research team, which included the Chinese University of Hong Kong and the University of Bristol, set out to probe the independent effects of cooked and raw vegetables on health outcomes. Previous epidemiological studies had demonstrated inconsistent findings, they said.
They based their research on 399,586 people with no history of angina, stroke, and myocardial infarction, who enrolled in the UK Biobank. Of those, 55.4% were women, and 90.9% were of White ethnicity. The average body mass index was 27.3.
Raw and cooked vegetables
From their enrollment questionnaire, the mean intake of vegetables was found to be 2.3 heaped tablespoons per day of raw vegetables, and 2.8 of cooked vegetables. During an average follow-up of 12.1 years, 4.5% of the participants went on to develop CVD.
There was an inverse association between incident CVD and total and raw vegetable intake, but not cooked vegetable intake. Those who ate the most vegetables – both cooked and raw – had a 10% lower incidence of CVD, compared with those who ate the least. However, whereas raw vegetable intake was associated with an 11% reduction in CVD for those who ate the most, compared with the least, no reduction was seen for cooked vegetables.
Consuming two or more heaped tablespoons each day of cooked and raw vegetables was associated with a lower risk of dying from CVD, but little evidence was seen that a higher intake increased protection further. Similarly, there was evidence of an inverse association of CVD mortality with raw vegetable intake.
Researcher Qi Feng, from the Nuffield department of population health, said: “Our large study did not find evidence for a protective effect of vegetable intake on the occurrence of CVD. Instead, our analyses show that the seemingly protective effect of vegetable intake against CVD risk is very likely to be accounted for by bias from residual confounding factors, related to differences in socioeconomic situation and lifestyle.”
Expert opinions
Some clinical specialists took issue with the interpretation of the findings.
Dr. Dipender Gill, BMBCh, PhD, National Institute for Health Research clinical lecturer at St George’s, University of London, told the Science Media Centre that: “Many of the considered confounders that were adjusted for may actually represent mediating mechanisms. For example, vegetable consumption may reduce cardiovascular risk by lowering blood pressure and bodyweight, and improving glycaemic control.
“By adjusting for such traits, the authors may inadvertently be negating some of the mechanisms by which vegetable consumption is exerting beneficial effects.”
Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics at King’s College London, said: “The conclusion that cooked vegetables may not be effective in reducing risk of cardiovascular disease may not be justified, especially as the group consuming the highest levels of vegetables were more likely to be receiving medication for high blood cholesterol and high blood pressure (i.e. this group was at higher risk of CVD), compared with those consuming the lowest intake.” He added: “These findings should not be taken to indicate that eating more vegetables has no benefit to health, especially cardiovascular health.”
Naveed Sattar, FMedSci, FRCPath, FRCPGlas, professor of metabolic medicine at the University of Glasgow, agreed. “In short, this paper should in no way change advice to eat at least five portions of fruit and vegetables a day,” he said. “Many living in the U.K. fall well short of this, sadly, and more needs to be done to encourage better intake of vegetables.
“In fact, I suspect we may have underestimated the importance of a healthy diet on health and disease in general.”
A version of this article first appeared on Medscape.com.
FROM FRONTIERS IN NUTRITION
Your heart doesn’t like peas any more than you do
Big Vegetable has lied to us all
Hear this, children of the world: Your parents have betrayed you. They tell you day in and day out that vegetables are necessary, that they’re healthy, that you need them, but it is not the truth. Behind their foul taste is nothing but empty lies.
Okay, before we get a full-blown child rebellion on our hands, let’s reel things in. Eating vegetables has many benefits, and will help prevent many nasty medical conditions, such as diabetes or cancer. However, cardiovascular disease is not among them.
For their study published in Frontiers in Nutrition, researchers analyzed the diet, lifestyle, and medical history of nearly 400,000 U.K. adults over a 5-year period, finding that 4.5% developed heart disease and that the average adult consumed about 5 tablespoons of vegetables per day. Those who consumed the most vegetables had a reduction in heart disease incidence of about 15%, compared with those who ate the least.
Hang on, you’re thinking, we just said that vegetables didn’t prevent cardiovascular disease. But the data show otherwise! Ah, but the data are unadjusted. Once the researchers took socioeconomic status, information level, and general lifestyle into account, that benefit disappeared almost completely. The benefit seems to come not from the vegetables themselves, but from being able to afford better food and medical care in general.
The researchers were quick to note the other benefits of eating vegetables, and that people should probably keep eating those five servings a day. But we’re onto you, scientists. You can’t fool us with your vegetable-based lies. Unless we’re talking about pizza. Pizza is the best vegetable.
The good old days of surgery?
Modern surgical instruments, techniques, and technological innovations are amazing. It’s hard to imagine what surgery was like before laparoscopes came along, or x-ray machines, or even anesthesia. But those days weren’t really that long ago. Modern anesthesia, after all, dates back to just 1846. We’ve got socks almost that old.
But suppose we go back even further … say 5,300 years. Older than the oldest sock. Scientists studying a funerary chamber in Burgos, Spain, which was built in the 4th millennium B.C., have come across what looks like “the first known radical mastoidectomy in the history of humankind,” Sonia Díaz-Navarro of the University of Valladolid (Spain) and associates wrote in Scientific Reports.
One of the skulls they uncovered shows signs of trepanation. “Despite the [evidence] of cut marks, it is difficult to conclude the type of tool used to remove the bone tissue, most likely a sharp instrument with a circular movement,” they investigators said.
What is clear, though, is that the patient survived the surgery, because there is evidence of bone regeneration at the surgical sites. Sites? “Based on the differences in bone remodelling between the two temporals, it appears that the procedure was first conducted on the right ear, due to an ear pathology sufficiently alarming to require an intervention, which this prehistoric woman survived,” they explained.
The same procedure was then performed on the left ear, “but whether this was performed shortly after the right ear, or several months or even years later can’t be concluded from the existing evidence,” IFL Science reported.
Located nearby was a small section of tree bark with some scratches on it. That, ladies and gentlemen, was the first prior authorization form.
I hate that song, with reason
Do you have a favorite song? You may have a million reasons for loving that song. And past research can tell you why. But it’s only in a recent study that researchers were able to tell you why you dislike a song. And you know the song we’re talking about.
Dislike breaks down into three major categories of rationale: subject-related reasons (how the song makes you feel emotionally and/or physically), object-related reasons (the lyrics or composition), and social reasons (do you relate to this?). Researchers at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, interviewed 21 participants and asked them to come up with a prepared list of music that they disliked and why they didn’t like it. And there was a lot that they didn’t like: 277 dislikes worth, to be exact.
“The most often mentioned type of dislike was musical style, followed by artist and genre,” senior author Julia Merrill explained on Eurekalert. Just over 40% of those rationales for not liking the music just had to do with the music itself, but 85% involved the music combined with one of the other categories.
Social reasoning played a big part in dislike. If the listener didn’t feel like a part of the target in-group for the music or the music didn’t have the same social values as those of the listener, it had an impact on dislike, they said.
But our dislike of certain types of music doesn’t just separate us from people in a negative way. Looking at the dislike of certain types of music helps us define our terms of having good taste, the researchers explained. Saying that one type of music is better than another can bring us closer with like-minded people and becomes a piece of how we identify ourselves. Cue the music snobs.
So if you can blast Barry Manilow but can’t bring yourself to play the Rolling Stones, there’s a reason for that. And if you love Aretha Franklin but not Frank Sinatra, there’s a reason for that, too. It’s all very personal. Just as music is meant to be.
Big Vegetable has lied to us all
Hear this, children of the world: Your parents have betrayed you. They tell you day in and day out that vegetables are necessary, that they’re healthy, that you need them, but it is not the truth. Behind their foul taste is nothing but empty lies.
Okay, before we get a full-blown child rebellion on our hands, let’s reel things in. Eating vegetables has many benefits, and will help prevent many nasty medical conditions, such as diabetes or cancer. However, cardiovascular disease is not among them.
For their study published in Frontiers in Nutrition, researchers analyzed the diet, lifestyle, and medical history of nearly 400,000 U.K. adults over a 5-year period, finding that 4.5% developed heart disease and that the average adult consumed about 5 tablespoons of vegetables per day. Those who consumed the most vegetables had a reduction in heart disease incidence of about 15%, compared with those who ate the least.
Hang on, you’re thinking, we just said that vegetables didn’t prevent cardiovascular disease. But the data show otherwise! Ah, but the data are unadjusted. Once the researchers took socioeconomic status, information level, and general lifestyle into account, that benefit disappeared almost completely. The benefit seems to come not from the vegetables themselves, but from being able to afford better food and medical care in general.
The researchers were quick to note the other benefits of eating vegetables, and that people should probably keep eating those five servings a day. But we’re onto you, scientists. You can’t fool us with your vegetable-based lies. Unless we’re talking about pizza. Pizza is the best vegetable.
The good old days of surgery?
Modern surgical instruments, techniques, and technological innovations are amazing. It’s hard to imagine what surgery was like before laparoscopes came along, or x-ray machines, or even anesthesia. But those days weren’t really that long ago. Modern anesthesia, after all, dates back to just 1846. We’ve got socks almost that old.
But suppose we go back even further … say 5,300 years. Older than the oldest sock. Scientists studying a funerary chamber in Burgos, Spain, which was built in the 4th millennium B.C., have come across what looks like “the first known radical mastoidectomy in the history of humankind,” Sonia Díaz-Navarro of the University of Valladolid (Spain) and associates wrote in Scientific Reports.
One of the skulls they uncovered shows signs of trepanation. “Despite the [evidence] of cut marks, it is difficult to conclude the type of tool used to remove the bone tissue, most likely a sharp instrument with a circular movement,” they investigators said.
What is clear, though, is that the patient survived the surgery, because there is evidence of bone regeneration at the surgical sites. Sites? “Based on the differences in bone remodelling between the two temporals, it appears that the procedure was first conducted on the right ear, due to an ear pathology sufficiently alarming to require an intervention, which this prehistoric woman survived,” they explained.
The same procedure was then performed on the left ear, “but whether this was performed shortly after the right ear, or several months or even years later can’t be concluded from the existing evidence,” IFL Science reported.
Located nearby was a small section of tree bark with some scratches on it. That, ladies and gentlemen, was the first prior authorization form.
I hate that song, with reason
Do you have a favorite song? You may have a million reasons for loving that song. And past research can tell you why. But it’s only in a recent study that researchers were able to tell you why you dislike a song. And you know the song we’re talking about.
Dislike breaks down into three major categories of rationale: subject-related reasons (how the song makes you feel emotionally and/or physically), object-related reasons (the lyrics or composition), and social reasons (do you relate to this?). Researchers at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, interviewed 21 participants and asked them to come up with a prepared list of music that they disliked and why they didn’t like it. And there was a lot that they didn’t like: 277 dislikes worth, to be exact.
“The most often mentioned type of dislike was musical style, followed by artist and genre,” senior author Julia Merrill explained on Eurekalert. Just over 40% of those rationales for not liking the music just had to do with the music itself, but 85% involved the music combined with one of the other categories.
Social reasoning played a big part in dislike. If the listener didn’t feel like a part of the target in-group for the music or the music didn’t have the same social values as those of the listener, it had an impact on dislike, they said.
But our dislike of certain types of music doesn’t just separate us from people in a negative way. Looking at the dislike of certain types of music helps us define our terms of having good taste, the researchers explained. Saying that one type of music is better than another can bring us closer with like-minded people and becomes a piece of how we identify ourselves. Cue the music snobs.
So if you can blast Barry Manilow but can’t bring yourself to play the Rolling Stones, there’s a reason for that. And if you love Aretha Franklin but not Frank Sinatra, there’s a reason for that, too. It’s all very personal. Just as music is meant to be.
Big Vegetable has lied to us all
Hear this, children of the world: Your parents have betrayed you. They tell you day in and day out that vegetables are necessary, that they’re healthy, that you need them, but it is not the truth. Behind their foul taste is nothing but empty lies.
Okay, before we get a full-blown child rebellion on our hands, let’s reel things in. Eating vegetables has many benefits, and will help prevent many nasty medical conditions, such as diabetes or cancer. However, cardiovascular disease is not among them.
For their study published in Frontiers in Nutrition, researchers analyzed the diet, lifestyle, and medical history of nearly 400,000 U.K. adults over a 5-year period, finding that 4.5% developed heart disease and that the average adult consumed about 5 tablespoons of vegetables per day. Those who consumed the most vegetables had a reduction in heart disease incidence of about 15%, compared with those who ate the least.
Hang on, you’re thinking, we just said that vegetables didn’t prevent cardiovascular disease. But the data show otherwise! Ah, but the data are unadjusted. Once the researchers took socioeconomic status, information level, and general lifestyle into account, that benefit disappeared almost completely. The benefit seems to come not from the vegetables themselves, but from being able to afford better food and medical care in general.
The researchers were quick to note the other benefits of eating vegetables, and that people should probably keep eating those five servings a day. But we’re onto you, scientists. You can’t fool us with your vegetable-based lies. Unless we’re talking about pizza. Pizza is the best vegetable.
The good old days of surgery?
Modern surgical instruments, techniques, and technological innovations are amazing. It’s hard to imagine what surgery was like before laparoscopes came along, or x-ray machines, or even anesthesia. But those days weren’t really that long ago. Modern anesthesia, after all, dates back to just 1846. We’ve got socks almost that old.
But suppose we go back even further … say 5,300 years. Older than the oldest sock. Scientists studying a funerary chamber in Burgos, Spain, which was built in the 4th millennium B.C., have come across what looks like “the first known radical mastoidectomy in the history of humankind,” Sonia Díaz-Navarro of the University of Valladolid (Spain) and associates wrote in Scientific Reports.
One of the skulls they uncovered shows signs of trepanation. “Despite the [evidence] of cut marks, it is difficult to conclude the type of tool used to remove the bone tissue, most likely a sharp instrument with a circular movement,” they investigators said.
What is clear, though, is that the patient survived the surgery, because there is evidence of bone regeneration at the surgical sites. Sites? “Based on the differences in bone remodelling between the two temporals, it appears that the procedure was first conducted on the right ear, due to an ear pathology sufficiently alarming to require an intervention, which this prehistoric woman survived,” they explained.
The same procedure was then performed on the left ear, “but whether this was performed shortly after the right ear, or several months or even years later can’t be concluded from the existing evidence,” IFL Science reported.
Located nearby was a small section of tree bark with some scratches on it. That, ladies and gentlemen, was the first prior authorization form.
I hate that song, with reason
Do you have a favorite song? You may have a million reasons for loving that song. And past research can tell you why. But it’s only in a recent study that researchers were able to tell you why you dislike a song. And you know the song we’re talking about.
Dislike breaks down into three major categories of rationale: subject-related reasons (how the song makes you feel emotionally and/or physically), object-related reasons (the lyrics or composition), and social reasons (do you relate to this?). Researchers at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, interviewed 21 participants and asked them to come up with a prepared list of music that they disliked and why they didn’t like it. And there was a lot that they didn’t like: 277 dislikes worth, to be exact.
“The most often mentioned type of dislike was musical style, followed by artist and genre,” senior author Julia Merrill explained on Eurekalert. Just over 40% of those rationales for not liking the music just had to do with the music itself, but 85% involved the music combined with one of the other categories.
Social reasoning played a big part in dislike. If the listener didn’t feel like a part of the target in-group for the music or the music didn’t have the same social values as those of the listener, it had an impact on dislike, they said.
But our dislike of certain types of music doesn’t just separate us from people in a negative way. Looking at the dislike of certain types of music helps us define our terms of having good taste, the researchers explained. Saying that one type of music is better than another can bring us closer with like-minded people and becomes a piece of how we identify ourselves. Cue the music snobs.
So if you can blast Barry Manilow but can’t bring yourself to play the Rolling Stones, there’s a reason for that. And if you love Aretha Franklin but not Frank Sinatra, there’s a reason for that, too. It’s all very personal. Just as music is meant to be.
Robotic transcranial Doppler improves PFO detection after stroke
in a new study.
Being far easier to perform than regular transcranial Doppler ultrasound, it’s hoped that use of the robotic device will enable many more patients to undergo the more sensitive transcranial screening modality and increase the number of shunts identified.
“I believe robot-assisted transcranial Doppler ultrasound can fill the gap between the gold standard transcranial Doppler and transthoracic echocardiography, which is the current standard of care,” said lead author Mark Rubin, MD.
Dr. Rubin, who is assistant professor of neurology at University of Tennessee Health Science Center, Memphis, presented results of the BUBL study at the International Stroke Conference (ISC) 2022, where they were greeted with applause from the floor.
An improvement in the current standard of care
Dr. Rubin explained that patients with suspected embolic stroke are routinely screened for shunts in the heart, such as patent foramen ovale (PFO), that allow blood to flow from the right chamber to the left chamber and can lead to clots from the venous system, accessing the arterial system, then traveling to the brain and causing a stroke.
The current standard of care in screening for such shunts is the use of transthoracic echocardiography (TTE), a widely available and easy to perform, non-invasive procedure. “But we have known for decades that TTE does not pick up these shunts very well. With a sensitivity of only around 45%, it identifies less than half of the patients affected,” Dr. Rubin noted.
The more sensitive transesophageal echocardiography (TEE) gives much better results, but it is an invasive and unpleasant procedure with the ultrasound probe being passed down the throat, and the patient needing to be sedated, so it’s not appropriate for everyone, he noted.
“Transcranial Doppler ultrasound (TCD) also gives excellent results, with a sensitivity of about 96% for detecting PFO, but this procedure is difficult to perform and requires a great deal of skill in placing the probes in the right position and interpreting the signal,” Dr. Rubin said. “TCD has been around for decades, but it hasn’t caught on, as it is too difficult to do. It takes a lot of time to learn the technique.”
“With the robotic-assisted transcranial Doppler device, we can achieve the sensitivity of TCD without needing expert operators. This should vastly improve accessibility to this technology,” he said. “With such technology we can make significant strides into more accurate diagnoses on the cause of stroke, which should lead to better preventive treatments in those found to have right-to-left shunts.”
Robotic detection of shunts
For the BUBL study, the robotic TCD technique was compared with the standard TTE in 129 patients who had a diagnosis of presumed embolic stroke or transient ischemic attack (TIA), with all patients undergoing both procedures.
The robotic TCD device resembles a giant pair of headphones containing the ultrasound probes, which are attached to a frame. In the study, it was operated by a health care professional without TCD skills. Each ultrasound probe independently scans the temporal area autonomously – with angling and positive pressure against the scalp akin to a sonographer – to find and optimize bilateral middle cerebral artery signals, Dr. Rubin explained.
The primary endpoint was the detection of a right-to-left shunt. This occurred in 82 of the 129 patients (63.6%) with the robotic TCD device but in only 27 patients (20.9%) when TTE was used. This gives an absolute difference of 42.6% (95% confidence interval, 28.6%-56.7%; P < .001), which Dr. Rubin described as “astounding.”
However, he said he was not surprised by these results.
“In my experience with transcranial Doppler, I find shunts in patients every day that have not been seen with transthoracic echo,” he commented.
He noted that a previous meta-analysis has suggested a similar difference between TCD and transthoracic echo, but the current study provides prospectively collected data produced in a clinical trial setting and is therefore more reliable.
“What I hope comes from this is that more patients will be able to undergo transcranial Doppler, which is a far superior screening technique for identifying right-to-left shunts. There is so much evidence to support the use of transcranial Doppler, but with this new artificial-intelligence robotic device, we don’t need an expert to use it,” Dr. Rubin said.
He explained that finding a right-to-left shunt in stroke patients is particularly important, as it can direct treatment strategies to reduce future risk of recurrent strokes.
“If a patient has a large shunt, then they have a high risk of having another stroke, and the PFO should be closed.”
In this study, the robotic-assisted TCD detected three times as many large shunts that were considered “intervenable,” compared with transthoracic echo, identifying these shunts in 35 patients (27%) compared to just 13 (10%) with TTE.
“Of the 35 patients with intervenable shunts detected with robotic transcranial Doppler, TTE was completely negative in 18 of them and only suggested a small shunt in the others. So, the standard of care (TTE) missed half the patients with intervenable PFOs,” Dr. Rubin reported.
Study should ‘dramatically change’ practice
Commenting on the study, Patrick Lyden, MD, professor of physiology and neuroscience and of neurology, University of Southern California, Los Angeles, said: “Most clinicians hesitate to use transcranial Doppler given the need for specialized technical expertise to obtain a reliable result. This study showed that a robotic transcranial Doppler device – which can be applied by any cardiac non-invasive lab technician – provides reliable and rigorous data.”
He added: “This result will dramatically change the typical evaluation of patients with suspected PFO: In place of an invasive transesophageal echo that requires anesthesia and a cardiologist, most patients can have a non-invasive, robotic-guided transcranial Doppler and get the same diagnostic benefit.”
Dr. Lyden also pointed out that the cost of TCD is typically one-tenth that of TEE, although he said the cost of the robotic guided TCD “is not clear.”
A representative of the company that makes the robotic assisted device, NovaSignal, says the cost of the equipment is approximately $250,000, but “understanding the importance of the technology, we work with each hospital to meet their unique needs.”
The company adds that it currently has “over 45 commercial solutions deployed across 25 centers with 3-4 times growth expected year over year.”
The study was supported by NovaSignal, the company which makes the robotic device. Dr. Rubin reports acting as a consultant for the NovaSignal.
A version of this article first appeared on Medscape.com.
in a new study.
Being far easier to perform than regular transcranial Doppler ultrasound, it’s hoped that use of the robotic device will enable many more patients to undergo the more sensitive transcranial screening modality and increase the number of shunts identified.
“I believe robot-assisted transcranial Doppler ultrasound can fill the gap between the gold standard transcranial Doppler and transthoracic echocardiography, which is the current standard of care,” said lead author Mark Rubin, MD.
Dr. Rubin, who is assistant professor of neurology at University of Tennessee Health Science Center, Memphis, presented results of the BUBL study at the International Stroke Conference (ISC) 2022, where they were greeted with applause from the floor.
An improvement in the current standard of care
Dr. Rubin explained that patients with suspected embolic stroke are routinely screened for shunts in the heart, such as patent foramen ovale (PFO), that allow blood to flow from the right chamber to the left chamber and can lead to clots from the venous system, accessing the arterial system, then traveling to the brain and causing a stroke.
The current standard of care in screening for such shunts is the use of transthoracic echocardiography (TTE), a widely available and easy to perform, non-invasive procedure. “But we have known for decades that TTE does not pick up these shunts very well. With a sensitivity of only around 45%, it identifies less than half of the patients affected,” Dr. Rubin noted.
The more sensitive transesophageal echocardiography (TEE) gives much better results, but it is an invasive and unpleasant procedure with the ultrasound probe being passed down the throat, and the patient needing to be sedated, so it’s not appropriate for everyone, he noted.
“Transcranial Doppler ultrasound (TCD) also gives excellent results, with a sensitivity of about 96% for detecting PFO, but this procedure is difficult to perform and requires a great deal of skill in placing the probes in the right position and interpreting the signal,” Dr. Rubin said. “TCD has been around for decades, but it hasn’t caught on, as it is too difficult to do. It takes a lot of time to learn the technique.”
“With the robotic-assisted transcranial Doppler device, we can achieve the sensitivity of TCD without needing expert operators. This should vastly improve accessibility to this technology,” he said. “With such technology we can make significant strides into more accurate diagnoses on the cause of stroke, which should lead to better preventive treatments in those found to have right-to-left shunts.”
Robotic detection of shunts
For the BUBL study, the robotic TCD technique was compared with the standard TTE in 129 patients who had a diagnosis of presumed embolic stroke or transient ischemic attack (TIA), with all patients undergoing both procedures.
The robotic TCD device resembles a giant pair of headphones containing the ultrasound probes, which are attached to a frame. In the study, it was operated by a health care professional without TCD skills. Each ultrasound probe independently scans the temporal area autonomously – with angling and positive pressure against the scalp akin to a sonographer – to find and optimize bilateral middle cerebral artery signals, Dr. Rubin explained.
The primary endpoint was the detection of a right-to-left shunt. This occurred in 82 of the 129 patients (63.6%) with the robotic TCD device but in only 27 patients (20.9%) when TTE was used. This gives an absolute difference of 42.6% (95% confidence interval, 28.6%-56.7%; P < .001), which Dr. Rubin described as “astounding.”
However, he said he was not surprised by these results.
“In my experience with transcranial Doppler, I find shunts in patients every day that have not been seen with transthoracic echo,” he commented.
He noted that a previous meta-analysis has suggested a similar difference between TCD and transthoracic echo, but the current study provides prospectively collected data produced in a clinical trial setting and is therefore more reliable.
“What I hope comes from this is that more patients will be able to undergo transcranial Doppler, which is a far superior screening technique for identifying right-to-left shunts. There is so much evidence to support the use of transcranial Doppler, but with this new artificial-intelligence robotic device, we don’t need an expert to use it,” Dr. Rubin said.
He explained that finding a right-to-left shunt in stroke patients is particularly important, as it can direct treatment strategies to reduce future risk of recurrent strokes.
“If a patient has a large shunt, then they have a high risk of having another stroke, and the PFO should be closed.”
In this study, the robotic-assisted TCD detected three times as many large shunts that were considered “intervenable,” compared with transthoracic echo, identifying these shunts in 35 patients (27%) compared to just 13 (10%) with TTE.
“Of the 35 patients with intervenable shunts detected with robotic transcranial Doppler, TTE was completely negative in 18 of them and only suggested a small shunt in the others. So, the standard of care (TTE) missed half the patients with intervenable PFOs,” Dr. Rubin reported.
Study should ‘dramatically change’ practice
Commenting on the study, Patrick Lyden, MD, professor of physiology and neuroscience and of neurology, University of Southern California, Los Angeles, said: “Most clinicians hesitate to use transcranial Doppler given the need for specialized technical expertise to obtain a reliable result. This study showed that a robotic transcranial Doppler device – which can be applied by any cardiac non-invasive lab technician – provides reliable and rigorous data.”
He added: “This result will dramatically change the typical evaluation of patients with suspected PFO: In place of an invasive transesophageal echo that requires anesthesia and a cardiologist, most patients can have a non-invasive, robotic-guided transcranial Doppler and get the same diagnostic benefit.”
Dr. Lyden also pointed out that the cost of TCD is typically one-tenth that of TEE, although he said the cost of the robotic guided TCD “is not clear.”
A representative of the company that makes the robotic assisted device, NovaSignal, says the cost of the equipment is approximately $250,000, but “understanding the importance of the technology, we work with each hospital to meet their unique needs.”
The company adds that it currently has “over 45 commercial solutions deployed across 25 centers with 3-4 times growth expected year over year.”
The study was supported by NovaSignal, the company which makes the robotic device. Dr. Rubin reports acting as a consultant for the NovaSignal.
A version of this article first appeared on Medscape.com.
in a new study.
Being far easier to perform than regular transcranial Doppler ultrasound, it’s hoped that use of the robotic device will enable many more patients to undergo the more sensitive transcranial screening modality and increase the number of shunts identified.
“I believe robot-assisted transcranial Doppler ultrasound can fill the gap between the gold standard transcranial Doppler and transthoracic echocardiography, which is the current standard of care,” said lead author Mark Rubin, MD.
Dr. Rubin, who is assistant professor of neurology at University of Tennessee Health Science Center, Memphis, presented results of the BUBL study at the International Stroke Conference (ISC) 2022, where they were greeted with applause from the floor.
An improvement in the current standard of care
Dr. Rubin explained that patients with suspected embolic stroke are routinely screened for shunts in the heart, such as patent foramen ovale (PFO), that allow blood to flow from the right chamber to the left chamber and can lead to clots from the venous system, accessing the arterial system, then traveling to the brain and causing a stroke.
The current standard of care in screening for such shunts is the use of transthoracic echocardiography (TTE), a widely available and easy to perform, non-invasive procedure. “But we have known for decades that TTE does not pick up these shunts very well. With a sensitivity of only around 45%, it identifies less than half of the patients affected,” Dr. Rubin noted.
The more sensitive transesophageal echocardiography (TEE) gives much better results, but it is an invasive and unpleasant procedure with the ultrasound probe being passed down the throat, and the patient needing to be sedated, so it’s not appropriate for everyone, he noted.
“Transcranial Doppler ultrasound (TCD) also gives excellent results, with a sensitivity of about 96% for detecting PFO, but this procedure is difficult to perform and requires a great deal of skill in placing the probes in the right position and interpreting the signal,” Dr. Rubin said. “TCD has been around for decades, but it hasn’t caught on, as it is too difficult to do. It takes a lot of time to learn the technique.”
“With the robotic-assisted transcranial Doppler device, we can achieve the sensitivity of TCD without needing expert operators. This should vastly improve accessibility to this technology,” he said. “With such technology we can make significant strides into more accurate diagnoses on the cause of stroke, which should lead to better preventive treatments in those found to have right-to-left shunts.”
Robotic detection of shunts
For the BUBL study, the robotic TCD technique was compared with the standard TTE in 129 patients who had a diagnosis of presumed embolic stroke or transient ischemic attack (TIA), with all patients undergoing both procedures.
The robotic TCD device resembles a giant pair of headphones containing the ultrasound probes, which are attached to a frame. In the study, it was operated by a health care professional without TCD skills. Each ultrasound probe independently scans the temporal area autonomously – with angling and positive pressure against the scalp akin to a sonographer – to find and optimize bilateral middle cerebral artery signals, Dr. Rubin explained.
The primary endpoint was the detection of a right-to-left shunt. This occurred in 82 of the 129 patients (63.6%) with the robotic TCD device but in only 27 patients (20.9%) when TTE was used. This gives an absolute difference of 42.6% (95% confidence interval, 28.6%-56.7%; P < .001), which Dr. Rubin described as “astounding.”
However, he said he was not surprised by these results.
“In my experience with transcranial Doppler, I find shunts in patients every day that have not been seen with transthoracic echo,” he commented.
He noted that a previous meta-analysis has suggested a similar difference between TCD and transthoracic echo, but the current study provides prospectively collected data produced in a clinical trial setting and is therefore more reliable.
“What I hope comes from this is that more patients will be able to undergo transcranial Doppler, which is a far superior screening technique for identifying right-to-left shunts. There is so much evidence to support the use of transcranial Doppler, but with this new artificial-intelligence robotic device, we don’t need an expert to use it,” Dr. Rubin said.
He explained that finding a right-to-left shunt in stroke patients is particularly important, as it can direct treatment strategies to reduce future risk of recurrent strokes.
“If a patient has a large shunt, then they have a high risk of having another stroke, and the PFO should be closed.”
In this study, the robotic-assisted TCD detected three times as many large shunts that were considered “intervenable,” compared with transthoracic echo, identifying these shunts in 35 patients (27%) compared to just 13 (10%) with TTE.
“Of the 35 patients with intervenable shunts detected with robotic transcranial Doppler, TTE was completely negative in 18 of them and only suggested a small shunt in the others. So, the standard of care (TTE) missed half the patients with intervenable PFOs,” Dr. Rubin reported.
Study should ‘dramatically change’ practice
Commenting on the study, Patrick Lyden, MD, professor of physiology and neuroscience and of neurology, University of Southern California, Los Angeles, said: “Most clinicians hesitate to use transcranial Doppler given the need for specialized technical expertise to obtain a reliable result. This study showed that a robotic transcranial Doppler device – which can be applied by any cardiac non-invasive lab technician – provides reliable and rigorous data.”
He added: “This result will dramatically change the typical evaluation of patients with suspected PFO: In place of an invasive transesophageal echo that requires anesthesia and a cardiologist, most patients can have a non-invasive, robotic-guided transcranial Doppler and get the same diagnostic benefit.”
Dr. Lyden also pointed out that the cost of TCD is typically one-tenth that of TEE, although he said the cost of the robotic guided TCD “is not clear.”
A representative of the company that makes the robotic assisted device, NovaSignal, says the cost of the equipment is approximately $250,000, but “understanding the importance of the technology, we work with each hospital to meet their unique needs.”
The company adds that it currently has “over 45 commercial solutions deployed across 25 centers with 3-4 times growth expected year over year.”
The study was supported by NovaSignal, the company which makes the robotic device. Dr. Rubin reports acting as a consultant for the NovaSignal.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
USPSTF tweaks primary prevention statin recommendations in new draft guidance
Given the expansive contemporary role of statins for primary cardiovascular disease (CVD) prevention, the language in the new U.S. Preventive Services Task Force draft guidance on their use in that setting may seem conservative. Even so, the proposed recommendations, open to public comment until March 21, take more recent data into account but don’t substantially vary from the 2016 USPSTF document they are intended to replace.
The task force concluded “with moderate certainty” that a statin prescription will clinically benefit adults aged 40-75 years without CVD but with at least one of several risk factors, such as dyslipidemia or diabetes, who have a 10-year CVD risk of at least 7.5%.
the new report states. That, says an accompanying USPSTF press release, means such people “may benefit from statin use and should decide with their clinician if taking a statin is right for them.”
Also, notes the report, the net benefit of statin therapy is “at least moderate” for individuals with a 10% or greater CVD risk over the next decade who, the press release states, “should take a statin to prevent a first heart attack or stroke.”
The evidence review on which the task force based the guidance, the report says, lacked sufficient basis for determining statin benefit versus risk in adults older than 75 years without a history of CVD. “In the absence of this evidence, clinicians should use their judgment as to whether to offer a statin to a patient in this age group,” according to the press release.
The review focused on 22 clinical trials for data on the statin benefits and saw significantly decreased associated risks for death from any cause, fatal or nonfatal stroke, and fatal or nonfatal myocardial infarction with treatment. The combined trial populations exceeded 85,000 for assessing all-cause mortality and 76,000 for each of the other two endpoints.
To assess any potential statin therapy harms, the evidence review covered 19 clinical trials with a combined enrollment of about 75,000 – two more trials than considered in the 2016 document – plus three observational studies with more than 400,000 participants. Statins were found not to be associated with an increased risk for study withdrawal because of adverse events, nor were there signs of greater risk for myalgia or new-onset diabetes, compared with placebo.
“A majority of the trials reviewed by the USPSTF used moderate-intensity statin therapy,” the report states. “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”
A version of this article first appeared on Medscape.com.
Given the expansive contemporary role of statins for primary cardiovascular disease (CVD) prevention, the language in the new U.S. Preventive Services Task Force draft guidance on their use in that setting may seem conservative. Even so, the proposed recommendations, open to public comment until March 21, take more recent data into account but don’t substantially vary from the 2016 USPSTF document they are intended to replace.
The task force concluded “with moderate certainty” that a statin prescription will clinically benefit adults aged 40-75 years without CVD but with at least one of several risk factors, such as dyslipidemia or diabetes, who have a 10-year CVD risk of at least 7.5%.
the new report states. That, says an accompanying USPSTF press release, means such people “may benefit from statin use and should decide with their clinician if taking a statin is right for them.”
Also, notes the report, the net benefit of statin therapy is “at least moderate” for individuals with a 10% or greater CVD risk over the next decade who, the press release states, “should take a statin to prevent a first heart attack or stroke.”
The evidence review on which the task force based the guidance, the report says, lacked sufficient basis for determining statin benefit versus risk in adults older than 75 years without a history of CVD. “In the absence of this evidence, clinicians should use their judgment as to whether to offer a statin to a patient in this age group,” according to the press release.
The review focused on 22 clinical trials for data on the statin benefits and saw significantly decreased associated risks for death from any cause, fatal or nonfatal stroke, and fatal or nonfatal myocardial infarction with treatment. The combined trial populations exceeded 85,000 for assessing all-cause mortality and 76,000 for each of the other two endpoints.
To assess any potential statin therapy harms, the evidence review covered 19 clinical trials with a combined enrollment of about 75,000 – two more trials than considered in the 2016 document – plus three observational studies with more than 400,000 participants. Statins were found not to be associated with an increased risk for study withdrawal because of adverse events, nor were there signs of greater risk for myalgia or new-onset diabetes, compared with placebo.
“A majority of the trials reviewed by the USPSTF used moderate-intensity statin therapy,” the report states. “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”
A version of this article first appeared on Medscape.com.
Given the expansive contemporary role of statins for primary cardiovascular disease (CVD) prevention, the language in the new U.S. Preventive Services Task Force draft guidance on their use in that setting may seem conservative. Even so, the proposed recommendations, open to public comment until March 21, take more recent data into account but don’t substantially vary from the 2016 USPSTF document they are intended to replace.
The task force concluded “with moderate certainty” that a statin prescription will clinically benefit adults aged 40-75 years without CVD but with at least one of several risk factors, such as dyslipidemia or diabetes, who have a 10-year CVD risk of at least 7.5%.
the new report states. That, says an accompanying USPSTF press release, means such people “may benefit from statin use and should decide with their clinician if taking a statin is right for them.”
Also, notes the report, the net benefit of statin therapy is “at least moderate” for individuals with a 10% or greater CVD risk over the next decade who, the press release states, “should take a statin to prevent a first heart attack or stroke.”
The evidence review on which the task force based the guidance, the report says, lacked sufficient basis for determining statin benefit versus risk in adults older than 75 years without a history of CVD. “In the absence of this evidence, clinicians should use their judgment as to whether to offer a statin to a patient in this age group,” according to the press release.
The review focused on 22 clinical trials for data on the statin benefits and saw significantly decreased associated risks for death from any cause, fatal or nonfatal stroke, and fatal or nonfatal myocardial infarction with treatment. The combined trial populations exceeded 85,000 for assessing all-cause mortality and 76,000 for each of the other two endpoints.
To assess any potential statin therapy harms, the evidence review covered 19 clinical trials with a combined enrollment of about 75,000 – two more trials than considered in the 2016 document – plus three observational studies with more than 400,000 participants. Statins were found not to be associated with an increased risk for study withdrawal because of adverse events, nor were there signs of greater risk for myalgia or new-onset diabetes, compared with placebo.
“A majority of the trials reviewed by the USPSTF used moderate-intensity statin therapy,” the report states. “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”
A version of this article first appeared on Medscape.com.
Liquid embolism of AVM tied to high cure rate
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new observational data suggest. In a prospective, real-world study of more than 100 patients, use of the Onyx system was associated with a cure rate of 86% for cAVMs smaller than 3 cm.
“Endovascular treatment using Onyx is able to achieve, on its own, a very efficient cure rate with a low morbidity and mortality rate,” said investigator Laurent Spelle, MD, PhD, professor of neuroradiology at Paris-Saclay University and chair of NEURI, the Brain Vascular Center, Bicêtre Hospital, also in Paris.
Dr. Spelle presented the findings at the International Stroke Conference sponsored by the American Heart Association.
Prospective, multicenter study
Currently, the main treatment options for cAVM are embolization, neurosurgery, and radiosurgery. The Onyx liquid system, one method of providing embolization, uses a biocompatible ethylene vinyl alcohol copolymer.
It has been used in Europe for 22 years as a curative treatment and as a treatment before radiosurgery or neurosurgery. In the United States, Onyx is indicated for presurgical and preradiotherapy treatment only.
For this analysis, the researchers conducted a prospective, multicenter study to evaluate the long-term safety and efficacy of Onyx for the embolization of cAVM as curative treatment or preoperative preparation.
They enrolled 165 patients in the nonrandomized, observational study, which was conducted at 15 hospitals in France. Eligible participants had an untreated cAVM.
Patients were assigned to one of three groups, according to the hospital’s standard of care. One group underwent embolization with Onyx as curative treatment, one received Onyx as preparation for neurosurgery, and one underwent embolization with Onyx as preparation for radiosurgery.
The study’s safety endpoints were device- and procedure-related serious adverse events at 1 month after each embolization. The efficacy endpoints were recovery at 12 months after the last embolization or neurosurgery, or at a minimum of 36 months after radiosurgery.
The researchers defined morbidity as a worsening of modified Rankin Scale score of 2 or more points for patients presenting with baseline mRS of 0 or 1, or a worsening of 1 or more points for patients with an mRS of 2 or greater at baseline. An independent clinical events committee and core laboratory adjudicated the results.
‘A fantastic result’
In all, 140 patients were prospectively included, and 212 embolization procedures were performed. The population’s mean age was 41.4 years, and 60% of participants were men. About 61% of patients presented with symptoms, the most common of which were progressive neurologic deficit (41.2%) and headache (36.5%).
Approximately 64% of the cAVMs were ruptured. Most (75.7%) were smaller than 3 cm, and the remainder were between 3 and 6 cm. Most patients (59.3%) did not have an aneurysm.
Eight (3.8%) adverse events were associated with the use of Onyx. The rate of procedure-related neurologic serious adverse events was 7.1% within 1 month post embolization. Three deaths occurred (2.1%), one of which was considered device or procedure related.
A total of 87 patients underwent embolization alone, 14 of whom did not complete the study (2 died, 5 were lost to follow-up, and 7 withdrew). Of the 73 who completed the study, 58 (79.5%) had complete occlusion and full recovery at last follow-up. An additional 6.8% had 99% occlusion.
In addition, 3.4% of the population had significant morbidity, and 18.4% presented at baseline with mRS scores of 3-5. Of the latter group, 81.3% had mRS scores of 0-2 at last visit.
Of 21 patients who underwent subsequent neurosurgery, 18 completed follow-up. Of this group, 94.4% had complete occlusion. Of 32 patients receiving subsequent radiosurgery, 54.8% had complete occlusion, which was “a little bit disappointing,” said Dr. Spelle.
Overall, most patients (92.9%) had improved or stable mRS score. The overall mortality rate was 2.9%, and the rate of significant morbidity was 4.3%.
The rate of improved or stable mRS score was 94.3% for patients who underwent embolization alone, 85.7% for patients who also underwent neurosurgery, and 93.75% for patients who also underwent radiosurgery.
The mortality rate was 3.4% for patients who underwent embolization alone, 4.8% for patients who also underwent neurosurgery, and 0% for patients who also underwent radiosurgery.
The rate of significant morbidity was 2.3% for patients who underwent embolization alone, 9.5% for those who also underwent neurosurgery, and 6.25% for those who also underwent radiosurgery.
“We knew that this treatment was very effective, but this effectiveness was only known in a limited number of centers with a very high level of expertise,” said Dr. Spelle. “We were very pleasantly surprised that a larger-scale, multicenter study conducted in 15 different hospitals in France could achieve such a fantastic result.”
The study sites, however, were all departments in university hospitals with great experience in endovascular treatment of cAVM, he added.
Effective in unruptured AVMs?
Commenting on the findings, Mitchell Elkind, MD, professor of neurology and epidemiology, Columbia University, New York, said: “Arteriovenous malformations remain a relatively uncommon but serious cerebrovascular disorder. Any additional tool in the armamentarium to treat these lesions is welcome.”
The study results are encouraging, said Dr. Elkind, who was not involved in the study. They suggest that Onyx embolization can play an important role in the care of these patients. The treatment is associated with “low morbidity and excellent efficacy, particularly in combination with other surgical and radiographic approaches.”
The lack of a direct comparison with alternative embolization materials is a limitation of the study, however. “It is hard to compare Onyx to other agents based on these results,” said Dr. Elkind.
“It is also notable that one-third of the patients in the study had unruptured AVMs, which at least in one randomized trial, ARUBA, were not clearly shown to benefit from an intervention at all,” he continued.
It would have been valuable for the researchers to stratify the study results by ruptured versus unruptured AVMs, Dr. Elkind said.
The study was funded by Medtronic. Dr. Spelle reported receiving honoraria from the company. Dr. Elkind disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
More evidence links MI to cognitive decline over time
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
new research suggests.
Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.
The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”
The study was presented during the International Stroke Conference sponsored by the American Heart Association.
Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.
The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study
About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.
They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.
The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”
This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.
The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.
The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.
The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.
As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.
After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.
However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.
Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).
Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.
She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”
The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.
The next research steps for Dr. Johansen and associates are to look at differences in race and sex.
Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.
MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.
“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”
In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
New MIS-C guidance addresses diagnostic challenges, cardiac care
Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.
Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.
However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
Update needed in wake of Omicron
“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.
“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.
“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.
“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”
Diagnostic evaluation
The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.
Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
MIS-C and Kawasaki disease phenotypes
Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.
Cardiac management
Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms.
MIS-C treatment
Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.
When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.
The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
COVID-19 and hyperinflammation
The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”
The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.
Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”
The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.
Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.
However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
Update needed in wake of Omicron
“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.
“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.
“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.
“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”
Diagnostic evaluation
The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.
Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
MIS-C and Kawasaki disease phenotypes
Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.
Cardiac management
Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms.
MIS-C treatment
Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.
When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.
The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
COVID-19 and hyperinflammation
The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”
The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.
Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”
The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.
Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.
However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
Update needed in wake of Omicron
“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.
“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.
“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.
“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”
Diagnostic evaluation
The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.
Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
MIS-C and Kawasaki disease phenotypes
Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.
Cardiac management
Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms.
MIS-C treatment
Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.
When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.
The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
COVID-19 and hyperinflammation
The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”
The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.
Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”
The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS AND RHEUMATOLOGY
Tenecteplase for stroke thrombolysis up to 24 hours?
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Mixed results for cardiologists in stroke thrombectomy
Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.
Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).
The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.
The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).
Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).
“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.
But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.
“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.
“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.
Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).
“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”
The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.
“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”
Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.
The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”
Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.
“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”
In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”
A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.
Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”
Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.
They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.
“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”
Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.
Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).
The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.
The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).
Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).
“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.
But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.
“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.
“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.
Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).
“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”
The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.
“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”
Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.
The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”
Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.
“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”
In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”
A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.
Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”
Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.
They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.
“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”
Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Outcomes were mixed among ischemic stroke patients with large vessel occlusion who underwent thrombectomy by an interventional cardiologist as part of a multidisciplinary stroke team, in a single-center, prospective study from Poland.
Results from the 2-year experience show mechanical thrombectomy took longer when carried out by interventional cardiologists than by vascular surgeons and neuroradiologists (120 minutes vs. 105 minutes; P = .020).
The procedures were also less likely to achieve angiographic success, defined as a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b or 3 (55.7% vs. 71.7%; P = .013), reported Krystian Wita, MD, PhD, Medical University of Silesia, Katowice, Poland, and colleagues.
The differences in duration and recanalization require further attention, they noted, and are related to a learning curve, more time dedicated to decision-making and, in some cases, needing a second opinion. Cardiologists performed 80 procedures compared with 116 for vascular surgeons and 52 for neuroradiologists, and treated twice as many patients with a previous stroke (13.9% vs. 6.5%).
Still, the interventional cardiologist- and noncardiologist-treated groups had similar functional independence at 3 months, defined by a modified Rankin Scale (mRS) score of 0 to 2 (44.4% vs. 54.8%; P = .275). Mortality was also similar at 3 months (31.3% vs. 28.0%; P = .595).
“This is the first analysis to prove the noninferiority of the cardiology services in the treatment of stroke with mechanical thrombectomy,” the authors reported in JACC: Cardiovascular Interventions.
But commenting for this news organization, J Mocco, MD, senior vice chair of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Health System, New York, said this study isn’t designed as a noninferiority trial, is “grossly underpowered,” and the comparator cohort is not a gold standard comparator cohort.
“More importantly, they show that the cardiologists got significantly worse technical results and took longer, and we know that technical outcomes and the time to treatment are the two strongest predictors of outcome, which completely correlates with the fact that patients had 11% worse outcomes overall,” he said.
“It’s dumbfounding to me that this has been presented as evidence [that] an interventional cardiologist should be performing thrombectomy,” added Dr. Mocco, president-elect of the Society of NeuroInterventional Surgery.
Dr. Wita and coauthor Andrzej Kulach, MD, PhD, also with the Medical University of Silesia, told this news organization that timing is critical in mechanical thrombectomy (MT) and the sooner it’s performed, the better. But it cannot be performed by just any interventional cardiologist (IC).
“The IC must be trained in the procedure and cooperate with the neurologist to get good results,” they said. “We would like to stress that it is not a procedure for any cath lab and any cardiologist on duty. A network of cardiologists trained in MT must be organized and the stroke teams developed for the local unit to make the strategy reasonable and safe.”
The study was conducted from 2019 to 2020 and to participate, interventional cardiologists had to have performed a minimum of 700 angioplasties and 1,500 coronary angiographies and undergone complex training in thrombectomy, including 14-day training in a reference center and certified courses on a phantom and an animal model. They were also experienced in carotid angioplasty and participated as the second operators in neurointerventions.
“Considering the cardiologists are acting here in a multidisciplinary team led by neurologists, the findings are not surprising,” Dr. Wita and Dr. Kulach said. “What was surprising, is a certain level of skepticism among neurologists when cardiologists are to be involved in the procedure. We hope the quality of cardiology services will help to get over it.”
Major thrombectomy trials such as PRAGUE-16 have supported a role for interventional cardiologists to help meet demand for stroke thrombectomy. Dr. Wita and Dr. Kulach said there’s a lack of trained neuroradiologists and developed infrastructure for thrombectomy, whereas there’s a sufficient network of catheterization laboratories and trained cardiologists who could be involved.
The take-home message from the study, they said, is to “use the existing infrastructure to optimize the treatment of stroke. Building one from the very beginning is more time and resources-consuming.”
Dr. Mocco said a physician’s training is not a factor in the pathway to neurointerventional expertise, as long as they’re willing to put in the appropriate amount of specialization and training.
“There’s no way this represents a turf war or the neurology community somehow protecting its space, which is often used as a distraction, just like the idea that there’s not enough people,” he said. “It’s just not the case. Neurointervention is the most multispecialty space that I’m aware of.”
In the United States, at least, the problem isn’t a lack of resources or people to provide the service, but in getting patients to the correct hospitals, Dr. Mocco said. “We don’t have regionalized stroke care in the United States for the most part, so patients go to any hospital that says they provide stroke care rather than necessarily being triaged to capable centers that can provide the care.”
A 2021 Medicare analysis by Dr. Mocco and colleagues found that higher physician and hospital stroke thrombectomy volumes were associated with lower inpatient mortality and better outcomes.
Efforts are underway to regionalize care and delivery of patients in Los Angeles County and New York City, for example, where ambulances preferentially take patients with suspected large vessel occlusion to thrombectomy-capable stroke centers certified by independent organizations, Dr. Mocco said. In New York, “they’ve shown it has improved outcomes.”
Estêvão Carvalho de Campos Martins, MD, Hospital de Força Aérea do Galeão, Rio de Janeiro, and Fernando Luiz de Melo Bernardi, MD, Hospital Regional do Oeste, Chapecó, Brazil, noted in an accompanying editorial that the observational study is “hypothesis-generating only” and that the disconnect between technical and clinical outcomes is due to a type II error of low power.
They suggest that collaboration between specialties will be “essential for defining the optimal training program, so that ICs can reach solid procedural results.
“The accumulated experience with virtual simulation-based training for stroke could act as an educational accelerator but should be inserted in a prespecified program,” the editorialists said. “How to train and how to insert ICs into [an] MT interdisciplinary team is the current debate; meanwhile ICs are here, and many of them already contributing.”
Dr. Mocco is the principal investigator on research trials funded by Stryker Neurovascular, Microvention, and Penumbra; and is an investor in Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai , Synchron, Radical, and Truvic. He serves, or has recently served, as a consultant for: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai , Perflow, and CVAid. Dr. Carvalho de Campos Martins and Dr. Luiz de Melo Bernardi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.